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Fornell, A., Cushing, K., Nilsson, J. & Tenje, M. (2018). Binary particle separation in droplet microfluidics using acoustophoresis. Applied Physics Letters, 112(6), Article ID 063701.
Open this publication in new window or tab >>Binary particle separation in droplet microfluidics using acoustophoresis
2018 (English)In: Applied Physics Letters, ISSN 0003-6951, E-ISSN 1077-3118, Vol. 112, no 6, article id 063701Article in journal (Refereed) Published
Abstract [en]

We show a method for separation of two particle species with different acoustic contrasts originally encapsulated in the same droplet in a continuous two-phase system. This was realized by using bulk acoustic standing waves in a 380 mu m wide silicon-glass microfluidic channel. Polystyrene particles (positive acoustic contrast particles) and in-house synthesized polydimethylsiloxane (PDMS) particles (negative acoustic contrast particles) were encapsulated inside water-in-oil droplets either individually or in a mixture. At acoustic actuation of the system at the fundamental resonance frequency, the polystyrene particles were moved to the center of the droplet (pressure node), while the PDMS particles were moved to the sides of the droplet (pressure anti-nodes). The acoustic particle manipulation step was combined in series with a trifurcation droplet splitter, and as the original droplet passed through the splitter and was divided into three daughter droplets, the polystyrene particles were directed into the center daughter droplet, while the PDMS particles were directed into the two side daughter droplets. The presented method expands the droplet microfluidics tool-box and offers new possibilities to perform binary particle separation in droplet microfluidic systems.

National Category
Physical Sciences Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-347079 (URN)10.1063/1.5020356 (DOI)000424703200040 ()
Funder
Swedish Research CouncilThe Crafoord FoundationStiftelsen Olle Engkvist Byggmästare
Available from: 2018-03-26 Created: 2018-03-26 Last updated: 2018-04-04Bibliographically approved
Atif, A. R., Carter, S.-S., Pujari-Palmer, M., Tenje, M. & Mestres, G. (2018). Bone Cement Embedded in a Microfluidic Device. In: : . Paper presented at Micronano System Workshop (MSW), Aalto University, Espoo, Finland, May 13-15, 2018.
Open this publication in new window or tab >>Bone Cement Embedded in a Microfluidic Device
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2018 (English)Conference paper, Poster (with or without abstract) (Refereed)
Abstract [en]

Calcium phosphate cements (CPCs) have a great potential in the treatment of bone disorders due to their excellent biocompatibility. Although CPCs are promising when implanted in vivo, there is poor correlation between in vitro and in vivo studies. This could be because most conventional in vitro systems lack a 3D architecture, or dynamic conditions (i.e. a continuous refreshment stream). The aim of this work is to embed CPCs into a microfluidic system and evaluate ion and protein exchange at different flow rates.

Keywords
Calcium Phosphate Cements, Microfluidic Chip, Continuous flow, Biomaterial Evaluation, Bone implants, Cells
National Category
Other Materials Engineering
Identifiers
urn:nbn:se:uu:diva-363447 (URN)
Conference
Micronano System Workshop (MSW), Aalto University, Espoo, Finland, May 13-15, 2018
Funder
Swedish Research Council Formas, 2016-00781Knut and Alice Wallenberg Foundation, WAF 2016-0112Swedish Research Council, 2017-05051
Available from: 2018-10-18 Created: 2018-10-18 Last updated: 2018-10-19
Searle, S., Porras, A. M., Barbe, L., Shi, L., Ossipov, D. A., Trau, D. & Tenje, M. (2018). Hyaluronic acid based hydrogel droplets: A potential injectable cell culture scaffold. In: : . Paper presented at EUROoC, Stuttgart, Germany. 24 and 35 May, 2018..
Open this publication in new window or tab >>Hyaluronic acid based hydrogel droplets: A potential injectable cell culture scaffold
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2018 (English)Conference paper, Oral presentation only (Other academic)
Abstract [en]

Introduction

Cell culture scaffolds such as hydrogels give support and structure for cultured cells in 3D environments that better mimic in vivo conditions [1]. Hyaluronic acid (HA) derived hydrogels are particularly attractive scaffold materials, due to their high water content, and its high presence in the extracellular matrix of a multitude of tissues in the human body [2]. Adequate diffusion of oxygen and nutrients however, is generally limited to a depth of 200 µm in bulk hydrogels [3], heavily limiting their applicability to relatively large size constructs. We propose the use of droplet-based microfluidics to produce monodisperse HA-derived injectable microgel droplets which could enable the diffusion of nutrients and metabolites, while maintaining a size in which encapsulating sufficient cells to allow cell-cell interactions and proliferation would be possible.

 

Experimental results

Hyaluronic acid acrylamide (HA-am) was synthesized by partially modifying high molecular weight sodium hyaluronan with a N-(2-aminoethyl)acrylamide linker. Degree of modification was confirmed by NMR to be of 20%. HA-am bulk hydrogels were formed by exposing a solution of HA-am and photoinitiator Irgacure 2959 (0.4 % w/v) to a UV light source of 365 nm wavelength. Gel droplets were produced in a PDMS microfluidic device designed in a flow focusing geometry. In order to simulate cell encapsulation in the microgel, hydrogel precursor mixtures were prepared as for bulk hydrogels with the addition of polystyrene beads (10µm in diameter) at a concentration of 10 million beads ml-1. For the oil phase, a fluorinated oil (Novec 7500, 3M) with 0.5% surfactant (PicoSurf 1) was used. The flow rates for the oil phase and aqueous phase were adjusted to 15 and 5 µl min-1, respectively to produce highly monodisperse droplets of 151 µm in average diameter. Collected droplets were polymerized by exposing to UV light, washed and transferred to an aqueous solution.

 

 

Conclusion

Highly monodisperse microgels containing microbeads were obtained. We demonstrate that photocrosslinkable hydrogel droplets can be produced from HA-am in a microfluidic flow-focusing chip which could enable the encapsulation of cells and the use of the droplets as injectable cell culture scaffolds.

 

References

[1]       G. D. Nicodemus and S. J. Bryant, “Cell Encapsulation in Biodegradable Hydrogels for Tissue Engineering Applications,” Tissue Eng. Part B Rev., vol. 14, no. 2, pp. 149–165, Jun. 2008.

[2]       J. A. Burdick and G. D. Prestwich, “Hyaluronic acid hydrogels for biomedical applications,” Adv. Mater., vol. 23, no. 12, pp. 41–56, Mar. 2011.

[3]       H. Huang, Y. Yu, Y. Hu, X. He, O. Berk Usta, and M. L. Yarmush, “Generation and manipulation of hydrogel microcapsules by droplet-based microfluidics for mammalian cell culture,” Lab Chip, vol. 17, no. 11, pp. 1913–1932, 2017.

National Category
Engineering and Technology
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
urn:nbn:se:uu:diva-357613 (URN)
Conference
EUROoC, Stuttgart, Germany. 24 and 35 May, 2018.
Available from: 2018-08-17 Created: 2018-08-17 Last updated: 2018-08-22Bibliographically approved
Carter, S.-S., Atif, A. R., Lanekoff, I., Tenje, M. & Mestres, G. (2018). Improving the biocompatibility of PDMS by improving its curing time and temperature. In: : . Paper presented at EUROoC (organ on a chip).
Open this publication in new window or tab >>Improving the biocompatibility of PDMS by improving its curing time and temperature
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2018 (English)Conference paper, Poster (with or without abstract) (Other academic)
National Category
Medical Materials
Identifiers
urn:nbn:se:uu:diva-353156 (URN)
Conference
EUROoC (organ on a chip)
Available from: 2018-06-11 Created: 2018-06-11 Last updated: 2018-06-19
Johansson, S., Porras, A. M., Searle, S., Barbe, L. & Tenje, M. (2018). Integrated transparent electrodes in an organs-on-chip system. In: : . Paper presented at Micronano System Workshop (MSW), Espoo, Finland, May 13th to 18th 2018.
Open this publication in new window or tab >>Integrated transparent electrodes in an organs-on-chip system
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2018 (English)Conference paper, Oral presentation only (Refereed)
National Category
Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-363355 (URN)
Conference
Micronano System Workshop (MSW), Espoo, Finland, May 13th to 18th 2018
Available from: 2018-10-17 Created: 2018-10-17 Last updated: 2018-10-18Bibliographically approved
Fornell, A., Garofalo, F., Nilsson, J., Bruus, H. & Tenje, M. (2018). Intra-droplet acoustic particle focusing: simulations and experimental observations. Microfluidics and Nanofluidics, 22(75)
Open this publication in new window or tab >>Intra-droplet acoustic particle focusing: simulations and experimental observations
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2018 (English)In: Microfluidics and Nanofluidics, ISSN 1613-4982, E-ISSN 1613-4990, Vol. 22, no 75Article in journal (Refereed) Published
Abstract [en]

The aim of this paper is to study resonance conditions for acoustic particle focusing inside droplets in two-phase microfluidic systems. A bulk acoustic wave microfluidic chip was designed and fabricated for focusing microparticles inside aqueous droplets (plugs) surrounded by a continuous oil phase in a 380-μm-wide channel. The quality of the acoustic particle focusing was investigated by considering the influence of the acoustic properties of the continuous phase in relation to the dispersed phase. To simulate the system and study the acoustic radiation force on the particles inside droplets, a simplified 3D model was used. The resonance conditions and focusing quality were studied for two different cases: (1) the dispersed and continuous phases were acoustically mismatched (water droplets in fluorinated oil) and (2) the dispersed and continuous phases were acoustically matched (water droplets in olive oil). Experimentally, we observed poor acoustic particle focusing inside droplets surrounded by fluorinated oil while good focusing was observed in droplets surrounded by olive oil. The experimental results are supported qualitatively by our simulations. These show that the acoustic properties (density and compressibility) of the dispersed and continuous phases must be matched to generate a strong and homogeneous acoustic field inside the droplet that is suitable for high-quality intra-droplet acoustic particle focusing.

Place, publisher, year, edition, pages
Springer Berlin/Heidelberg, 2018
Keywords
Acoustophoresis, Droplets, Particle manipulation, Two-phase microfluidics, Ultrasound
National Category
Engineering and Technology
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
urn:nbn:se:uu:diva-356418 (URN)10.1007/s10404-018-2094-9 (DOI)000436895700001 ()
Funder
Swedish Research CouncilThe Crafoord FoundationKnut and Alice Wallenberg Foundation, KAW 2012.0023Stiftelsen Olle Engkvist ByggmästareStiftelsen Längmanska kulturfondenStiftelsen Olle Engkvist Byggmästare
Available from: 2018-07-26 Created: 2018-07-26 Last updated: 2018-09-06Bibliographically approved
Johansson, S., Porras, A. M., Searle, S., Barbe, L., Kubart, T. & Tenje, M. (2018). Organs-on-Chip System with Integrated Transparent Conductive Oxide Electrodes. In: : . Paper presented at EUROoC (Organ on a Chip), Stuttgart, Germany, 24-25 May, 2018.
Open this publication in new window or tab >>Organs-on-Chip System with Integrated Transparent Conductive Oxide Electrodes
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2018 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-363365 (URN)
Conference
EUROoC (Organ on a Chip), Stuttgart, Germany, 24-25 May, 2018
Available from: 2018-10-17 Created: 2018-10-17 Last updated: 2018-10-18Bibliographically approved
Tenje, M., Fornell, A., Ohlin, M. & Nilsson, J. (2018). Particle Manipulation Methods in Droplet Microfluidics. Analytical Chemistry, 90(3), 1434-1443
Open this publication in new window or tab >>Particle Manipulation Methods in Droplet Microfluidics
2018 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 90, no 3, p. 1434-1443Article in journal (Refereed) Published
Abstract [en]

This Feature article describes the different particle manipulation techniques available in the droplet microfluidics tool-box to handle particles encapsulated inside droplets and to manipulate whole droplets. We address the advantages and disadvantages of the different techniques to guide new users.  

National Category
Analytical Chemistry Engineering and Technology
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
urn:nbn:se:uu:diva-348921 (URN)10.1021/acs.analchem.7b01333 (DOI)000424730600002 ()29188994 (PubMedID)
Funder
Swedish Research Council, 621-2013-5920The Crafoord Foundation, 20130569
Available from: 2018-04-25 Created: 2018-04-25 Last updated: 2018-10-17Bibliographically approved
Searle, S., Porras, A. M., Barbe, L., Shi, L., Pohlit, H., Trau, D. & Tenje, M. (2018). Production of hyaluronic acid-acrylamide microgels as potential cell culture scaffolds. In: Micronano System Workshop, May 13-15, 2018: Book of Abstracts. Paper presented at Micronano System Workshop, Aalto University, Espoo, Finland, May 13th to 18th, 2018. (pp. 24-24).
Open this publication in new window or tab >>Production of hyaluronic acid-acrylamide microgels as potential cell culture scaffolds
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2018 (English)In: Micronano System Workshop, May 13-15, 2018: Book of Abstracts, 2018, p. 24-24Conference paper, Oral presentation with published abstract (Refereed)
Abstract [en]

Hyaluronic acid (HA) derived hydrogels give support and structure for cultured cells in 3D environments that better mimic in vivo conditions 1. Adequate diffusion of oxygen and nutrients however, is generally limited to a depth of 200 µm in bulk hydrogels 2, limiting their applicability to larger size constructs. Through droplet-based microfluidics we produced monodisperse HA-derived microgel droplets. Hyaluronic acid acrylamide (HA-am) was synthesized by partially modifying high molecular weight sodium hyaluronan with a N-(2-aminoethyl)acrylamide linker to a 20% degree.

Gel droplets were produced in a PDMS microfluidic device designed in a flow focusing geometry. In this setup polystyrene beads were added to simulate cell-encapsulation into a matrix that would better reflect in vivo conditions. The hydrogel precursor mixtures were prepared with 2% solution of HA-am and a photoinitiator with the addition of polystyrene beads (10µm in diameter) at a concentration of 10 million beads per milliliter. A fluorinated oil (Novec 7500, 3M) with 0.5% surfactant (PicoSurf 1) was used as the continuous phase. Highly monodisperse droplets of 151 µm in average diameter were produced and later polymerized by exposing to a long-wave UV light source (365 nm).  

We demonstrate that photocrosslinkable hydrogel droplets can be produced from HA-am. These microgels could enable the diffusion of nutrients and metabolites, while maintaining a size in which encapsulating sufficient cells to allow cell-cell interactions and proliferation would be possible.

[1]         J. A. Burdick and G. D. Prestwich, Adv. Mater., 2011, 23, 41–56.

[2]         H. Huang, Y. Yu, Y. Hu, X. He, O. Berk Usta and M. L. Yarmush, Lab Chip, 2017, 17, 1913–1932.

National Category
Engineering and Technology
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
urn:nbn:se:uu:diva-357608 (URN)
Conference
Micronano System Workshop, Aalto University, Espoo, Finland, May 13th to 18th, 2018.
Available from: 2018-08-17 Created: 2018-08-17 Last updated: 2018-10-19Bibliographically approved
Carter, S.-S., Atif, A., Lanekoff, I., Tenje, M. & Mestres, G. (2018). Tailoring the biocompatibility of the elastomer PDMS for on-chip applications. In: : . Paper presented at Scandinavian Society for Biomaterials.
Open this publication in new window or tab >>Tailoring the biocompatibility of the elastomer PDMS for on-chip applications
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2018 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Medical Materials
Identifiers
urn:nbn:se:uu:diva-353152 (URN)
Conference
Scandinavian Society for Biomaterials
Funder
Swedish Research Council Formas, 2016-00781Swedish Research Council, 2017-05051Knut and Alice Wallenberg Foundation, WAF 2016-0112
Available from: 2018-06-11 Created: 2018-06-11 Last updated: 2018-06-19
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-1264-1337

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