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Fornell, A., Söderbäck, P., Liu, Z., Moreira, M. & Tenje, M. (2020). Fabrication of Silicon Microfluidic Chips for Acoustic Particle Focusing Using Direct Laser Writing. Micromachines, 11(2), Article ID 113.
Open this publication in new window or tab >>Fabrication of Silicon Microfluidic Chips for Acoustic Particle Focusing Using Direct Laser Writing
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2020 (English)In: Micromachines, ISSN 2072-666X, E-ISSN 2072-666X, Vol. 11, no 2, article id 113Article in journal (Refereed) Published
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.

National Category
Materials Engineering Other Physics Topics
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
urn:nbn:se:uu:diva-402902 (URN)10.3390/mi11020113 (DOI)
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

Anna Fornell and Per Söderbäck contributed equally to this work.

Available from: 2020-01-21 Created: 2020-01-21 Last updated: 2020-01-21Bibliographically approved
Liu, Z., Fornell, A. & Tenje, M. (2019). A continuous on-chip droplet washing platform with high bead recovery by acoustofluidics. In: : . Paper presented at Acoustofluidics 2019, 26-28 August 2019, Enschede, Netherlands.
Open this publication in new window or tab >>A continuous on-chip droplet washing platform with high bead recovery by acoustofluidics
2019 (English)Conference paper, Poster (with or without abstract) (Other academic)
Abstract [en]

Acoustofluidics is a promising technology for manipulation of fluids and particles in microchannels, and the technology has the ability to sort beads and cells in continuous flow with very high efficiency. Recently acoustofluidics has also been applied in segmental flow for positioning beads inside droplets. Compared with single-phase systems, droplet microfluidics has the advantages of faster reactions, lower cross-contamination and higher throughput. Moreover, the small size of the droplets makes them ideal as cultivation and reaction vials for single cell analysis. However, as the droplets are so small one challenge is to wash the droplets before image analysis. P. Mary et al. developed a microfluidic platform for droplet wash, whichis based on electrocoalescence and droplet break-ups with equal volume. The background noise was decreased significantly, however the recovery of the encapsulated cells was low. Alternative solutions have been presented by H. Lee et al. and S.R. Doonan et al. but as the bead recovery is controlled via magnetophoresis, the technology is only applicable to magnetic samples. Here we present a droplet microfluidic platform that enables background dilution with high bead recovery in a label-free manner using acoustophoresis.

Keywords
Droplet dilution, acoustophoresis, pico-injection, microfluidics, electrocoalescence
National Category
Medical Laboratory and Measurements Technologies
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
urn:nbn:se:uu:diva-392166 (URN)
Conference
Acoustofluidics 2019, 26-28 August 2019, Enschede, Netherlands
Available from: 2019-08-30 Created: 2019-08-30 Last updated: 2019-08-30Bibliographically approved
Tenje, M. (2019). Acoustic particle manipulation in droplet microfluidics. In: : . Paper presented at Acoustofluidics 2019, 25-28 August 2019, Enschede, Netherlands.
Open this publication in new window or tab >>Acoustic particle manipulation in droplet microfluidics
2019 (English)Conference paper, Oral presentation with published abstract (Other academic)
National Category
Medical Biotechnology
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
urn:nbn:se:uu:diva-398396 (URN)
Conference
Acoustofluidics 2019, 25-28 August 2019, Enschede, Netherlands
Available from: 2019-12-05 Created: 2019-12-05 Last updated: 2019-12-09Bibliographically approved
Fornell, A., Johannesson, C., Searle, S., Happstadius, A., Nilsson, J. & Tenje, M. (2019). Acoustic trapping: a non-contact method to handle cell-laden hydrogel droplets in a microchannel. In: : . Paper presented at 2nd European Organ-on-Chip Conference (EUROoC 2019). 2-3 July 2019, Graz, Austria.
Open this publication in new window or tab >>Acoustic trapping: a non-contact method to handle cell-laden hydrogel droplets in a microchannel
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2019 (English)Conference paper, Oral presentation with published abstract (Other academic)
National Category
Other Medical Engineering
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
urn:nbn:se:uu:diva-390927 (URN)
Conference
2nd European Organ-on-Chip Conference (EUROoC 2019). 2-3 July 2019, Graz, Austria
Available from: 2019-08-15 Created: 2019-08-15 Last updated: 2019-08-20Bibliographically approved
Fornell, A., Johannesson, C., Searle, S. S., Happstadius, A., Nilsson, J. & Tenje, M. (2019). An acoustofluidic platform for non-contact trapping of cell-laden hydrogel droplets compatible with optical microscopy. Biomicrofluidics, 13, Article ID 044101.
Open this publication in new window or tab >>An acoustofluidic platform for non-contact trapping of cell-laden hydrogel droplets compatible with optical microscopy
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2019 (English)In: Biomicrofluidics, ISSN 1932-1058, E-ISSN 1932-1058, Vol. 13, article id 044101Article in journal (Refereed) Published
Abstract [en]

Production of cell-laden hydrogel droplets as miniaturized niches for 3D cell culture provides a new route for cell-based assays. Such production can be enabled by droplet microfluidics and here we present a droplet trapping system based on bulk acoustic waves for handling hydrogel droplets in a continuous flow format. The droplet trapping system consists of a glass capillary equipped with a small piezoelectric transducer. By applying ultrasound (4 MHz), a localized acoustic standing wave field is generated in the capillary, trapping the droplets in a well-defined cluster above the transducer area. The results show that the droplet cluster can be retained at flow rates of up to 76 mu l/min, corresponding to an average flow speed of 3.2 mm/s. The system allows for important operations such as continuous perfusion and/or addition of chemical reagents to the encapsulated cells with in situ optical access. This feature is demonstrated by performing on-chip staining of the cell nuclei. The key advantages of this trapping method are that it is label-free and gentle and thus well-suited for biological applications. Moreover, the droplets can easily be released on-demand, which facilitates downstream analysis. It is envisioned that the presented droplet trapping system will be a valuable tool for a wide range of multistep assays as well as long-term monitoring of cells encapsulated in gel-based droplets.

National Category
Other Chemical Engineering
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
urn:nbn:se:uu:diva-392104 (URN)10.1063/1.5108583 (DOI)000483884200007 ()31312286 (PubMedID)
Funder
Swedish Research CouncilThe Crafoord FoundationStiftelsen Olle Engkvist ByggmästareSwedish Foundation for Strategic Research
Available from: 2019-08-29 Created: 2019-08-29 Last updated: 2019-10-17Bibliographically approved
Blasi Romero, A., Nguyen, H., Barbe, L., Tenje, M. & Mestres, G. (2019). Development and validation of a reusable microfluidic system for the evaluation of biomaterials’ biological properties. In: : . Paper presented at 2nd European Organ-on-Chip Conference (EUROoC 2019), 2-3 July 2019, Graz, Austria.
Open this publication in new window or tab >>Development and validation of a reusable microfluidic system for the evaluation of biomaterials’ biological properties
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2019 (English)Conference paper, Poster (with or without abstract) (Other academic)
Keywords
Biomaterials, biomaterials-on-chip, microfluidics
National Category
Medical Materials
Identifiers
urn:nbn:se:uu:diva-392966 (URN)
Conference
2nd European Organ-on-Chip Conference (EUROoC 2019), 2-3 July 2019, Graz, Austria
Available from: 2019-09-11 Created: 2019-09-11 Last updated: 2019-09-16Bibliographically approved
Liu, Z., Fornell, A. & Tenje, M. (2019). Droplet Dilution Unit Operation Including Bead Washing Using Integrated Acoustophoresis. In: : . Paper presented at The 20th International Conference on Solid-State Sensors, Actuators and Microsystems (Transducers 2019 - EUROSENSORS XXXIII), 23-27 June 2019, Berlin, Germany.
Open this publication in new window or tab >>Droplet Dilution Unit Operation Including Bead Washing Using Integrated Acoustophoresis
2019 (English)Conference paper, Poster (with or without abstract) (Other academic)
Abstract [en]

This paper presents a microfluidic platform for on-chip droplet dilution where the bead recovery also can be controlled. The droplets containing 10 µm polystyrene beads can be diluted with high bead recovery. This platform involves 5 steps for on-chip dilution of the droplets: droplet generation, bead focusing, droplet splitting, pico-injection and serpentine mixing. Background signal in the droplets is significantly reduced with maintained bead recovery by this on-chip dilution method. The technology is applicable to many types of samples and does not require any labelling of the bioparticles.

Keywords
Droplet dilution, acoustophoresis, pico-injection, microfluidics, electrocoalescence
National Category
Engineering and Technology Embedded Systems
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
urn:nbn:se:uu:diva-390848 (URN)
Conference
The 20th International Conference on Solid-State Sensors, Actuators and Microsystems (Transducers 2019 - EUROSENSORS XXXIII), 23-27 June 2019, Berlin, Germany
Available from: 2019-08-15 Created: 2019-08-15 Last updated: 2019-08-26Bibliographically approved
Atif, A. R., Pujari-Palmer, M., Tenje, M. & Mestres, G. (2019). Evaluation of Ionic Interactions of Bone Cement-on-Chip. In: : . Paper presented at 1st European Organ-on-Chips Society Conference, Graz, July 2-3, 2019.
Open this publication in new window or tab >>Evaluation of Ionic Interactions of Bone Cement-on-Chip
2019 (English)Conference paper, Poster (with or without abstract) (Other academic)
Abstract [en]

INTRODUCTION: Biomaterials are synthetic materials that can be incorporated into the body to replace an impaired physiological function. Apatite calcium phosphate cements (CPCs), used for bone regeneration, give calcium-deficient hydroxyapatite (CDHA) as an end-product after a dissolution-precipitation reaction during fabrication. CDHA has a tendency to uptake calcium and release phosphate into cell culture medium. Potentially, this leads to depletion of calcium ions in solution, which can be detrimental to cell survival. The aim of this work is to embed CDHA in a microfluidic system and evaluate ion exchange at different flow rates.

METHODS: CPC paste was cast into a 0.8mm pocket within a Polydimethylsiloxane (PDMS, cured at 60°C for 2h) mould. CPCs were set in 0.9% w/v NaCl at 37°C for 10 days resulting in CDHA. The PDMS containing the CDHA was then bonded to glass, leaving a 0.5mm channel gap. Minimum Essential Media (MEM, 1ml) was pumped through the channel at low (2µl/min), medium (8µl/min) and high (14µl/min) flow rates. A CDHA disc (ø=15mm, h=2mm) was immersed in MEM (1ml) at static conditions (0µl/min) for 24h. Stock Media was taken as control. Calcium and phosphorus concentrations were analysed using Inductively Coupled Plasma Optical Emission Spectroscopy.

RESULTS & CONCLUSIONS: CDHA was successfully embedded in a microfluidic chip (Fig. 1A). Observed [Ca] and [P] levels were closer to levels in stock MEM at higher flow rates (Fig. 1B). We anticipate that osteoblast viability will improve when grown under flow, as opposed to static conditions, due to continuous replenishment of cell medium.

National Category
Medical Materials
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
urn:nbn:se:uu:diva-393088 (URN)
Conference
1st European Organ-on-Chips Society Conference, Graz, July 2-3, 2019
Funder
Swedish Research Council, 2017-05051Swedish Research Council Formas, 2016-00781Knut and Alice Wallenberg Foundation, 2016-0112Göran Gustafsson Foundation for Research in Natural Sciences and Medicine, 1841
Available from: 2019-09-16 Created: 2019-09-16 Last updated: 2019-09-16Bibliographically approved
Fornell, A., Liu, Z. & Tenje, M. (2019). Improved acoustic particle enrichment in droplets by optimising the droplet split design. In: : . Paper presented at Acoustofluidics 2019, 26-28 August 2019, Enschede, Netherlands.
Open this publication in new window or tab >>Improved acoustic particle enrichment in droplets by optimising the droplet split design
2019 (English)Conference paper, Oral presentation with published abstract (Other academic)
Abstract [en]

Droplet microfluidics has emerged as a valuable platform for miniaturisation of biological experiments on-chip. In droplet microfluidic chips monodisperse droplets containing cells or other bioparticles can be generated at high throughput, and each droplet can be used as an isolated reaction chamber for individual measurements. A general trend in droplet microfluidics is reducing the size of the droplets, but the challenge is maintaining the particles in the droplets after splitting. We have previously reported on an acoustofluidic chip where bulk acoustic waves were used to control particle positioning in a trident-shaped droplet split. However, the reported particle enrichment was modest (3-fold), and the aim of this study is to increase the particle enrichment by optimising the droplet split design. With our new optimised droplet split we show up to 16.7-fold particle enrichment with high particle recovery.

National Category
Medical Laboratory and Measurements Technologies
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
urn:nbn:se:uu:diva-392102 (URN)
Conference
Acoustofluidics 2019, 26-28 August 2019, Enschede, Netherlands
Available from: 2019-08-29 Created: 2019-08-29 Last updated: 2019-08-30Bibliographically approved
Werr, G., Khaji, Z., Ohlin, M., Andersson, M., Klintberg, L., Searle, S., . . . Tenje, M. (2019). Integrated thin film resistive sensors for in situ temperature measurements in an acoustic trap. Journal of Micromechanics and Microengineering, 29(9), Article ID 095003.
Open this publication in new window or tab >>Integrated thin film resistive sensors for in situ temperature measurements in an acoustic trap
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2019 (English)In: Journal of Micromechanics and Microengineering, ISSN 0960-1317, E-ISSN 1361-6439, Vol. 29, no 9, article id 095003Article in journal (Refereed) Published
Abstract [en]

This work presents an acoustic trap with integrated thin film sensors to monitor temperature variations during operation. The acoustic trap is wet-etched in glass with a thermally bonded glass lid and the thin-film sensors are integrated during fabrication. We evaluated the performance of the integrated temperature sensors and measured a temperature sensitivity of +/- 0.01 degrees C and confirmed that the read-out of the thin film sensors was not affected neither by the ionic conductivity of the solution nor the addition of microparticles into the acoustic trap. From the experiments we observed a temperature increase of the acoustic trap during operation as a result of the dissipative heating of the the piezoelectric element used to actuate the trap. We also showed that when external convective cooling was applied to the system, the temperature increase of the acoustic trap was higher than the temperature increase of the piezoelectric element itself. This shows the importance of using integrated temperature sensors in acoustic trapping to monitor the local environmental conditions.

Place, publisher, year, edition, pages
IOP PUBLISHING LTD, 2019
Keywords
acoustophoresis, integrated RTD, external TC, acoustic trap, glass chip
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:uu:diva-391278 (URN)10.1088/1361-6439/ab2ac8 (DOI)000476561400001 ()
Funder
Knut and Alice Wallenberg Foundation
Available from: 2019-08-22 Created: 2019-08-22 Last updated: 2019-08-22Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-1264-1337

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