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- Werr, Gabriel, 1991-, et al.
(author)
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Integrated thin film resistive sensors for in situ temperature measurements in an acoustic trap
- 2019
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In: Journal of Micromechanics and Microengineering. - : IOP PUBLISHING LTD. - 0960-1317 .- 1361-6439. ; 29:9, s. 140-141
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Journal article (peer-reviewed)abstract
- 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.
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| 2. |
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| 3. |
- Fornell, Anna, et al.
(author)
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An acoustofluidic platform for non-contact trapping of cell-laden hydrogel droplets compatible with optical microscopy
- 2019
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In: Biomicrofluidics. - : AIP Publishing. - 1932-1058. ; 13
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Journal article (peer-reviewed)abstract
- 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.
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| 4. |
- Fornell, Anna, et al.
(author)
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Trapping of Cell-Laden Hyaluronic Acid-Acrylamide Hydrogel Droplets using Bulk Acoustic Waves
- 2019
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In: 2019 20th International Conference on Solid-State Sensors, Actuators and Microsystems & Eurosensors XXXIII (TRANSDUCERS & EUROSENSORS XXXIII). - : IEEE. - 9781538681046 - 9781728120072 ; , s. 2352-2355
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Conference paper (peer-reviewed)abstract
- 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.
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| 6. |
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| 7. |
- Searle, Sean, 1991-, et al.
(author)
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Hyaluronic acid based hydrogel droplets: A potential injectable cell culture scaffold
- 2018
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Conference paper (other academic/artistic)abstract
- IntroductionCell 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 resultsHyaluronic 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. ConclusionHighly 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.
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| 8. |
- Searle, Sean, 1991-, et al.
(author)
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Production of hyaluronic acid-acrylamide microgels as potential cell culture scaffolds
- 2018
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In: Micronano System Workshop, May 13-15, 2018. ; , s. 24-24
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Conference paper (peer-reviewed)abstract
- 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.
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| 9. |
- Tenje, Maria, et al.
(author)
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A practical guide to microfabrication and patterning of hydrogels for biomimetic cell culture scaffolds
- 2020
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In: Organs-on-a-Chip. - The Netherlands : Elsevier. - 2666-1020. ; 2
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Research review (peer-reviewed)abstract
- This review article describes microfabrication techniques to define chemical, mechanical and structural patterns in hydrogels and how these can be used to prepare in vivo like, i.e. biomimetic, cell culture scaffolds. Hydrogels are attractive materials for 3D cell cultures as they provide ideal culture conditions and they are becoming more prominently used. Single material gels without any modifications do however have their limitation in use and much can be gained by in improving the in vivo resemblance of simple hydrogel cell culture scaffolds. This review article discusses the most commonly used cross-linking strategies used for hydrogel-based culture scaffolds and gives a brief introduction to microfabrication methods that can be used to define chemical, mechanical and structural patterns in hydrogels with micrometre resolution. The review article also describes a selection of literature references using these microfabrication techniques to prepare organ and disease models with controlled cell adhesion, proliferation and migration. It is intended to serve as an introduction to microfabrication of hydrogels and an inspiration for novel interdisciplinary research projects.
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| 10. |
- Wanselius, Marcus, et al.
(author)
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Microfluidics platform for studies of peptide - polyelectrolyte interaction
- 2022
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In: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 621
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Journal article (peer-reviewed)abstract
- Subcutaneous injection is one of the most common approaches for administering biopharmaceuticals unsuitable for oral delivery. However, there is a lack of methods to predict the behavior of biopharmaceuticals within the extracellular matrix of the subcutaneous tissue. In this work, we present a novel miniaturized microfluidic-based in vitro method able to investigate interactions between drug molecules and the polymers of the subcutaneous extracellular matrix. To validate the method, microgels consisting of, respectively, covalently cross-linked hy-aluronic acid, polyacrylic acid, and commercially available DC BeadTM, were exposed to three model substances: cytochrome C, protamine sulfate and amitriptyline hydrochloride. These components were chosen to include systems with widely different physiochemical properties (charge, size, self-assembly, etc.) The experimental results were compared with theoretical predictions from a gel model developed earlier. The results show that the method is suitable as a rapid screening method for automated, large-scale, probing of interactions between biopolymers and drug molecules, with small consumption of material.
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