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  • 1.
    Akbari, Saba
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Electrical Engineering, Networked Embedded Systems.
    Bergman, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Swedish Institute of Space Physics, Uppsala Division.
    Voigt, Thiemo
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Electrical Engineering, Networked Embedded Systems.
    Fredriksson, Jesper
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Swedish Institute of Space Physics, Uppsala Division.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Feasibility of Communication Between Sensor Nodes On-board Spacecraft Using Multi Layer Insulation2023Conference paper (Refereed)
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  • 2.
    Akbari, Saba
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Electrical Engineering, Networked Embedded Systems.
    Voigt, Thiemo
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Electrical Engineering, Networked Embedded Systems.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Demo: Sensor Node Communication Through Conductive Mesh Placed on Cotton Knit Fabric2023Conference paper (Other academic)
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  • 3.
    Atif, Abdul Raouf
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Evaluation of Biological Biomaterial Properties using Microfluidic Systems2023Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Despite increased orthopedic biomaterial research activity over previous decades, relatively few novel biomaterials have made it to clinical use. This may partially be due to the inability of existing in vitro testing routines to sufficiently replicate the physiological environment, leading to potentially inaccurate assessments of a biomaterial’s therapeutic potential. To address this, mathematical modelling and microfluidic design principles were assessed as possible supportive strategies to better improve the informativity of in vitro testing approaches.

    Using principles of the Langmuir isotherm, a predictive computational model was constructed to capture the dynamics of protein and cell adhesion on a biomaterial surface, specifically on calcium-deficient hydroxyapatite, which is a synthetic biomaterial that is compositionally similar to the inorganic phase of the bone. The results demonstrated the success of the model at capturing the trends of the data, thereby indicating potential use as a predicative tool to assist with in vitro data interpretation.

    Furthermore, attempts were made to improve the in vitro environment towards better physiological relevancy via the introduction of microfluidics, which is method of precise fluid control in micron-sized channels. For instance, the use of microfluidics allows for cell culture under more tissue relevant length scales, as well as the provision of a continuous media flow, which facilitates nutrient delivery and activation of mechanosensitive pathways through shear stress. Through development of such “Biomaterial-on-chip” microfluidic platforms, a general increase in cell viability and proliferation was seen when cells were cultured under flow. The effect of flow on other parameters such as material-induced ionic exchange, immunogenicity and mechanotransduction was also tested using the platform. By the culmination of the thesis work, the Biomaterial-on-chip platform was designed with inherent  standardization, allowing for the in vitro testing of different biomaterials of varying shapes and properties under the same conditions in the same platform. All in all, the main conclusion from this thesis work is that cell response can largely differ depending on the chosen culture conditions, which therefore necessities careful consideration of environmental parameters prior to the start of an in vitro biomaterial evaluation study.

    List of papers
    1. Experimental Characterization and Mathematical Modeling of the Adsorption of Proteins and Cells on Biomimetic Hydroxyapatite
    Open this publication in new window or tab >>Experimental Characterization and Mathematical Modeling of the Adsorption of Proteins and Cells on Biomimetic Hydroxyapatite
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    2022 (English)In: ACS Omega, E-ISSN 2470-1343, Vol. 7, no 1, p. 908-920Article in journal (Refereed) Published
    Abstract [en]

    Biomaterial development is a long process consisting of multiple stages of design and evaluation within the context of both in vitro and in vivo testing. To streamline this process, mathematical and computational modeling displays potential as a tool for rapid biomaterial characterization, enabling the prediction of optimal physicochemical parameters. In this work, a Langmuir isotherm-based model was used to describe protein and cell adhesion on a biomimetic hydroxyapatite surface, both independently and in a one-way coupled system. The results indicated that increased protein surface coverage leads to improved cell adhesion and spread, with maximal protein coverage occurring within 48 h. In addition, the Langmuir model displayed a good fit with the experimental data. Overall, computational modeling is an exciting avenue that may lead to savings in terms of time and cost during the biomaterial development process.

    Place, publisher, year, edition, pages
    American Chemical Society (ACS), 2022
    National Category
    Biochemistry and Molecular Biology
    Identifiers
    urn:nbn:se:uu:diva-472217 (URN)10.1021/acsomega.1c05540 (DOI)000736553600001 ()35036755 (PubMedID)
    Funder
    Swedish Research Council Formas, 2016-00781Swedish Research Council, 2017-05051Swedish Research Council, 2014-5680Knut and Alice Wallenberg Foundation, 2016.0112Knut and Alice Wallenberg Foundation, 2016.0255Göran Gustafsson Foundation for promotion of scientific research at Uppala University and Royal Institute of Technology, GG 2126
    Available from: 2022-04-12 Created: 2022-04-12 Last updated: 2023-03-01Bibliographically approved
    2. PDMS leaching and its implications for on-chip studies focusing on bone regeneration applications
    Open this publication in new window or tab >>PDMS leaching and its implications for on-chip studies focusing on bone regeneration applications
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    2020 (English)In: Organs-on-a-Chip, ISSN 2666-1020, Vol. 2, article id 100004Article in journal (Refereed) Published
    Abstract [en]

    Polydimethylsiloxane (PDMS) is among the most widely used materials for organ-on-chip systems. Despite itsmultiple beneficial characteristics from an engineering point of view, there is a concern about the effect of PDMSon the cells cultured in such devices. The aim of this study was to enhance the understanding of the effect of PDMSon cellular behavior in a context relevant for on-chip studies. The focus was put on an indirect effect of PDMS,namely leaching of uncrosslinked oligomers, particularly for bone regeneration applications. PDMS-based chipswere prepared and analyzed for the potential release of PDMS oligomers within the microfluidic channel whenkept at different flow rates. Leaching of uncrosslinked oligomers from PDMS was quantified as silicon concen-tration by inductively coupled plasma - optical emission spectrometry and further confirmed by mass spec-trometry. Subsequently, PDMS-leached media, with a silicon concentration matching the on-chip experiment,were prepared to study cell proliferation and osteogenic differentiation of MC3T3-E1 pre-osteoblasts and humanmesenchymal stem cells. The silicon concentration initially detected in the media was inversely proportional tothe tested flow rates and decreased to control levels within 52 h. In addition, by curing the material overnightinstead of 2 h, regardless of the curing temperature (65 and 80 C), a large reduction in silicon concentration wasfound, indicating the importance of the PDMS curing parameters. Furthermore, it was shown that PDMS oligo-mers enhanced the differentiation of MC3T3-E1 pre-osteoblasts, this being a cell type dependent effect as nochanges in cell differentiation were observed for human mesenchymal stem cells. Overall, this study illustrates theimportance of optimization steps when using PDMS devices for biological studies, in particular PDMS curingconditions and extensive washing steps prior to an experiment.

    Place, publisher, year, edition, pages
    Elsevier, 2020
    Keywords
    PDMS, Organs-on-chip, Human mesenchymal stem cells, Osteoblasts, Silicon
    National Category
    Engineering and Technology
    Research subject
    Engineering Science with specialization in Microsystems Technology
    Identifiers
    urn:nbn:se:uu:diva-410262 (URN)10.1016/j.ooc.2020.100004 (DOI)
    Funder
    Swedish Research Council Formas, 2016-00781Swedish Research Council, 2017-05051Göran Gustafsson Foundation for Research in Natural Sciences and Medicine, 1841Knut and Alice Wallenberg Foundation, 2016-0112
    Available from: 2020-05-13 Created: 2020-05-13 Last updated: 2023-03-01Bibliographically approved
    3. A microfluidics-based method for culturing osteoblasts on biomimetic hydroxyapatite
    Open this publication in new window or tab >>A microfluidics-based method for culturing osteoblasts on biomimetic hydroxyapatite
    2021 (English)In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 127, p. 327-337Article in journal (Refereed) Published
    Abstract [en]

    The reliability of conventional cell culture studies to evaluate biomaterials is often questioned, as in vitro outcomes may contradict results obtained through in vivo assays. Microfluidics technology has the potential to reproduce complex physiological conditions by allowing for fine control of microscale features such as cell confinement and flow rate. Having a continuous flow during cell culture is especially advantageous for bioactive biomaterials such as calcium-deficient hydroxyapatite (HA), which may otherwise alter medium composition and jeopardize cell viability, potentially producing false negative results in vitro. In this work, HA was integrated into a microfluidics-based platform (HA-on-chip) and the effect of varied flow rates (2, 8 and 14 µl/min, corresponding to 0.002, 0.008 and 0.014 dyn/cm2, respectively) was evaluated. A HA sample placed in a well plate (HA-static) was included as a control. While substantial calcium depletion and phosphate release occurred in static conditions, the concentration of ions in HA-on-chip samples remained similar to those of fresh medium, particularly at higher flow rates. Pre-osteoblast-like cells (MC3T3-E1) exhibited a significantly higher degree of proliferation on HA-on-chip (8 μl/min flow rate) as compared to HA-static. However, cell differentiation, analysed by alkaline phosphatase (ALP) activity, showed low values in both conditions. This study indicates that cells respond differently when cultured on HA under flow compared to static conditions, which indicates the need for more physiologically relevant methods to increase the predictive value of in vitro studies used to evaluate biomaterials.

    Place, publisher, year, edition, pages
    Elsevier, 2021
    Keywords
    Calcium phosphate cement, Flow, In vitro, On-chip, Shear stress
    National Category
    Biomaterials Science
    Research subject
    Engineering Science with specialization in Microsystems Technology
    Identifiers
    urn:nbn:se:uu:diva-440443 (URN)10.1016/j.actbio.2021.03.046 (DOI)000653434900012 ()33785452 (PubMedID)
    Funder
    Swedish Research Council Formas, 2016-00781Swedish Research Council, 2017-05051Knut and Alice Wallenberg Foundation, 2016-0112Göran Gustafsson Foundation for Research in Natural Sciences and Medicine, 1841
    Available from: 2021-04-19 Created: 2021-04-19 Last updated: 2024-01-15Bibliographically approved
    4. A microfluidic-based approach to investigate the inflammatory response of macrophages to pristine and drug-loaded nanostructured hydroxyapatite
    Open this publication in new window or tab >>A microfluidic-based approach to investigate the inflammatory response of macrophages to pristine and drug-loaded nanostructured hydroxyapatite
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    2022 (English)In: Materials Today Bio, ISSN 2590-0064, Vol. 16, article id 100351Article in journal (Refereed) Published
    Abstract [en]

    The in vitro biological characterization of biomaterials is largely based on static cell cultures. However, for highly reactive biomaterials such as calcium-deficient hydroxyapatite (CDHA), this static environment has limitations. Drastic alterations in the ionic composition of the cell culture medium can negatively affect cell behavior, which can lead to misleading results or data that is difficult to interpret. This challenge could be addressed by a microfluidics-based approach (i.e. on-chip), which offers the opportunity to provide a continuous flow of cell culture medium and a potentially more physiologically relevant microenvironment. The aim of this work was to explore microfluidic technology for its potential to characterize CDHA, particularly in the context of inflammation. Two different CDHA substrates (chemically identical, but varying in microstructure) were integrated on-chip and subsequently evaluated. We demonstrated that the on-chip environment can avoid drastic ionic alterations and increase protein sorption, which was reflected in cell studies with RAW 264.7 macrophages. The cells grown on-chip showed a high cell viability and enhanced proliferation compared to cells maintained under static conditions. Whereas no clear differences in the secretion of tumor necrosis factor alpha (TNF-α) were found, variations in cell morphology suggested a more anti-inflammatory environment on-chip. In the second part of this study, the CDHA substrates were loaded with the drug Trolox. We showed that it is possible to characterize drug release on-chip and moreover demonstrated that Trolox affects the TNF-α secretion and morphology of RAW 264.7 ​cells. Overall, these results highlight the potential of microfluidics to evaluate (bioactive) biomaterials, both in pristine form and when drug-loaded. This is of particular interest for the latter case, as it allows the biological characterization and assessment of drug release to take place under the same dynamic in vitro environment.

    Place, publisher, year, edition, pages
    Elsevier, 2022
    Keywords
    Biomaterial, Calcium phosphate cement, Drug release, In vitro, Macrophage, On-chip
    National Category
    Biophysics
    Research subject
    Engineering Science with specialization in Biomedical Engineering
    Identifiers
    urn:nbn:se:uu:diva-480694 (URN)10.1016/j.mtbio.2022.100351 (DOI)000843464200005 ()35865408 (PubMedID)
    Funder
    Swedish Research Council, 2017–05051Magnus Bergvall Foundation, 2020–03659Knut and Alice Wallenberg Foundation, 2016–0112Göran Gustafsson Foundation for Research in Natural Sciences and Medicine, 2126
    Available from: 2022-07-16 Created: 2022-07-16 Last updated: 2023-10-31Bibliographically approved
    5. Universal Biomaterial-on-Chip: A modular platform for flexible biomaterial integration and versatile quantitative assessment
    Open this publication in new window or tab >>Universal Biomaterial-on-Chip: A modular platform for flexible biomaterial integration and versatile quantitative assessment
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    A requirement for clinical approval is verification of a biomaterial’s functionality and biocompatibility. However, discrepancies between in vitro and in vivo evaluations have been reported, possibly due in part to a lack of physiological relevance of typical in vitro culture set-ups. We introduce a Universal Biomaterial-on-Chip (UBoC), which is a microfluidics device that allows integration of biomaterials with varied shapes and properties and subsequent evaluation of in vitro performance under design considerations that resemble physiological conditions. In addition, UBoC operates with multifunctional modalities such as continuous perfusion, shear stress mechanostimulation and cell co-culture. The device is constructed using simple 3D printing and microfabrication techniques and its cell culture area resembles a 96-well plate (0.32 cm2). Successful cell adhesion and proliferation was observed on-chip on different materials (hydroxyapatite, titanium and fibrin) using fluorescence microscopy. Furthermore, device applicability for mechanostimulation was demonstrated through shear stimulation, where sensitivity of pre-osteoblasts to flow was captured via live Ca2+ imaging. Finally, the modularity of the UBoC platform for on-chip co-culture experiments was established after simple modifications of on-board fluidic arrangements. Overall, the UBoC presents a useful tool that augments existing in vitro testing strategies and enables thorough comparisons between biomaterials in tunable culture conditions.

    Keywords
    Biomaterials, Calcium imaging, Mechanobiology, Microfluidics, Standardization, 3D printing
    National Category
    Medical Biotechnology
    Research subject
    Engineering Science with specialization in Biomedical Engineering
    Identifiers
    urn:nbn:se:uu:diva-497277 (URN)
    Funder
    Swedish Research Council, 2017-05051Göran Gustafsson Foundation for promotion of scientific research at Uppala University and Royal Institute of Technology, 2021-2126Magnus Bergvall Foundation, 2020-03659Knut and Alice Wallenberg Foundation, 2016-0112
    Available from: 2023-02-27 Created: 2023-02-27 Last updated: 2023-03-01
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    UUThesis_Atif,R-2023
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  • 4.
    Atif, Abdul Raouf
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Aramesh, Morteza
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering.
    Carter, Sarah-Sophia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mestres, Gemma
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Universal Biomaterial-on-Chip: A modular platform for flexible biomaterial integration and versatile quantitative assessmentManuscript (preprint) (Other academic)
    Abstract [en]

    A requirement for clinical approval is verification of a biomaterial’s functionality and biocompatibility. However, discrepancies between in vitro and in vivo evaluations have been reported, possibly due in part to a lack of physiological relevance of typical in vitro culture set-ups. We introduce a Universal Biomaterial-on-Chip (UBoC), which is a microfluidics device that allows integration of biomaterials with varied shapes and properties and subsequent evaluation of in vitro performance under design considerations that resemble physiological conditions. In addition, UBoC operates with multifunctional modalities such as continuous perfusion, shear stress mechanostimulation and cell co-culture. The device is constructed using simple 3D printing and microfabrication techniques and its cell culture area resembles a 96-well plate (0.32 cm2). Successful cell adhesion and proliferation was observed on-chip on different materials (hydroxyapatite, titanium and fibrin) using fluorescence microscopy. Furthermore, device applicability for mechanostimulation was demonstrated through shear stimulation, where sensitivity of pre-osteoblasts to flow was captured via live Ca2+ imaging. Finally, the modularity of the UBoC platform for on-chip co-culture experiments was established after simple modifications of on-board fluidic arrangements. Overall, the UBoC presents a useful tool that augments existing in vitro testing strategies and enables thorough comparisons between biomaterials in tunable culture conditions.

  • 5.
    Atif, Abdul Raouf
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lacis, Ugis
    Department of Engineering Mechanics, KTH.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bagheri, Shervin
    Department of Engineering Mechanics, KTH.
    Mestres, Gemma
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Modelling adsorption of proteins and cells on biomimetic hydroxyapatite2021Conference paper (Other academic)
    Abstract [en]

    Calcium-deficient hydroxyapatite (CDHA), a biomaterial similar to the inorganic bone matrix, can be used in non-load bearing areas to promote bone regeneration. Upon implantation, CDHA is exposed to blood, leading to serum protein deposition on the surface and enabling cell attachment via membrane-bound receptors. In cell culture studies, biomaterials are often pre-incubated in serum supplemented medium to mimic this process. In this work, to study the extent the protein layer assists in cell adhesion, a Langmuir isotherm-based model for protein and cell adhesion kinetics was used. 

    Download full text (pdf)
    ESB 2021 Conference Poster
  • 6.
    Atif, Abdul Raouf
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pujari-Palmer, Michael
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Tenje, Maria
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Mestres, Gemma
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    A microfluidics-based method for culturing osteoblasts on biomimetic hydroxyapatite2021In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 127, p. 327-337Article in journal (Refereed)
    Abstract [en]

    The reliability of conventional cell culture studies to evaluate biomaterials is often questioned, as in vitro outcomes may contradict results obtained through in vivo assays. Microfluidics technology has the potential to reproduce complex physiological conditions by allowing for fine control of microscale features such as cell confinement and flow rate. Having a continuous flow during cell culture is especially advantageous for bioactive biomaterials such as calcium-deficient hydroxyapatite (HA), which may otherwise alter medium composition and jeopardize cell viability, potentially producing false negative results in vitro. In this work, HA was integrated into a microfluidics-based platform (HA-on-chip) and the effect of varied flow rates (2, 8 and 14 µl/min, corresponding to 0.002, 0.008 and 0.014 dyn/cm2, respectively) was evaluated. A HA sample placed in a well plate (HA-static) was included as a control. While substantial calcium depletion and phosphate release occurred in static conditions, the concentration of ions in HA-on-chip samples remained similar to those of fresh medium, particularly at higher flow rates. Pre-osteoblast-like cells (MC3T3-E1) exhibited a significantly higher degree of proliferation on HA-on-chip (8 μl/min flow rate) as compared to HA-static. However, cell differentiation, analysed by alkaline phosphatase (ALP) activity, showed low values in both conditions. This study indicates that cells respond differently when cultured on HA under flow compared to static conditions, which indicates the need for more physiologically relevant methods to increase the predictive value of in vitro studies used to evaluate biomaterials.

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    Supplementary section
  • 7.
    Atif, Abdul Raouf
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Pujari-Palmer, Michael
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Influence of flow in the adhesion and proliferation of cells on hydroxyapatite integrated in a microscale culture2021Conference paper (Other academic)
    Abstract [en]

    INTRODUCTION:

    Synthetic biomaterials, such as calcium phosphate cements (CPCs), are a promising alternative to autologous bone to enhance bone regeneration. Calcium-deficient hydroxyapatite (CDHA), the end-product of apatite cements, matches the inorganic phase of the bone and exhibits excellent biocompatibility in vivo [1]. However,  in vitro, CDHA uptakes calcium ions (Ca2+) from cell culture medium [2], causing detrimental effects on cell activity and function [3]. The aim of this work was to integrate CDHA into a microfluidic chip that provides continued culture medium supply, and to evaluate cell adhesion and proliferation as compared to standard well plates.

    METHODS:

    CDHA was integrated in a polydimethylsiloxane (PDMS)-glass microfluidic chip (CDHA-on-chip). PDMS was cured in a 3D-printed mould at 60°C for 2h. α-tricalcium phosphate was mixed with 2.5% w/v Na2HPO4(aq) (liquid-to-powder of 0.65 ml/g) and the CPC was cast within a PDMS pocket. The CPC was immersed in an aqueous solution at 37°C for 10 days to ensure full transformation to CDHA. Through plasma treatment, a glass slide was bonded to the PDMS holding the CDHA, thus forming a 0.5mm channel above the CDHA. CDHA samples were pre-incubated for 24h in minimum essential media (MEM) supplemented with 10% FBS and 1% penicillin-streptomycin (sMEM). Pre-osteoblasts (MC3T3-E1) were seeded at 50,000 cells/cm2 and after a cell adhesion period of 2h, flow was applied for 72h through the chip at different rates: 2, 8 and 14 μl/min. A static (0 μl/min) chip condition was included, where sMEM was manually replaced every 24h. CDHA discs (⌀=6mm, h=2mm) placed in a 96-well plate were used as a standard static control (200 μl sMEM replaced every 24h). At 6h and 72h, the cells were stained with a calcein, propidium iodide and Hoechst triple-stain to assess their adhesion and proliferation, respectively. In a separate experiment, sMEM was flown through the chips for 24h at the aforementioned flow rates, and Ca2+ concentration was quantified via inductively coupled plasma-optical emission spectroscopy (ICP-OES). As control, sMEM in contact with CDHA discs for 24h was evaluated.

    RESULTS:

    A larger number of cells adhered on the CDHA-on-chip under flow as opposed to both static CDHA-on-chip and CDHA disc in a well plate. Differences in cell adhesion between the flow conditions were negligible. Cell proliferation at 72h was significantly increased under flow compared to CDHA disc samples (Fig.1A). Static CDHA-on-chip showed almost no viable cells. 2 and 8 μl/min flow conditions showed the greatest cell counts, followed by the 14 μl/min flow condition. At higher flow rates, Ca2+ concentrations were closer to in fresh medium (Fig.1B)

    DISCUSSION & CONCLUSIONS:

    The static CDHA-on-chip and disc samples displayed a low degree of cell adhesion and proliferation, which seemed to indicate that ionic exchange led to detrimental cell behaviour. Cells displayed the greatest degree of adhesion and proliferation at a flow rate of 2 and 8 μl/min, probably due to more optimal Ca2+ concentrations. At 14 μl/min, the degree of cell adhesion and proliferation decreased, which could be ascribed to adverse effects of shear stress.

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  • 8.
    Atif, Abdul Raouf
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pujari-Palmer, Michael
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Quantitative evaluation of osteoblast proliferation and differentiation on a biomaterial in a microfluidic device2020Conference paper (Other academic)
    Abstract [en]

    Introduction

    Calcium phosphate cements (CPCs) are able to transform into calcium deficient hydroxyapatite (CDHA), whose crystal size and chemistry closely matches that of the inorganic phase of bone [1]. CDHA readily uptakes calcium ions, and releases phosphate, when immersed in synthetic solutions that mimic physiological fluids [1]. While CPCs are able to enhance bone regeneration in defect sites located in non-load bearing areas, the ionic imbalance that arises from dissolution may also have detrimental effects on cell behavior and function. The purpose of this study was to culture cells on CDHA embedded in a microfluidic chip, under flow, to sustain optimal ionic concentrations, and subsequently evaluate cell proliferation and differentiation.   

    Methods

    CPC was cast into a polydimethylsiloxane (PDMS) pocket (h = 0.8 mm) and then set in a 0.9 % NaCl(aq) solution at 37°C for 10 days leading to conversion into CDHA. The CDHA embedded in PDMS were dried and bonded to glass via oxygen plasma treatment, resulting in chips with a 0.5 mm deep channel above the CDHA. In parallel, CDHA discs (⌀ = 6 mm) were set in Teflon molds for the same period of time. The CDHA chips and discs were sterilized with ethanol and pre-incubated with cell culture media overnight. MC3T3-E1 pre-osteoblasts (50,000 cells/cm2) were seeded on the CDHA, and allowed to adhere for 2 h, before initiating a flow of 8 µl/min. Cell proliferation (indirectly measured as the cytosolic lactate dehydrogenase (LDH) enzyme of cells previously adhered to the material) and cell differentiation (alkaline phosphatase activity normalized by total amount of protein) were quantified on day 1, 5 and 10. On day 10, cells were stained with Calcein, Propidium iodide (live/dead assay) and Hoechst (nucleus), and were imaged via fluorescence microscopy.   

    Results

    The fabrication of the CDHA-on-chip was successful (Fig 1A). There was a faster increase of osteoblast growth on the CDHA-on-chip (under flow) than on discs (static conditions). Specifically, between day 5 and 10, cell number on-chip increased a two-fold as compared to the insignificant change on discs (Fig 1B). Cells on-chip were observed confluent at day 10 (Fig 1C) and seemed to differentiate over time (not shown).

    Conclusion

    The integrated hydroxyapatite platform is a potential alternative for standard in vitro analysis using well plates. Application of flow ameliorates media ionic imbalance, while also providing fresh nutrients and removing waste.

  • 9.
    Baasch, Thierry
    et al.
    Lund Univ, Dept Biomed Engn, S-22100 Lund, Sweden.
    Fornell, Anna
    Lund University.
    Johansson, Carl
    Lund Univ, Dept Biomed Engn, S-22100 Lund, Sweden.
    Nilsson, Johan
    Lund University.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab. Department of Materials Science and Engineering, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Binary acoustic particle trapping in glass capillaries2021Conference paper (Refereed)
  • 10.
    Berglund, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Investigation of a spinel-based refractory as a carrier for a steel melt temperature sensor2020Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This master thesis work explored the possibility to measure the temperature in a steel melt for a longer time. A thermocouple was embedded in a ceramic material based on spinel (MgAl2O4), chosen as a sensor. The ceramic material was evaluated with regard to chemical corrosion from slag, thermal shock, and resistivity. Finally, a functional test in a steel melt was done in Sandvik’s experiment furnace.

    The corrosion study was made with two ceramic materials, one with a large amount of alumina and the other with a large amount of spinel. The materials were synthesised from different raw materials, which were mixed and sintered at 1000°C and 1650°C. This process led to four materials that were tested against two types of slags, at a temperature of 1600°C for 2 hours. One of the slag types had a large amount of calcium oxide (CaO) and the other a mixture of calcium oxide and added fluorspar (CaF2). The study shows that the spinel-rich material can withstand the corrosive slag better than an alumina-rich material.

    The thermal shock test was done with the two kinds of ceramic materials that were sintered at the higher temperature of 1650°C. The materials were subjected to a cold shock with a temperature difference of 1080°C which decreased the flexural strength with about 90%.

    The electrical resistivity test was tested by coating platina wireswith two types of electric insulating layers of a dielectric pasteor a type of cement. These two layers increased the resistance between two embedded wires inside the spinel-rich material at temperatures below 1000°C.

    The final results from the temperature measurements showed that continuous monitoring of the temperature in molten steel can be achieved by the design of a thermocouple embedded into the spinelmaterial, in shapes of cylindrical lances. Two, essentially identical, sensor lances were immersed 10 cm deep into molten steel, through the corrosive slag line, and measured the temperature in a steel melt around 1500°C. One of the sensors measured temperaturesof 1100-1300°C for 18 minutes, the other sensor measured temperatures around 1400°C for 9 minutes.

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    fulltext
  • 11.
    Brattström, Rutger
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Tjockleksmätning av sprutbetong med RFID2020Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This project has studied if RFID technology can be used to measure the thickness of shotcrete applied to walls, such as in tunnel construction. An RFID tag can be placed on the wall before the shotcrete is applied. When the RFID reader contacts the tag through the shotcrete the loss in signal strength can be measured. The goal was to analyse how the loss in signal strength through the medium related to the thickness of the shotcrete.

     

    Several tests with RFID tags cast into shotcrete has been performed. The results show that shotcrete is far too inhomogeneous for the measurements to convey meaningful information about the thickness. RFID is not recommended to be used for measuring shotcrete thickness.

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    fulltext
  • 12.
    Bugurcu, Alan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology, Ångström Space Technology Centre (ÅSTC).
    Investigation on how additive manufacturing with post-processing can be used to realize micronozzles2022Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This is predominantly a qualitative study on the manufacturing of micronozzles with an additive manufacturing (AM) technique, namely the laser-powered powder bed fusion (PBF-LB). 

    Manufacturing of micronozzles with standard microelectromechanical system technology often results in 2.5-D or close to 3-D structures and does not yield a fully rotationally symmetric nozzle. For this reason, AM can be a better solution. However, the structures obtained with PBF-LB exhibit very rough surfaces which will impair the performance of the micronozzle. To improve the surface finish electropolishing was performed on the interior walls. 

    Given the shape and the scale of the components, uniformity of the polishing is a challenge, calling for an inventive electrode configuration and electrolyte feed solution. The approach was to integrate an electrode on the inside of the converging part of the nozzle, to serve as a cathode for the electropolishing, already in the process, and to make the nozzle itself the vital part of the fluidic system. 

    With this, titanium micronozzles were manufactured with throat diameters varying between 300 and 800 μm. With the resolution of the used AM technique, it was possible to integrate the internal electrode in the micronozzles with a designed throat diameter down to 600 μm. Below this, the anode, and cathode, sometimes made contact short-circuiting the cell. Profilometry showed a decrease of the average surface roughness (𝑅𝑅𝑎𝑎) with 15-60 % for the electropolished micronozzles. The Schlieren imaging showed an exhaust that followed the throat’s axial direction and also demonstrated pressure disks and, hence, a supersonic jet exhaust. This study has shown that AM is a viable choice for manufacturing of rotationally symmetric micronozzles, and that electropolishing could be used to decrease the surface roughness on their inside uniformly with the integration of a cathode. 

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  • 13.
    Cantoni, Federico
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Fabrication advances of microvasculature models on-chip2023Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Despite the technological advances of the last decades, drug development remains a lengthy and costly process with uncertainties still associated with the poor predictive power of the in vitro and animal models. To address this limitation, microphysiological systems have been introduced in an attempt to increase the biological relevance of in vitro devices. One of the current challenges in MPS is the integration of a vasculature network to sustain 3D cultures to closely mimic human physiology.  This thesis proposed a new strategy to recreate a more representative vasculature system directly on-chip. As a first step, the 2-photon polymerization was investigated as a 3D printing technique to recreate structures with cell-relevant feature size and resolution. Subsequently, the 2-photon polymerization 3D printing was combined with micromolding to recreate a multi-hydrogel vasculature network integrated on-chip for cell culture. The synergy of the two methods ensured the generation of a high-fidelity multi-hydrogel scaffold for cell co-culture. To preserve the delicate cell culture while still ensuring the sample manipulation for monitoring and analysis, a customized microphysiological system carrier with an integrated heating and perfusion system was also developed. Finally, the possibility of tuning the properties of the 3D-printed hydrogel by controlling the printing parameters was investigated to guide glioblastoma cells to a vascularized compartment. Overall, the thesis not only demonstrated the fabrication versatility of 2 photon polymerization for a vasculature model directly on-chip but also showed the benefits in integrating microphysiological systems on a carrier.

    List of papers
    1. Round-robin testing of commercial two-photon polymerization 3D printers
    Open this publication in new window or tab >>Round-robin testing of commercial two-photon polymerization 3D printers
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    2023 (English)In: Additive Manufacturing, ISSN 2214-8604, E-ISSN 2214-7810, Vol. 76, article id 103761Article in journal (Refereed) Published
    Abstract [en]

    Since its introduction in the 1980s, 3D printing has advanced as a versatile and reliable tool with applications in different fields. Among the available 3D printing techniques, two-photon polymerization is regarded as one of the most promising technologies for microscale printing due to its ability to combine a high printing fidelity down to submicron scale with free-form structure design. Recently, the technology has been enhanced through the implementation of faster laser scanning strategies, as well as the development of new photoresists. This paves the way for a wide range of applications, which has resulted in an increasing number of available commercial systems. This work aims to provide an overview of the technology capability by comparing three commercial systems in a round-robin test. To cover a wide range of applications, six test structures with distinct features were designed, covering various aspects of interest, from single material objects with sub-micron feature sizes up to multi-material millimeter-sized objects. Application-specific structures were printed to evaluate surface roughness and the stitching capability of the printers. Moreover, the ability to generate free-hanging structures and complex surfaces required for cell scaffolds and microfluidic platform fabrication was quantitatively investigated. Finally, the influence of the numerical aperture of the fabrication objective on the printing quality was assessed. All three printers successfully fabricated samples comprising various three-dimensional features and achieved submicron resolution and feature sizes, demonstrating the versatility and precision of two-photon polymerization direct laser writing. Our study will facilitate the understanding of the technology maturity level, while highlighting specific aspects that characterize each of the investigated systems.

    Place, publisher, year, edition, pages
    Elsevier, 2023
    Keywords
    Two-photon polymerization, Direct laser writing, 3D printing, Microfabrication
    National Category
    Manufacturing, Surface and Joining Technology
    Research subject
    Engineering Science with specialization in Microsystems Technology
    Identifiers
    urn:nbn:se:uu:diva-510171 (URN)10.1016/j.addma.2023.103761 (DOI)001072489600001 ()
    Funder
    EU, Horizon 2020, 757444Knut and Alice Wallenberg Foundation, 2016.0112Swedish Research Council, 2019-00207
    Available from: 2023-08-25 Created: 2023-08-25 Last updated: 2024-01-08Bibliographically approved
    2. A perfusable multi-hydrogel vasculature on-chip engineered by 2-photon 3D printing and scaffold molding to improve microfabrication fidelity in hydrogels
    Open this publication in new window or tab >>A perfusable multi-hydrogel vasculature on-chip engineered by 2-photon 3D printing and scaffold molding to improve microfabrication fidelity in hydrogels
    2024 (English)In: Advanced Materials Technologies, E-ISSN 2365-709X, Vol. 9, no 4Article in journal (Refereed) Published
    Abstract [en]

    Engineering vasculature networks in physiologically relevant hydrogelsrepresents a challenge in terms of both fabrication, due to the cell–bioinkinteractions, as well as the subsequent hydrogel-device interfacing. Here, anew cell-friendly fabrication strategy is presented to realize perfusablemulti-hydrogel vasculature models supporting co-culture integrated in amicrofluidic chip. The system comprises two different hydrogels to specificallysupport the growth and proliferation of two different cell types selected for thevessel model. First, the channels are printed in a gelatin-based ink bytwo-photon polymerization (2PP) inside the microfluidic device. Then, ahuman lung fibroblast-laden fibrin hydrogel is injected to surround the printednetwork. Finally, human endothelial cells are seeded inside the printedchannels. The printing parameters and fibrin composition are optimized toreduce hydrogel swelling and ensure a stable model that can be perfused withcell media. Fabricating the hydrogel structure in two steps ensures that nocells are exposed to cytotoxic fabrication processes, while still obtaining highfidelity printing. In this work, the possibility to guide the endothelial cellinvasion through the 3D printed scaffold and perfusion of the co-culturemodel for 10 days is successfully demonstrated on a custom-made perfusionsystem.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2024
    National Category
    Biomedical Laboratory Science/Technology
    Identifiers
    urn:nbn:se:uu:diva-510168 (URN)10.1002/admt.202300718 (DOI)001136245100001 ()
    Funder
    Knut and Alice Wallenberg Foundation, WAF 2016.0112EU, European Research Council, 757444
    Available from: 2023-08-24 Created: 2023-08-24 Last updated: 2024-05-22Bibliographically approved
    3. A microfluidic chip carrier including temperature control and perfusion system for long-term cell imaging
    Open this publication in new window or tab >>A microfluidic chip carrier including temperature control and perfusion system for long-term cell imaging
    Show others...
    2021 (English)In: HardwareX, E-ISSN 2468-0672, Vol. 10, p. e00245-, article id e00245Article in journal (Refereed) Published
    Abstract [en]

    Microfluidic devices are widely used for biomedical applications but there is still a lack of affordable, reliable and user-friendly systems for transferring microfluidic chips from an incubator to a microscope while maintaining physiological conditions when performing microscopy. The presented carrier represents a cost-effective option for sustaining environmental conditions of microfluidic chips in combination with minimizing the device manipulation required for reagent injection, media exchange or sample collection. The carrier, which has the outer dimension of a standard well plate size, contains an integrated perfusion system that can recirculate the media using piezo pumps, operated in either continuous or intermittent modes (50–1000 µl/min). Furthermore, a film resistive heater made from 37 µm-thick copper wires, including temperature feedback control, was used to maintain the microfluidic chip temperature at 37 °C when outside the incubator. The heater characterisation showed a uniform temperature distribution along the chip channel for perfusion flow rates up to 10 µl/min. To demonstrate the feasibility of our platform for long term cell culture monitoring, mouse brain endothelial cells (bEnd.3) were repeatedly monitored for a period of 10 days, demonstrating a system with both the versatility and the potential for long imaging in microphysiological system cell cultures.

    Place, publisher, year, edition, pages
    ElsevierElsevier BV, 2021
    Keywords
    Microphysiological system, long-term cell monitoring, functional assay on-chipPortable microfluidics
    National Category
    Biomedical Laboratory Science/Technology
    Research subject
    Engineering Science with specialization in Microsystems Technology
    Identifiers
    urn:nbn:se:uu:diva-463458 (URN)10.1016/j.ohx.2021.e00245 (DOI)000734418800003 ()
    Funder
    Knut and Alice Wallenberg Foundation, WAF 2016.0112EU, Horizon Europe, 812954EU, European Research Council, 757444
    Available from: 2022-01-10 Created: 2022-01-10 Last updated: 2024-01-15Bibliographically approved
    4. Microengineering a cell co-culture platform for glioblastoma cell migration and intravasation studies
    Open this publication in new window or tab >>Microengineering a cell co-culture platform for glioblastoma cell migration and intravasation studies
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Biomedical Laboratory Science/Technology
    Research subject
    Engineering Science with specialization in Biomedical Engineering
    Identifiers
    urn:nbn:se:uu:diva-510170 (URN)
    Available from: 2023-08-24 Created: 2023-08-24 Last updated: 2023-09-05
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  • 14.
    Cantoni, Federico
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Barbe, Laurent
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Pohlit, Hannah
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    A perfusable multi-hydrogel vasculature on-chip engineered by 2-photon 3D printing and scaffold molding to improve microfabrication fidelity in hydrogels2024In: Advanced Materials Technologies, E-ISSN 2365-709X, Vol. 9, no 4Article in journal (Refereed)
    Abstract [en]

    Engineering vasculature networks in physiologically relevant hydrogelsrepresents a challenge in terms of both fabrication, due to the cell–bioinkinteractions, as well as the subsequent hydrogel-device interfacing. Here, anew cell-friendly fabrication strategy is presented to realize perfusablemulti-hydrogel vasculature models supporting co-culture integrated in amicrofluidic chip. The system comprises two different hydrogels to specificallysupport the growth and proliferation of two different cell types selected for thevessel model. First, the channels are printed in a gelatin-based ink bytwo-photon polymerization (2PP) inside the microfluidic device. Then, ahuman lung fibroblast-laden fibrin hydrogel is injected to surround the printednetwork. Finally, human endothelial cells are seeded inside the printedchannels. The printing parameters and fibrin composition are optimized toreduce hydrogel swelling and ensure a stable model that can be perfused withcell media. Fabricating the hydrogel structure in two steps ensures that nocells are exposed to cytotoxic fabrication processes, while still obtaining highfidelity printing. In this work, the possibility to guide the endothelial cellinvasion through the 3D printed scaffold and perfusion of the co-culturemodel for 10 days is successfully demonstrated on a custom-made perfusionsystem.

    Download full text (pdf)
    fulltext
  • 15.
    Cantoni, Federico
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Barbe, Laurent
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Roy, Ananya
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wicher, Grzegorz K.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Forsberg Nilsson, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Microengineering a cell co-culture platform for glioblastoma cell migration and intravasation studiesManuscript (preprint) (Other academic)
  • 16.
    Cantoni, Federico
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Barbe, Laurent
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bunea, Ada-Iona
    DTU.
    2-photon polymerization–benchmarking commercial printers to access the nanometric scale in 3D printing2022Conference paper (Refereed)
  • 17.
    Cantoni, Federico
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pohlit, Hannah
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tenje, Maria
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Hydrogel membrane fabricated by 2-photon polymerization in a microfluidic chip for bio-interface investigations2020Conference paper (Other academic)
    Abstract [en]

    Current bio-interface models often rely upon a porous thin membrane integrated in a microfluidic system to combine the cell proximity with a precise delivery of biochemical and biophysical cues1. However, this strategy still fails to provide the cultured cells with a good mimic of the tissue physiology. Compared to a conventional porous membrane, a natural-sourced hydrogel represents a more suitable candidate to recapitulate the 3D environment of the biological counterpart2. The platform presented in this study includes a 200 µm thick methacrylated gelatin (GelMA) membrane fabricated with 2-photon polymerization3 in-between two microfluidic channels. 

  • 18.
    Cantoni, Federico
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering.
    Samanta, Ayan
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Methacryl modified gelatin hydrogels for co-culture of cells to mimic blood-brain barrier2018Conference paper (Other academic)
  • 19.
    Cantoni, Federico
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Werr, Gabriel
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Barbe, Laurent
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Porras, Ana Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    A microfluidic chip carrier including temperature control and perfusion system for long-term cell imaging2021In: HardwareX, E-ISSN 2468-0672, Vol. 10, p. e00245-, article id e00245Article in journal (Refereed)
    Abstract [en]

    Microfluidic devices are widely used for biomedical applications but there is still a lack of affordable, reliable and user-friendly systems for transferring microfluidic chips from an incubator to a microscope while maintaining physiological conditions when performing microscopy. The presented carrier represents a cost-effective option for sustaining environmental conditions of microfluidic chips in combination with minimizing the device manipulation required for reagent injection, media exchange or sample collection. The carrier, which has the outer dimension of a standard well plate size, contains an integrated perfusion system that can recirculate the media using piezo pumps, operated in either continuous or intermittent modes (50–1000 µl/min). Furthermore, a film resistive heater made from 37 µm-thick copper wires, including temperature feedback control, was used to maintain the microfluidic chip temperature at 37 °C when outside the incubator. The heater characterisation showed a uniform temperature distribution along the chip channel for perfusion flow rates up to 10 µl/min. To demonstrate the feasibility of our platform for long term cell culture monitoring, mouse brain endothelial cells (bEnd.3) were repeatedly monitored for a period of 10 days, demonstrating a system with both the versatility and the potential for long imaging in microphysiological system cell cultures.

    Download full text (pdf)
    fulltext
  • 20.
    Cantoni, Federico
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Werr, Gabriel
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Barbe, Laurent
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    A carrier with an integrated perfusion and heating systems for long-term imaging of microfluidic chips2021Conference paper (Refereed)
    Abstract [en]

    Microfluidic chips offer many benefits for cell studies, including an accurate spatial and temporal control over the growth conditions1. Despite the large expansion of microfluidics in biological applications2, there have been only a few developments of devices to simplify microfluidic chip handling and imaging. Here, we present a carrier of well-plate format with integrated cell media recirculation and heating systems to provide a stable environment for the cell culture during the imaging outside the incubator. Moreover, the absence of external tubing reduces the risk of contamination and bubble formation during the carrier transfers and reagent injections enabling long-term experiment monitoring. Our system was validated by repeatedly (day 1, 3, 7 and 10) taking the cultured mouse endothelial cells (bEnd.3) out of the incubator for imaging.

  • 21.
    Carter, Sarah-Sophia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Atif, Abdul Raouf
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Kadekar, Sandeep
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Lanekoff, Ingela
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Varghese, Oommen P.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    PDMS leaching and its implications for on-chip studies focusing on bone regeneration applications2020In: Organs-on-a-Chip, ISSN 2666-1020, Vol. 2, article id 100004Article in journal (Refereed)
    Abstract [en]

    Polydimethylsiloxane (PDMS) is among the most widely used materials for organ-on-chip systems. Despite itsmultiple beneficial characteristics from an engineering point of view, there is a concern about the effect of PDMSon the cells cultured in such devices. The aim of this study was to enhance the understanding of the effect of PDMSon cellular behavior in a context relevant for on-chip studies. The focus was put on an indirect effect of PDMS,namely leaching of uncrosslinked oligomers, particularly for bone regeneration applications. PDMS-based chipswere prepared and analyzed for the potential release of PDMS oligomers within the microfluidic channel whenkept at different flow rates. Leaching of uncrosslinked oligomers from PDMS was quantified as silicon concen-tration by inductively coupled plasma - optical emission spectrometry and further confirmed by mass spec-trometry. Subsequently, PDMS-leached media, with a silicon concentration matching the on-chip experiment,were prepared to study cell proliferation and osteogenic differentiation of MC3T3-E1 pre-osteoblasts and humanmesenchymal stem cells. The silicon concentration initially detected in the media was inversely proportional tothe tested flow rates and decreased to control levels within 52 h. In addition, by curing the material overnightinstead of 2 h, regardless of the curing temperature (65 and 80 C), a large reduction in silicon concentration wasfound, indicating the importance of the PDMS curing parameters. Furthermore, it was shown that PDMS oligo-mers enhanced the differentiation of MC3T3-E1 pre-osteoblasts, this being a cell type dependent effect as nochanges in cell differentiation were observed for human mesenchymal stem cells. Overall, this study illustrates theimportance of optimization steps when using PDMS devices for biological studies, in particular PDMS curingconditions and extensive washing steps prior to an experiment.

    Download full text (pdf)
    fulltext
  • 22.
    Carter, Sarah-Sophia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Atif, Abdul Raouf
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lanekoff, Ingela
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Tailoring the biocompatibility of the elastomer PDMS for on-chip applications2018Conference paper (Refereed)
  • 23.
    Carter, Sarah-Sophia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Barbe, Laurent
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Exploring microfluidics as a tool to evaluate the biological properties of a titanium alloy under dynamic conditions2020In: Biomaterials Science, ISSN 2047-4830, E-ISSN 2047-4849, Vol. 8, p. 6309-6321Article in journal (Refereed)
    Abstract [en]

    To bring novel biomaterials to clinical use, reliable in vitro models are imperative. The aim of this work was to develop a microfluidic tool to evaluate the biological properties of biomaterials for bone repair. Two approaches to embed medical grade titanium (Ti6Al4V) on-chip were explored. The first approach consisted of a polydimethylsiloxane microfluidic channel placed onto a titanium disc, held together by an additively manufactured fixture. In the second approach, a titanium disc was assembled onto a microscopic glass slide, using a double-sided tape microfluidic channel. Both approaches demonstrated potential for maintaining MC3T3-E1 preosteoblast-like cell cultures on-chip, as was shown by the vast majority of living cells after 1 day. In addition, the cells cultured on-chip showed a more elongated morphology compared to cells grown under static conditions and a tendency to align to the direction of the flow. For longer-term (i.e. 10 days) studies, the glass-based chip was selected. Assessment of cell viability showed a high number of living cells during the entire experimental period. Cell proliferation and differentiation studies revealed an increase in cell proliferation on-chip, suggesting that proliferation was the dominating process at the detriment of differentiation in this micrometric dynamic environment. These results illustrate the importance of optimizing in vitro cell culture conditions and how these may affect biomaterial testing outcomes. Overall, this work provides a step towards more in vivo-like microfluidic testing platforms, which are expected to provide more reliable in vitro screening of biomaterials.

    Download full text (pdf)
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  • 24.
    Carter, Sarah-Sophia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Barbe, Laurent
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tenje, Maria
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Mestres, Gemma
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    On-chip evaluation of the biological properties of medical-grade titanium2020Conference paper (Refereed)
    Abstract [en]

    On-chip evaluation of the biological properties of medical-grade titanium

    Sarah-Sophia D. Carter1, Laurent Barbe1, Maria Tenje1 and Gemma Mestres1,*

    1 Department of Materials Science and Engineering, Science for Life Laboratory, Uppsala University, Uppsala, Sweden

    *E-mail: gemma.mestres@angstrom.uu.se

    Introduction

    Before entering the clinic, biomaterials need to be thoroughly evaluated, which requires accurate in vitro models. However, it has been shown that the currently used models correlate poorly with in vivo results [1]. In this work, microfluidic chips that integrate medical grade titanium (Ti6Al4V) were fabricated and subsequently used to study the biological properties of this biomaterial on-chip. The overall goal of this project is to develop on-chip platforms to evaluate novel biomaterials for bone regeneration.

    Theory and Experimental procedure

    A glass coverslip (175 µm thick) was laser cut to fit a Ti6Al4V disc (⌀ = 12 mm) and assembled onto a microscopic glass slide (1 mm thick) using double-sided tape (140 µm thick), the latter shaping the microfluidic channel. To ensure a tight seal between the glass coverslip and the Ti6Al4V disc, a UV adhesive was used. MC3T3-E1 pre-osteoblast cells were seeded at 45,000 cells/cm2 and allowed to adhere for 4 hours prior to starting the perfusion. After 1, 5 and 10 days, cell proliferation and cell differentiation were evaluated by the lactate dehydrogenase (LDH) assay (used as an indirect method to quantify the cytosolic enzyme LDH of cells previously adhered to the biomaterial) and the alkaline phosphatase (ALP) assay. As a static control, MC3T3-E1 cells were seeded on Ti6Al4V discs in a well plate.

    Results and Discussion

    MC3T3-E1 cells were successfully grown on Ti6Al4V on-chip, as was confirmed by an increase in cell proliferation over time, which became significantly elevated compared to the static condition from day 5 onwards (Figure 1A). Cell differentiation increased over the studied period for both on-chip and static conditions (Figure 1B). However, in the static condition, ALP activity reached much higher levels compared to on-chip. All together, these results correlate well with the fact that cell proliferation is the dominating process on-chip during the experimental period.

    Conclusion

    Microfluidic chips that integrate medical grade Ti6Al4V were fabricated and used to evaluate the biological properties of this biomaterial under dynamic conditions. Cell proliferation and differentiation studies indicate that MC3T3-E1 cells cultured on Ti6Al4V on-chip remain in a proliferative state during the time period of 10 days.

    Acknowledgments

    GM acknowledges Formas, Vetenskapsrådet and Göran Gustafsson´s Foundation for financial support.

    References

    [1] G. Hulsart-Billström et al., European Cells and Materials 31, 312-322 (2016).

  • 25.
    Carter, Sarah-Sophia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nguyen, Hugo
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Moreira, Milena
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Medical grade titanium on-chip: assessing the biological properties of biomaterials for bone regeneration2019Conference paper (Other academic)
    Abstract [en]

    Medical grade titanium on-chip: assessing the biological properties of biomaterials for bone regeneration

     

    Sarah-Sophia D. Carter1, Hugo Nguyen2, Milena Moreira1, Maria Tenje1, and Gemma Mestres1

    1Department of Engineering Sciences, Science for Life Laboratory, Uppsala University, Sweden

    2Department of Engineering Sciences, Uppsala University, Sweden

     

    Introduction

    Before entering the clinic, biomaterials need to be thoroughly evaluated, which requires accurate in vitro models. In this work, we have developed a microfluidic device that could be used to assess the biological properties of biomaterials, in a more in vivo-like environment than what is currently possible.

     

    Methods

    Our device consists of a polydimethylsiloxane (PDMS, Sylgard 184) microfluidic channel (l= 6 mm, w= 2 mm, h= 200 µm) and a titanium disc (Ti6Al4V, at bottom), held together by an additively manufactured fixture (Fig. 1A). PDMS was cured overnight at 65°C on a silicon wafer master. Once the microchannel and titanium disc were positioned, MC3T3-E1 pre-osteoblast-like cells were seeded (50,000 cells/cm2). After 5 hours incubation under standard culture conditions, flow was started (2 μl/min). As a control, MC3T3-E1 cells were seeded onto plain titanium discs off-chip. Cell viability and morphology were assessed after 20 hours by calcein-AM/propidium iodide (PI), staining live and dead cells respectively.

     

    Results and discussion

    Figure 1B and 1C show calcein-AM/PI stained MC3T3-E1 cells cultured on-chip and figure 1D shows the control, MC3T3-E1 cells cultured off-chip. The potential to culture cells in our chip was confirmed by the presence of a majority of viable cells (green) with a similar morphology as the control sample. The reason for the increased amount of dead cells (red) on-chip compared to the control needs to be further examined, which requires longer-term experiments.

    Conclusion

    We have set the first steps towards a microfluidic tool for the assessment of biological properties of biomaterials.

  • 26.
    Cruz, Javier
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Microfluidics for High-Pressure Inertial Focusing: Focusing, Separation and Concentration of Micro and Sub-micron Particles2020Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The birth of microsystems set the ground for technologies never imagined before, for it is not only the small size what characterizes the miniaturized systems, but unique phenomena arise in the micro scale. This thesis relates to one such unique phenomenon, inertial focusing, a phenomenon that occurs in microfluidic systems if very special conditions are met and that allows for fine manipulation of particles in fluid samples. This ability is key in a bigger picture: the analysis of complex fluids, where rare particles of interest may be present in very few numbers amongst a myriad of others, making the task difficult – if not impossible. A system exploiting inertial focusing allows, for instance, to focus, separate, isolate and concentrate such rare particles of interest, and even to transfer them to another fluid, thereby enabling/facilitating their detection and analysis. Examples of rare particles of interest in complex fluids are circulating tumor cells in blood, that give away the presence of cancer, extracellular vesicles also in blood, that contain biomarkers with physiological and pathological information about the patient, or bacteria in natural water, where the species present and their numbers are to be monitored for safety reasons and/or biological studies. This thesis covers the state of art physical principles behind the phenomenon and extends the understanding both in theory and applications. Specifically, the technology is extended to allow for manipulation of sub-micron particles, a range of interest as it comprises bacteria, viruses and organelles of eukaryotic cells. This was possible by an analysis of the balance of forces in play and by the integration of inertial focusing in high-pressure systems (up to 200 bar). In a second block, a very special line of inertial focusing is introduced and developed; inertial focusing in High Aspect Ratio Curved (HARC) microfluidics. These systems, engineered to rearrange the force field responsible for the particle manipulation, not only achieve excellent performances for focusing and concentration of particles, but also extreme resolution in their separation (mathematically unlimited; demonstrated experimentally for differences in size down to 80 nm). Perhaps more important than the performance, the systems are stable, intuitive and simpler to design, attributes that we hope will make the technology and its outstanding benefits more accessible to the community. With its remarkable performance, it would not come as a surprise if, in the near future, inertial focusing makes a strong impact on how analyses are performed nowadays and opens up for possibilities beyond the current state of the art.

    List of papers
    1. High pressure inertial focusing for separating and concentrating bacteria at high throughput
    Open this publication in new window or tab >>High pressure inertial focusing for separating and concentrating bacteria at high throughput
    Show others...
    2017 (English)In: Journal of Micromechanics and Microengineering, ISSN 0960-1317, E-ISSN 1361-6439, Vol. 27, no 8, article id 084001Article in journal (Refereed) Published
    Abstract [en]

    Inertial focusing is a promising microfluidic technology for concentration and separation of particles by size. However, there is a strong correlation of increased pressure with decreased particle size. Theory and experimental results for larger particles were used to scale down the phenomenon and find the conditions that focus 1 mu m particles. High pressure experiments in robust glass chips were used to demonstrate the alignment. We show how the technique works for 1 mu m spherical polystyrene particles and for Escherichia coli, not being harmful for the bacteria at 50 mu l min(-1). The potential to focus bacteria, simplicity of use and high throughput make this technology interesting for healthcare applications, where concentration and purification of a sample may be required as an initial step.

    Place, publisher, year, edition, pages
    IOP PUBLISHING LTD, 2017
    Keywords
    bacteria separation, particle separation, inertial focusing, high pressure, glass chips, PDMS, microfluidic channel
    National Category
    Condensed Matter Physics Other Materials Engineering Analytical Chemistry Physical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-329919 (URN)10.1088/1361-6439/aa6b14 (DOI)000404540500001 ()
    Funder
    EU, Horizon 2020, 644669
    Available from: 2018-02-22 Created: 2018-02-22 Last updated: 2020-12-07Bibliographically approved
    2. Inertial focusing with sub-micron resolution for separation of bacteria
    Open this publication in new window or tab >>Inertial focusing with sub-micron resolution for separation of bacteria
    2019 (English)In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 19, no 7, p. 1257-1266Article in journal (Refereed) Published
    Abstract [en]

    In this paper, we study inertial focusing in curved channels and demonstrate the alignment of particles with diameters between 0.5 and 2.0 m, a range of biological relevance since it comprises a multitude of bacteria and organelles of eukaryotic cells. The devices offer very sensitive control over the equilibrium positions and allow two modes of operation. In the first, particles having a large variation in size are focused and concentrated together. In the second, the distribution spreads in a range of sizes achieving separation with sub-micron resolution. These systems were validated with three bacteria species (Escherichia coli, Salmonella typhimurium and Klebsiella pneumoniae) showing good alignment while maintaining the viability in all cases. The experiments also revealed that the particles follow a helicoidal trajectory to reach the equilibrium positions, similar to the fluid streamlines simulated in COMSOL, implying that these positions occupy different heights in the cross section. When the equilibrium positions move to the inner wall as the flow rate increases, they are at a similar distance from the centre than in straight channels (approximate to 0.6R), but when the equilibrium positions move to the outer wall as the flow rate increases, they are closer to the centre and the particles pass close to the inner wall to elevate their position before reaching them. These observations were used along with COMSOL simulations to explain the mechanism behind the local force balance and the migration of particles, which we believe contributes to further understanding of the phenomenon. Hopefully, this will make designing more intuitive and reduce the high pressure demands, enabling manipulation of particles much smaller than a micrometer.

    Place, publisher, year, edition, pages
    ROYAL SOC CHEMISTRY, 2019
    National Category
    Biochemistry and Molecular Biology
    Identifiers
    urn:nbn:se:uu:diva-382383 (URN)10.1039/c9lc00080a (DOI)000462723900009 ()30821308 (PubMedID)
    Funder
    EU, Horizon 2020, 644669
    Available from: 2019-04-25 Created: 2019-04-25 Last updated: 2020-12-07Bibliographically approved
    3. Stable 3D Inertial Focusing by High Aspect Ratio Curved Microfluidics
    Open this publication in new window or tab >>Stable 3D Inertial Focusing by High Aspect Ratio Curved Microfluidics
    2021 (English)In: Journal of Micromechanics and Microengineering, ISSN 0960-1317, E-ISSN 1361-6439, Vol. 31, article id 015008Article in journal (Refereed) Published
    Abstract [en]

    Fine manipulation of particles is essential for the analysis of complex samples such as blood or environmental water, where rare particles of interest may be masked by millions of others. Inertial focusing is amongst the most promising techniques for this task, enabling label-free manipulation of particles with sub-micron resolution at very high flow rates. However, the phenomenon still remains difficult to predict due to the focus position shifting in tortuous ways as function of the channel geometry, flow rate and particle size. Here, we present a new line of microfluidics that exploit inertial focusing in High Aspect Ratio Curved (HARC) microchannels and overcome this limitation. Consisting of a single curved channel, HARC systems provide a highly predictable, single focus position near the centre of the inner wall, largely independent of the flow rate and particle size.

    An explanation of the mechanism of migration and focus of particles, together with its governing equations, is provided based on simulations in COMSOL Multiphysics and experimental results. HARC microchannels built in silicon-glass were used for experimental validation, achieving a high quality, single focus position for a range of microparticles with sizes of 0.7 - 1 µm and bacterial cells (Escherichia coli). The recovery of 1 µm particles was 99.84% with a factor four in concentration.

    With a stable focus position, we envision that HARC systems will bring the technology closer to implementation in laboratories for analysis of complex fluids with biological particles like cells and organelles.

    Place, publisher, year, edition, pages
    Institute of Physics Publishing (IOPP), 2021
    Keywords
    Microfluidics, Particle manipulation, Inertial Focusing
    National Category
    Fluid Mechanics and Acoustics
    Identifiers
    urn:nbn:se:uu:diva-427307 (URN)10.1088/1361-6439/abcae7 (DOI)000595695600001 ()
    Available from: 2020-12-06 Created: 2020-12-06 Last updated: 2024-01-15Bibliographically approved
    4. Fundamentals of Inertial Focusing in High Aspect Ratio Curved Microfluidics
    Open this publication in new window or tab >>Fundamentals of Inertial Focusing in High Aspect Ratio Curved Microfluidics
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Microfluidics exploiting the phenomenon of inertial focusing have attracted much attention in the last decade, as they provide the means to facilitate the detection and analysis of rare particles of interest in complex fluids such as blood and natural water. Although many interesting applications have been demonstrated, the systems remain difficult to engineer. A recently presented line of the technology, inertial focusing in High Aspect Ration Curved (HARC) microfluidics, has the potential to change this and make the benefits of inertial focusing more accessible to the community. In this paper, with experimental evidence and fluid simulations, we provide the two necessary equations to design the systems and successfully focus the desired targets in a single, stable, and high-quality position. Last, the experiments revealed an interesting scaling law of the lift force, which we believe provides a valuable insight into the phenomenon of inertial microfluidics.

    Keywords
    Microfluidics, Particle manipulation, Inertial Focusing
    National Category
    Fluid Mechanics and Acoustics
    Identifiers
    urn:nbn:se:uu:diva-427308 (URN)
    Available from: 2020-12-06 Created: 2020-12-06 Last updated: 2021-01-28Bibliographically approved
    5. High-resolution Particle Separation by Inertial Focusing in High Aspect Ratio Curved Microfluidics
    Open this publication in new window or tab >>High-resolution Particle Separation by Inertial Focusing in High Aspect Ratio Curved Microfluidics
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    The ability to focus, separate and concentrate specific targets in a fluid is essential for the analysis of complex samples such as biological fluids, where a myriad of different particles may be present. Inertial focusing is a very promising technology for such tasks. Recently, inertial focusing in High Aspect Ratio Curved (HARC) microchannels was presented, which simplifies the focusing and concentration of targets by positioning particles close together over a wide range of particle size and flow rate. However, by focusing all particles together, HARC systems lose an essential feature of inertial focusing: the possibility of particle separation by size. Within this work, we report that HARC systems not only do have the capacity to separate particles but can do so with extremely high resolution, which we demonstrate for particles with a size difference down to 80 nm.

    A model considering the main flow, the secondary flow and a simplified expression for the lift force in HARC microchannels was developed and proven accurate for the prediction of the performance of the systems. The concept was also demonstrated experimentally with three different sub-micron particles (0.79, 0.92 and 1.0 µm in diameter) in silicon-glass microchannels, whose separation distance could be modulated by the radius of the channel.

    With the capacity to focus sub-micron particles and to separate them with high resolution, inertial focusing in HARC systems are a technology with a strong potential for particle manipulation. We believe that this will facilitate the analysis of complex fluid samples containing bioparticles like bacteria, viruses or eukaryotic organelles.

    Keywords
    Microfluidics, Particle manipulation, Inertial Focusing
    National Category
    Fluid Mechanics and Acoustics
    Identifiers
    urn:nbn:se:uu:diva-427309 (URN)
    Available from: 2020-12-06 Created: 2020-12-06 Last updated: 2021-01-28Bibliographically approved
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  • 27.
    Cruz, Javier
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Hjort, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Stable 3D Inertial Focusing by High Aspect Ratio Curved Microfluidics2021In: Journal of Micromechanics and Microengineering, ISSN 0960-1317, E-ISSN 1361-6439, Vol. 31, article id 015008Article in journal (Refereed)
    Abstract [en]

    Fine manipulation of particles is essential for the analysis of complex samples such as blood or environmental water, where rare particles of interest may be masked by millions of others. Inertial focusing is amongst the most promising techniques for this task, enabling label-free manipulation of particles with sub-micron resolution at very high flow rates. However, the phenomenon still remains difficult to predict due to the focus position shifting in tortuous ways as function of the channel geometry, flow rate and particle size. Here, we present a new line of microfluidics that exploit inertial focusing in High Aspect Ratio Curved (HARC) microchannels and overcome this limitation. Consisting of a single curved channel, HARC systems provide a highly predictable, single focus position near the centre of the inner wall, largely independent of the flow rate and particle size.

    An explanation of the mechanism of migration and focus of particles, together with its governing equations, is provided based on simulations in COMSOL Multiphysics and experimental results. HARC microchannels built in silicon-glass were used for experimental validation, achieving a high quality, single focus position for a range of microparticles with sizes of 0.7 - 1 µm and bacterial cells (Escherichia coli). The recovery of 1 µm particles was 99.84% with a factor four in concentration.

    With a stable focus position, we envision that HARC systems will bring the technology closer to implementation in laboratories for analysis of complex fluids with biological particles like cells and organelles.

    Download full text (pdf)
    fulltext
  • 28.
    Cruz, Javier
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Fundamentals of Inertial Focusing in High Aspect Ratio Curved MicrofluidicsManuscript (preprint) (Other academic)
    Abstract [en]

    Microfluidics exploiting the phenomenon of inertial focusing have attracted much attention in the last decade, as they provide the means to facilitate the detection and analysis of rare particles of interest in complex fluids such as blood and natural water. Although many interesting applications have been demonstrated, the systems remain difficult to engineer. A recently presented line of the technology, inertial focusing in High Aspect Ration Curved (HARC) microfluidics, has the potential to change this and make the benefits of inertial focusing more accessible to the community. In this paper, with experimental evidence and fluid simulations, we provide the two necessary equations to design the systems and successfully focus the desired targets in a single, stable, and high-quality position. Last, the experiments revealed an interesting scaling law of the lift force, which we believe provides a valuable insight into the phenomenon of inertial microfluidics.

  • 29.
    Cruz, Javier
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    HARC Line within Inertial Focusing Systems - Separation of Sub-Micron Particles with Nanometer Resolution2021Conference paper (Refereed)
  • 30.
    Cruz, Javier
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    High-resolution Particle Separation by Inertial Focusing in High Aspect Ratio Curved MicrofluidicsManuscript (preprint) (Other academic)
    Abstract [en]

    The ability to focus, separate and concentrate specific targets in a fluid is essential for the analysis of complex samples such as biological fluids, where a myriad of different particles may be present. Inertial focusing is a very promising technology for such tasks. Recently, inertial focusing in High Aspect Ratio Curved (HARC) microchannels was presented, which simplifies the focusing and concentration of targets by positioning particles close together over a wide range of particle size and flow rate. However, by focusing all particles together, HARC systems lose an essential feature of inertial focusing: the possibility of particle separation by size. Within this work, we report that HARC systems not only do have the capacity to separate particles but can do so with extremely high resolution, which we demonstrate for particles with a size difference down to 80 nm.

    A model considering the main flow, the secondary flow and a simplified expression for the lift force in HARC microchannels was developed and proven accurate for the prediction of the performance of the systems. The concept was also demonstrated experimentally with three different sub-micron particles (0.79, 0.92 and 1.0 µm in diameter) in silicon-glass microchannels, whose separation distance could be modulated by the radius of the channel.

    With the capacity to focus sub-micron particles and to separate them with high resolution, inertial focusing in HARC systems are a technology with a strong potential for particle manipulation. We believe that this will facilitate the analysis of complex fluid samples containing bioparticles like bacteria, viruses or eukaryotic organelles.

  • 31.
    Cruz, Javier
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    High-resolution particle separation by inertial focusing in high aspect ratio curved microfluidics2021In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, article id 13959Article in journal (Refereed)
    Abstract [en]

    The ability to focus, separate and concentrate specific targets in a fluid is essential for the analysis of complex samples such as biological fluids, where a myriad of different particles may be present. Inertial focusing is a very promising technology for such tasks, and specially a recently presented variant, inertial focusing in High Aspect Ratio Curved systems (HARC systems), where the systems are easily engineered and focus the targets together in a stable position over a wide range of particle sizes and flow rates. However, although convenient for laser interrogation and concentration, by focusing all particles together, HARC systems lose an essential feature of inertial focusing: the possibility of particle separation by size. Within this work, we report that HARC systems not only do have the capacity to separate particles but can do so with extremely high resolution, which we demonstrate for particles with a size difference down to 80 nm. In addition to the concept for particle separation, a model considering the main flow, the secondary flow and a simplified expression for the lift force in HARC microchannels was developed and proven accurate for the prediction of the performance of the systems. The concept was also demonstrated experimentally with three different sub-micron particles (0.79, 0.92 and 1.0 mu m in diameter) in silicon-glass microchannels, where the resolution in the separation could be modulated by the radius of the channel. With the capacity to focus sub-micron particles and to separate them with high resolution, we believe that inertial focusing in HARC systems is a technology with the potential to facilitate the analysis of complex fluid samples containing bioparticles like bacteria, viruses or eukaryotic organelles.

    Download full text (pdf)
    FULLTEXT01
  • 32.
    Cruz, Javier
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Principia Lift Force – Empirical measurements of FL stray from modern theories2021Conference paper (Other academic)
    Download full text (pdf)
    fulltext
  • 33.
    Cruz, Javier
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    The upper limit and lift force within inertial focusing in high aspect ratio curved microfluidics2021In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, no 1, article id 6473Article in journal (Refereed)
    Abstract [en]

    Microfluidics exploiting the phenomenon of inertial focusing have attracted much attention in the last decade as they provide the means to facilitate the detection and analysis of rare particles of interest in complex fluids such as blood and natural water. Although many interesting applications have been demonstrated, the systems remain difficult to engineer. A recently presented line of the technology, inertial focusing in High Aspect Ratio Curved microfluidics, has the potential to change this and make the benefits of inertial focusing more accessible to the community. In this paper, with experimental evidence and fluid simulations, we provide the two necessary equations to design the systems and successfully focus the targets in a single, stable, and high-quality position. The experiments also revealed an interesting scaling law of the lift force, which we believe provides a valuable insight into the phenomenon of inertial focusing.

    Download full text (pdf)
    FULLTEXT01
  • 34.
    Cui, Jingwen
    et al.
    Lund Univ, Dept Chem, Ctr Anal & Synth CAS, POB 124, SE-22100 Lund, Sweden..
    Norberg, Mynta
    Lund Univ, Dept Chem, Ctr Anal & Synth CAS, POB 124, SE-22100 Lund, Sweden..
    Andersson, Martin
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala Univ, Ctr Nat Hazards & Disaster Sci CNDS, Dept Engineer Sci, Div Microsyst Technol, Box 534, SE-75121 Uppsala, Sweden..
    Klintberg, Lena
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala Univ, Ctr Nat Hazards & Disaster Sci CNDS, Dept Engineer Sci, Div Microsyst Technol, Box 534, SE-75121 Uppsala, Sweden..
    Sandahl, Margareta
    Lund Univ, Dept Chem, Ctr Anal & Synth CAS, POB 124, SE-22100 Lund, Sweden..
    Cunico, Larissa P.
    Lund Univ, Dept Chem, Ctr Anal & Synth CAS, POB 124, SE-22100 Lund, Sweden..
    Turner, Charlotta
    Lund Univ, Dept Chem, Ctr Anal & Synth CAS, POB 124, SE-22100 Lund, Sweden..
    Measurement of relative static permittivity and solvatochromic parameters of binary and ternary CO2-expanded green solvents2021In: Journal of Supercritical Fluids, ISSN 0896-8446, E-ISSN 1872-8162, Vol. 171, article id 105196Article in journal (Refereed)
    Abstract [en]

    CO2-expanded liquids (CXLs) is a class of solvent systems giving relatively low viscosity in comparison to neat organic solvents. The challenge is to achieve a high overall polarity of the CXL, despite the presence of compressed liquid CO2. In this study, the relative static permittivity (epsilon(r)) was measured for binary and ternary one-phase mixtures of CO2 + green solvent using an in-line microfluidic device. In addition, Kamlet-Taft solvatochromic parameters were experimentally determined, allowing the characterization of the polarizability, acidity, and basicity. Novel data is shown for binary and ternary systems of CO2 expanded ethanol and ethyl lactate, with or without glycerol or water added, at moderate conditions of pressure and temperature (8 MPa and 35 degrees C). One-phase CXLs systems of a wide relative permittivity range (7.7-75.3) at lowered viscosity were enabled, by mixing different green solvents with CO2.

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  • 35.
    Duoc, Vo Thanh
    et al.
    Hanoi Univ Sci & Technol HUST, Int Training Inst Mat Sci ITIMS, 1 Dai Co Viet, Hanoi 100000, Vietnam..
    Hung, Chu Manh
    Hanoi Univ Sci & Technol HUST, Int Training Inst Mat Sci ITIMS, 1 Dai Co Viet, Hanoi 100000, Vietnam..
    Nguyen, Hugo
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Van Duy, Nguyen
    Hanoi Univ Sci & Technol HUST, Int Training Inst Mat Sci ITIMS, 1 Dai Co Viet, Hanoi 100000, Vietnam..
    Van Hieu, Nguyen
    Phenikaa Univ, Phenikaa Inst Adv Study PIAS, Fac Elect & Elect Engn, Hanoi, Vietnam..
    Hoa, Nguyen Duc
    Hanoi Univ Sci & Technol HUST, Int Training Inst Mat Sci ITIMS, 1 Dai Co Viet, Hanoi 100000, Vietnam..
    Room temperature highly toxic NO2 gas sensors based on rootstock/scion nanowires of SnO2/ZnO, ZnO/SnO2, SnO2/SnO2 and, ZnO/ZnO2021In: Sensors and actuators. B, Chemical, ISSN 0925-4005, E-ISSN 1873-3077, Vol. 348, article id 130652Article in journal (Refereed)
    Abstract [en]

    Grafted structures between SnO2 and ZnO nanowires were realized in a two-step process of growth. First, the rootstocks of SnO2 or ZnO nanowires were synthesized by thermal evaporation technique. Second, a thin Au layer was sputter deposited on the sample and synthesis of nanowire scions of ZnO or SnO2, respectively, on the rootstocks was realized by thermal evaporation technique again. In both growth steps, SnO2 powder or a mixture of ZnO and carbon powders was use as source materials for the synthesis. Different rootstock/scion combinations of SnO2/ZnO, ZnO/SnO2 nanowires (called heterostructures) and ZnO/ZnO, SnO2/SnO2 nanowires (called homostructures) were synthesised. The fabricated grafted nanowires were examined by field-emission scanning electron microscope and their compositions were analyzed by energy dispersive spectroscopy and X-ray diffraction analysis. The test results indicate that this type of nanostructure material is very promising for NO2 gas sensing at ppt level at room temperature. Among the fabricated structures the SnO2/ZnO nanowires showed the best sensing performance with the high sensitivity and fast response and recovery time. We also discussed the gas sensing mechanism of the fabricated sensors based on the band diagram.

  • 36.
    Duoc, Vo Thanh
    et al.
    Hanoi Univ Sci & Technol HUST, Int Training Inst Mat Sci ITIMS, 1 Dai Co Viet, Hanoi, Vietnam..
    Nguyen, Hugo
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Ngoc, Trinh Minh
    Hanoi Med Univ, Dept Phys, 1 Ton That Tung, Hanoi, Vietnam..
    Xuan, Chu Thi
    Hanoi Univ Sci & Technol HUST, Int Training Inst Mat Sci ITIMS, 1 Dai Co Viet, Hanoi, Vietnam..
    Hung, Chu Manh
    Hanoi Univ Sci & Technol HUST, Int Training Inst Mat Sci ITIMS, 1 Dai Co Viet, Hanoi, Vietnam..
    Van Duy, Nguyen
    Hanoi Univ Sci & Technol HUST, Int Training Inst Mat Sci ITIMS, 1 Dai Co Viet, Hanoi, Vietnam..
    Hoa, Nguyen Duc
    Hanoi Univ Sci & Technol HUST, Int Training Inst Mat Sci ITIMS, 1 Dai Co Viet, Hanoi, Vietnam..
    Hydrogen gas sensor based on self-heating effect of SnO2/Pt thin film with ultralow power consumption2024In: International journal of hydrogen energy, ISSN 0360-3199, E-ISSN 1879-3487, Vol. 61, p. 774-782Article in journal (Refereed)
    Abstract [en]

    Self-heating of sensing elements on gas sensors is an effective solution to avoid using external heaters. In this paper, a self-heated hydrogen gas sensor is presented. The sensor was created using the DC sputtering method, which involved fabricating it on a thermal-insulating Kapton flexible substrate. This process utilized a thin film of SnO2 with thick 50 nm that was modified with nanoclusters of Pt, serving as the sensing material. The SnO2/Pt material film was analyzed for microstructure and composition by SEM, XRD, and XPS analysis. Infrared images show that the self-heating effect is mainly concentrated in the strip of gas-sensitive material. It showed many good performances, such as high sensitivity (able to detect down to 50 ppm of H2), good selectivity (poor response to CO, NH3, H2S, and NO2), the sensor's performance is little changed by environmental humidity, and low power consumption (89 μW at 5V). The sensor is also stable and low-cost, suitable for portable H2 detection devices due to its low generated heat and small size.

  • 37.
    Duy, Nguyen Van
    et al.
    Hanoi Univ Sci & Technol HUST, Int Training Inst Mat Sci ITIMS, 1 Dai Co Viet, Hanoi, Vietnam.
    Thai, Nguyen Xuan
    Hanoi Univ Sci & Technol HUST, Int Training Inst Mat Sci ITIMS, 1 Dai Co Viet, Hanoi, Vietnam.
    Ngoc, Trinh Minh
    Hanoi Univ Sci & Technol HUST, Int Training Inst Mat Sci ITIMS, 1 Dai Co Viet, Hanoi, Vietnam.
    Le, Dang Thi Thanh
    Hanoi Univ Sci & Technol HUST, Int Training Inst Mat Sci ITIMS, 1 Dai Co Viet, Hanoi, Vietnam.
    Hung, Chu Manh
    Hanoi Univ Sci & Technol HUST, Int Training Inst Mat Sci ITIMS, 1 Dai Co Viet, Hanoi, Vietnam.
    Nguyen, Hugo
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Tonezzer, Matteo
    IMEM CNR, Sede Trento FBK, Via Cascata 56-C, I-38123 Povo, Trento, Italy.
    Hieu, Nguyen Van
    Phenikaa Univ, Fac Elect & Elect Engn, Hanoi, Vietnam.
    Hoa, Nguyen Duc
    Hanoi Univ Sci & Technol HUST, Int Training Inst Mat Sci ITIMS, 1 Dai Co Viet, Hanoi, Vietnam.
    Design and fabrication of effective gradient temperature sensor array based on bilayer SnO2/Pt for gas classification2022In: Sensors and actuators. B, Chemical, ISSN 0925-4005, E-ISSN 1873-3077, Vol. 351, article id 130979Article in journal (Refereed)
    Abstract [en]

    Classification of different gases is important, and it is possible to use different gas sensors for this purpose. Electronic noses, for example, combine separated gas sensors into an array for detecting different gases. However, the use of separated sensors in an array suffers from being bulky, high-energy consumption and complex fabrication processes. Generally, gas sensing properties, including gas selectivity, of semiconductor gas sensors are strongly dependent on their working temperature. It is therefore feasible to use a single device composed of identical sensors arranged in a temperature gradient for classification of multiple gases. Herein, we introduce a design for simple fabrication of gas sensor array based on bilayer Pt/SnO2 for real-time monitoring and classification of multiple gases. The study includes design simulation of the sensor array to find an effective gradient temperature, fabrication of the sensors and test of their performance. The array, composed of five sensors, was fabricated on a glass substrate without the need of backside etching to reduce heat loss. A SnO2 thin film sensitized with Pt on top deposited by sputtering was used as sensing material. The sensor array was tested against different gases including ethanol, methanol, isopropanol, acetone, ammonia, and hydrogen. Radar plots and principal component analysis were used to visualize the distinction of the tested gases and to enable effective classification.

  • 38.
    Duy, Nguyen Van
    et al.
    Hanoi Univ Sci & Technol HUST, ITIMS, Hanoi, Vietnam.
    Trang, Duong Thi Thuy
    Hanoi Univ Sci & Technol HUST, ITIMS, Hanoi, Vietnam.
    Le, Dang Thi Thanh
    Hanoi Univ Sci & Technol HUST, ITIMS, Hanoi, Vietnam.
    Hung, Chu Manh
    Hanoi Univ Sci & Technol HUST, ITIMS, Hanoi, Vietnam.
    Tonezzer, Matteo
    Univ Trento, Fdn Edmund Mach, Ctr Agr Food Environm, Via E Mach 1, I-38010 San Michele All Adige, Italy.;IMEM CNR, Via Cascata 56 C, I-38123 Trento, Italy.
    Nguyen, Hugo
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Hoa, Nguyen Duc
    Hanoi Univ Sci & Technol HUST, ITIMS, Hanoi, Vietnam.
    Enhancement of NH3 gas sensing with Ag-Pt co-catalyst on SnO2 nanofilm towards medical diagnosis2023In: Thin Solid Films, ISSN 0040-6090, E-ISSN 1879-2731, Vol. 767, article id 139682Article in journal (Refereed)
    Abstract [en]

    Exhaled breath analysis is a noninvasive diagnostic method for fatal disease monitoring and screening, which is recently gained extensive interest of researchers worldwide emphasizing on the development of effective chemiresistive gas sensor for practical application. Here, the Ag-Pt bimetallic nanoparticles were used to deco-rate nanofilms of SnO2 making different gas sensors with high performance. We found that the bimetal alloy improved the sensor performance significantly with super sensitivity as compared with the separate Ag and Pt catalyst. The right ratio of the bimetal made the sensor very sensitive to NH3, so that it was able to quickly (12 s) detect 1 parts-per-million of NH3 with a response of 4.31 at a temperature of 250 degrees C. The sensor limit of detection for NH3 was less than 10 parts-per-billion. The response of the sensor was negligibly affected by humidity and interfering gases. The results showed that the tiny, robust, and inexpensive sensor developed in this work can be used in breath analysis for early diagnosis via NH3 monitoring.

  • 39.
    Ewald, Johannes
    et al.
    ‎Johannes Gutenberg Univ Mainz, Inst Organ Chem, Duesbergweg 10-14, D-55128 Mainz, Germany.
    Blankenburg, Jan
    ‎Johannes Gutenberg Univ Mainz, Inst Organ Chem, Duesbergweg 10-14, D-55128 Mainz, Germany; Grad Sch Mat Sci Mainz, Staudinger Weg 9, D-55128 Mainz, Germany.
    Worm, Matthias
    ‎Johannes Gutenberg Univ Mainz, Inst Organ Chem, Duesbergweg 10-14, D-55128 Mainz, Germany.
    Besch, Laura
    Johannes Gutenberg Univ Mainz, Inst Inorgan Chem & Analyt Chem, Duesbergweg 10-14, D-55128 Mainz, Germany.
    Unger, Ronald E.
    Johannes Gutenberg Univ Mainz, Inst Pathol, Obere Zahlbacher Str 63, D-55101 Mainz, Germany.
    Tremel, Wolfgang
    Johannes Gutenberg Univ Mainz, Inst Inorgan Chem & Analyt Chem, Duesbergweg 10-14, D-55128 Mainz, Germany.
    Frey, Holger
    ‎Johannes Gutenberg Univ Mainz, Inst Organ Chem, Duesbergweg 10-14, D-55128 Mainz, Germany.
    Pohlit, Hannah
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. ‎Johannes Gutenberg Univ Mainz, Inst Organ Chem, Duesbergweg 10-14, D-55128 Mainz, Germany.
    Acid-Cleavable Poly(ethylene glycol) Hydrogels Displaying Protein Release at pH 52020In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 26, no 13, p. 2947-2953Article in journal (Refereed)
    Abstract [en]

    PEG is the gold standard polymer for pharmaceutical applications, however it lacks degradability. Degradation under physiologically relevant pH as present in endolysosomes, cancerous and inflammatory tissues is crucial for many areas. The authors present anionic ring‐opening copolymerization of ethylene oxide with 3,4‐epoxy‐1‐butene (EPB) and subsequent modification to introduce acid‐degradable vinyl ether groups as well as methacrylate (MA) units, enabling radical cross‐linking. Copolymers with different molar ratios of EPB, molecular weights (Mn) up to 10 000 g mol−1 and narrow dispersities (Đ<1.05) were prepared. Both the P(EG‐coisoEPB)MA copolymer and the hydrogels showed pH‐dependent, rapid hydrolysis at pH 5–6 and long‐term storage stability at neutral pH (pH 7.4). By designing the degree of polymerization and content of degradable vinyl ether groups, the release time of an entrapped protein OVA‐Alexa488 can be tailored from a few hours to several days (hydrolysis half‐life time t1/2 at pH 5: 13 h to 51 h).

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  • 40.
    Fornell, Anna
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Lund Univ, MAX Lab 4, S-22484 Lund, Sweden.
    Baasch, Thierry
    Lund Univ, Dept Biomed Engn, S-22100 Lund, Sweden.
    Johannesson, Carl
    Lund Univ, Dept Biomed Engn, S-22100 Lund, Sweden.
    Nilsson, Johan
    Lund Univ, Dept Biomed Engn, S-22100 Lund, Sweden.
    Tenje, Maria
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Binary acoustic trapping in a glass capillary2021In: Journal of Physics D: Applied Physics, ISSN 0022-3727, E-ISSN 1361-6463, Vol. 54, no 35, article id 355401Article in journal (Refereed)
    Abstract [en]

    Acoustic trapping is a useful method for handling biological samples in microfluidic systems. The aim of this work is twofold: first to investigate the physics behind acoustic trapping in a glass capillary and secondly to perform binary acoustic trapping. The latter is achieved by increasing the density of the fluid in the trapping channel. The trapping device consisted of a glass capillary with a rectangular inner cross-section (height 200 µm × width 2000 µm) equipped with a small piezoelectric transducer. The piezoelectric transducer was actuated at 4 MHz to generate a localised half-wavelength acoustic standing-wave-field in the capillary, comprising of a pressure field and a velocity field. Under acoustic actuation, only particles with higher density than the fluid, i.e. having a positive dipole scattering coefficient, were trapped in the flow direction. The numerical and analytical modelling of the system show that the trapping force which retains the particles against the flow depends only on the dipole scattering coefficient in the pressure nodal plane of the acoustic field. The analytical model also reveals that the retention force is proportional to the dipole scattering coefficient, which agrees with our experimental findings. Next, we showed that in a mixture of melamine particles and polystyrene particles in a high-density fluid it is possible to selectively trap melamine particles, since melamine particles have higher density than polystyrene particles.

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  • 41.
    Fornell, Anna
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Johannesson, Carl
    Lund Univ, Dept Biomed Engn, Lund, Sweden..
    Searle, Sean
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Natl Univ Singapore, Dept Biomed Engn, Singapore, Singapore..
    Happstadius, Axel
    Lund Univ, Dept Biomed Engn, Lund, Sweden..
    Nilsson, Johan
    Lund Univ, Dept Biomed Engn, Lund, Sweden..
    Tenje, Maria
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Trapping of Cell-Laden Hyaluronic Acid-Acrylamide Hydrogel Droplets using Bulk Acoustic Waves2019In: 2019 20th International Conference on Solid-State Sensors, Actuators and Microsystems & Eurosensors XXXIII (TRANSDUCERS & EUROSENSORS XXXIII), IEEE , 2019, p. 2352-2355Conference paper (Refereed)
    Abstract [en]

    In this paper an acoustofluidic system to trap hydrogel droplets is shown. The presented trapping method is label-free, biocompatible and operated in non-contact mode. The results show that the droplets can be trapped at flow rates up to 76 mu L/min which corresponds to an average flow speed of 3.2 mm/s. Moreover, it is shown that the droplets can be trapped for several hours, thus allowing for studies of the encapsulated cells over time. An application of the system is shown by performing on-chip cell nuclei staining.

  • 42.
    Fornell, Anna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Liu, Zhenhua
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Optimisation of the droplet split design for high acoustic particle enrichment in droplet microfluidics2020In: Microelectronic Engineering, ISSN 0167-9317, E-ISSN 1873-5568, Vol. 226, article id 111303Article in journal (Refereed)
    Abstract [en]

    We have characterised three droplet split designs for acoustic particle enrichment in water-in-oil droplets. The microfluidic channel design included a droplet generation junction, acoustic focusing channel and a trident-shaped droplet split. The microfluidic channels were dry-etched in silicon and sealed with glass lids by anodic bonding. To each microfluidic chip a piezoelectric transducer was glued, and at actuation of the transducer at the fundamental resonance frequency of the acoustic focusing channel (1.91–1.93 MHz), a half wavelength standing wave field was created between the channel walls. The acoustic force focused the encapsulated particles (3.2 μm, 4.8 μm and 9.9 μm diameter polystyrene microbeads) to the centre-line of the droplets, and when the droplets reached the droplet split the particles were directed into the centre daughter droplets. The results show that the design of the droplet split and the flow ratio between the centre and side outlet channels are the main factors that affect the particle enrichment and particle recovery in the centre daughter droplets. The highest particle enrichment was achieved in the droplet split design having the smallest centre channel (38 μm wide). Using this microfluidic chip design, we demonstrate up to 16.7-fold enrichment of 9.9 μm diameter polystyrene microbeads in the centre daughter droplets. This is almost three times higher particle enrichment than what has previously been presented using other intra-droplet particle enrichment techniques. Moreover, the acoustic technique is label-free and biocompatible.

  • 43.
    Fornell, Anna
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. MAXIV Laboratory, Lund University, 22484, Lund, Sweden.
    Pohlit, Hannah
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Shi, Qian
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tenje, Maria
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Acoustic focusing of beads and cells in hydrogel droplets2021In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, no 1, article id 7479Article in journal (Refereed)
    Abstract [en]

    The generation of hydrogel droplets using droplet microfluidics has emerged as a powerful tool with many applications in biology and medicine. Here, a microfluidic system to control the position of particles (beads or astrocyte cells) in hydrogel droplets using bulk acoustic standing waves is presented. The chip consisted of a droplet generator and a 380 µm wide acoustic focusing channel. Droplets comprising hydrogel precursor solution (polyethylene glycol tetraacrylate or a combination of polyethylene glycol tetraacrylate and gelatine methacrylate), photoinitiator and particles were generated. The droplets passed along the acoustic focusing channel where a half wavelength acoustic standing wave field was generated, and the particles were focused to the centre line of the droplets (i.e. the pressure nodal line) by the acoustic force. The droplets were cross-linked by exposure to UV-light, freezing the particles in their positions. With the acoustics applied, 89 ± 19% of the particles (polystyrene beads, 10 µm diameter) were positioned in an area ± 10% from the centre line. As proof-of-principle for biological particles, astrocytes were focused in hydrogel droplets using the same principle. The viability of the astrocytes after 7 days in culture was 72 ± 22% when exposed to the acoustic focusing compared with 70 ± 19% for samples not exposed to the acoustic focusing. This technology provides a platform to control the spatial position of bioparticles in hydrogel droplets, and opens up for the generation of more complex biological hydrogel structures.

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  • 44.
    Fornell, Anna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Söderbäck, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Liu, Zhenhua
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Moreira, Milena
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Fabrication of Silicon Microfluidic Chips for Acoustic Particle Focusing Using Direct Laser Writing2020In: Micromachines, E-ISSN 2072-666X, Vol. 11, no 2, article id 113Article in journal (Refereed)
    Abstract [en]

    We have developed a fast and simple method for fabricating microfluidic channels in silicon using direct laser writing. The laser microfabrication process was optimised to generate microfluidic channels with vertical walls suitable for acoustic particle focusing by bulk acoustic waves. The width of the acoustic resonance channel was designed to be 380 µm, branching into a trifurcation with 127 µm wide side outlet channels. The optimised settings used to make the microfluidic channels were 50% laser radiation power, 10 kHz pulse frequency and 35 passes. With these settings, six chips could be ablated in 5 h. The microfluidic channels were sealed with a glass wafer using adhesive bonding, diced into individual chips, and a piezoelectric transducer was glued to each chip. With acoustic actuation at 2.03 MHz a half wavelength resonance mode was generated in the microfluidic channel, and polystyrene microparticles (10 µm diameter) were focused along the centre-line of the channel. The presented fabrication process is especially interesting for research purposes as it opens up for rapid prototyping of silicon-glass microfluidic chips for acoustofluidic applications.

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  • 45.
    Fu, Le
    et al.
    Cent South Univ, Sch Mat Sci & Engn, Changsha, Peoples R China..
    Zhou, Huasi
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Klintberg, Lena
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Fabrication of mechanically robust nanoporous ZrSiO4 ceramics at low temperature with a low doping level of Mn dopant2024In: International Journal of Applied Ceramic Technology, ISSN 1546-542X, E-ISSN 1744-7402, Vol. 21, no 3, p. 1954-1964Article in journal (Refereed)
    Abstract [en]

    Zircon (ZrSiO4) ceramics have been widely used in many fields due to their excellent physical and chemical properties. However, ZrSiO4 ceramics typically possess moderately low mechanical properties, which hinders their wider application. Meanwhile, elevated temperatures (similar to 1500 degrees C) are required to obtain high-purity synthetic ZrSiO4 ceramics, which is time- and energy-consuming. In the present study, we prepared mechanically robust ZrSiO4 ceramics at low temperature (similar to 1170 degrees C) with a low doping level of Mn dopant (<2 mol%). The ZrSiO4 ceramic processed by hot isostatic pressing with .5 mol% Mn dopant achieved the highest flexural strength (512 MPa), elastic modulus (341 GPa), and nanohardness (20.8 GPa). These values are significantly higher than conventional ZrSiO4 ceramics. The strengthening mechanisms of the prepared ZrSiO4 ceramics were attributed to the formation of homogeneously-distributed nanopores due to incomplete densification and submicron ZrSiO4 grains (similar to 300 nm). The nanopores avoided stress concentration and deflected microcracks during loading, and the submicron ZrSiO4 grains endowed the ZrSiO4 ceramics with grain refinement strengthening. The results reported in this study would offer guidance to fabricate mechanically robust ZrSiO4 ceramics at low temperatures with a low doping level of dopant.

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  • 46.
    Göransson, Sofia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Carbon dioxide-based pump system for portable HPLC equipment2022Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    To make chemical analysis available both practically and economically, one approach is to miniaturise the equipment needed for the analysis. High-performance liquid chromatography (HPLC) is an example of a flow chemistry analysis system where active work is performed to achieve miniaturised systems. In this thesis, the focus is on creating a miniatyrised pump system constructed of pressurised CO2 (PCO) and a microfluidic chip with a restriction channel. The assignment of the PCO is to force a separate medium, which in this case is water, through the remaining system. The pump system will therefore be defined as pressure-driven, which has advantages as pulse-free flows. Utilising the latent energy from the PCO also reduces the need for electrical power, hence allowing a smaller battery. However, the pressure from the carbon dioxide source will gradually decrease as the content is consumed. To obtain continuous pressure, heaters have been integrated into the chip, and thus, the pressure drop can be controlled by changing the viscosity and density of the through-flowing fluid. A cooling table was also used to enable the cooling of the chip and thus further increase the pressure drop. PID control was implemented for the temperature to be adjusted to maintain a constant pressure downstream of the chip. By using this technology, runs of just over 80 minutes have been achieved with a pressure of 60 bar and a flow of 100 µl/min downstream, with a maximal error of around 0.03 bar. Then a chip adapted for water was used to control the water flow. Chips adapted for carbon dioxide placed right after the carbon dioxide source were also tested andruns of just over 10 minutes at 75 bar and 100 µl/min could be achieved with a maximal error closer to 1 bar. The pressure vessel used held a maximum of 100 ml of CO2 at 60 bar. The idea is that the pump system, in the end, will be applied for portable HPLC, and the PCO will then be stored in a cartridge, but in the experiments, a turned-off ISCO pump functioned as a carbon dioxide source. 

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  • 47.
    Hjort, Klas
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Mårtensson, Gustaf
    Mycronic AB.
    Vicini, Isella
    Warrant Hub S.p.A..
    SINTEC Final Workshop “Smart Bioelectronic and Wearable Systems”2023In: Smart Bioelectronic and Wearable Systems: SINTEC Final Workshop / [ed] Klas Hjort, Gustaf Mårtensson, Isella Vicini, Uppsala: Uppsala universitet, 2023, p. 5-5Conference paper (Other academic)
  • 48.
    Hjort, Klas
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Vicini, IsellaWarrant Hub S.p.A..Mårtensson, GustafMycronic AB; School of Chemistry, Biotechnology and Health, The Royal Institute of Technology, Sweden..
    Smart Bioelectronic and Wearable Systems: SINTEC Final Workshop: Proceedings2023Conference proceedings (editor) (Other academic)
    Abstract [en]

    The aim of the SINTEC Final Workshop “Smart Bioelectronic and Wearable Systems” is to highlight European research focused on the ultra-flexible, stretchable, soft and conformal technologies, and networking with companies and European funded projects to discover future opportunities in the stretchable electronics market.

    Topics include: Bioelectronics, Stretchable and conformal electronics, Wearable sensors and actuators, Smart patches and clothings, Wearables for sports and healthcare application, Intra-body communication, and Network solutions for wearable health and sport monitoring.

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    Smart Bioelectronic and Wearable Systems - SINTEC Workshop
  • 49.
    Hong, Jun
    et al.
    Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Joint Int Res Lab Metab & Dev Sci, Shanghai 200240, Peoples R China..
    Shi, Qian
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Biswas, Sukumar
    Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Joint Int Res Lab Metab & Dev Sci, Shanghai 200240, Peoples R China..
    Jiang, Shang-Chuan
    Food & Agr Org United Nations, Plant Prod & Protect Div, Rural & Urban Crop & Mechanizat Syst, I-00153 Rome, Italy..
    Shi, Jianxin
    Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Joint Int Res Lab Metab & Dev Sci, Shanghai 200240, Peoples R China.;Food & Agr Org United Nations, Plant Prod & Protect Div, Rural & Urban Crop & Mechanizat Syst, I-00153 Rome, Italy..
    Moving genome edited crops forward from the laboratory bench to the kitchen table2021In: Food Control, ISSN 0956-7135, E-ISSN 1873-7129, Vol. 122, article id 107790Article, review/survey (Refereed)
    Abstract [en]

    Targeted nuclease based genome editing technology particularly clustered regularly interspaced short palindromic repeats (CRISPR) that allows to manipulate virtually almost any genomic sequences has greatly facilitated both basic and applied researches in plants. However, so far, very few of them has entered to the field and much less to the kitchen table. This review starts with a brief summary of current status of the application of genome editing in crop science and crop breeding and, then identifies technical, ethical, intellectual and other challenges for the commercialization of genome edited crops. This review explores further advances in the specificity and the prediction and detection of off-targets of CRISPR system, and highlights the importance of molecular characterization and the introduction of novel techniques such as nanotechnology to CRISPR system. Finally, this review calls for collaborative efforts in proposing principles and guidelines for moving genome edited crops forward from the laboratory bench to the kitchen table, and emphasizes the equal importance of public outreach.

  • 50.
    Hurtigh Grabe, Vilma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Visualization, modeling and consequences of residual stresses in glass frit sealing of a UV light source2023Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    PureFize Technologies AB develops and manufactures a broadband ultraviolet (UVC) light technology device that is mercury-free and based on nanotechnology, using the principle of field emission. The light source is made of Ti and glass, which are hermetically bonded, using a low-temperature glass frit, at elevated temperatures. The bonding procedure will induce stresses in the device originating from the mismatch of the coefficient of thermal expansion (CTE) between the materials. Brittle materials, as glass, withstands tensile stresses poorly. Therefore, the stress magnitude and distribution needs to be understood. 

    This work develops a quality inspection method for the glass bond and internal stresses, as well as stress simulations of the device, to be used in production at the company.

    The glass bond width and the internal stresses in the device were classified and analyzed by light optical microscopy and by polarised light optical microscopy. The optical analysis was followed by pressure tests of the devices using a chamber that allowed for pressurized air up to 7 bar. In parallell with the experimental work, stress and deformation simulations of the device using the finite element method (FEM) was made.

    Data collected from the inspections and pressure tests were compiled and analyzed, showing clear connections between the glass bond quality and the device's ability to withstand external pressure. A narrow glass bond could withstand external pressure poorly, whereas a wide glass bond could withstand external pressure well. Correlations could be made both between the glass bond appearance and the stress patterns, as well as between the FEM simulations and the stress patterns in the device. It is clear that the stresses induced in the device after bonding originates from the CTE mismatch of the bonded components when cooling it from the bonding temperature to room temperature. The pressure testing method proved to be an efficient way of verifying the maximum pressure capacity of the devices. 

    The knowledge from this thesis can be used when further investigating induced stresses from glas frit bonding.

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