| 1. |
- Decrop, Deborah, et al.
(författare)
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Single-step imprinting of femtoliter microwell arrays allows digital bioassays with attomolar limit of detection
- 2017
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 9:12, s. 10418-10426
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Tidskriftsartikel (refereegranskat)abstract
- Bead-based microwell array technology is growing as an ultrasensitive target detection tool. However, dissemination of the technology and its commercial use are hampered by current fabrication methods for hydrophilic-in-hydrophobic microwell arrays, which are either expensive or labour-intensive to manufacture, or which results in low bead seeding efficiencies. In this paper, we present a novel single-step manufacturing method for imprinting cheap and disposable hydrophilic-in-hydrophobic microwell arrays suitable for single-molecule detection. Single-step imprinting of hydrophilic-in-hydrophobic microwell arrays is made possible using an innovative surface energy replication approach by means of a hydrophobic thiol-ene polymer formulation. In this polymer, hydrophobic-moiety-containing monomers self-assemble against the hydrophobic surface of the imprinting stamp, which results in a hydrophobic replica surface after polymerization. After removing the stamp, hydrophilic wells are obtained with the well bottoms consisting of glass substrate. We demonstrate that the hydrophilic-in-hydrophobic imprinted microwell arrays enable successful and efficient self-assembly of individual water droplets and seeding of magnetic beads with loading efficiencies up to 96%. We also demonstrate the suitability of the microwell arrays for the isolation and detection of single-molecules achieving a limit of detection of 17.4 aM when performing a streptavidin-biotin binding assay. The ease of manufacturing demonstrated here is expected to allow translation of digital microwell array technology towards diagnostic applications.
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| 2. |
- Gylfason, Kristinn B., 1978-, et al.
(författare)
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Integration of polymer based microfluidics with silicon photonics for biosensing applications
- 2015
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We present a novel integration method for packaging silicon photonic sensors with polymer microfluidics, designed to be suitable for wafer-level production. The method addresses the previously unmet manufacturing challenges of matching the microfluidic footprint area to that of the photonics, and of robust bonding of microfluidic layers to biofunctionalized surfaces. We demonstrate the fabrication, in a single step, of a microfluidic layer in the recently introduced OSTE polymer, and the subsequent unassisted dry bonding of the microfluidic layer to a grating coupled silicon photonic ring resonator sensor chip. The microfluidic layer features photopatterned through holes (vias) for optical fiber probing and fluid connections, as well as molded microchannels and tube connectors, and is manufactured and subsequently bonded to a silicon sensor chip in less than 10 minutes. Combining this new microfluidic packaging method with photonic waveguide surface gratings for light couplin g allows matching the size scale of microfluidics to that of current silicon photonic biosensors.
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| 3. |
- Kemas, Aurino M., et al.
(författare)
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Insulin-dependent glucose consumption dynamics in 3D primary human liver cultures measured by a sensitive and specific glucose sensor with nanoliter input volume
- 2021
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Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 35:3
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Tidskriftsartikel (refereegranskat)abstract
- The liver plays a central role in glucose homeostasis and hepatic insulin resistance constitutes a key feature of type 2 diabetes. However, platforms that accurately mimic human hepatic glucose disposition and allow for rapid and scalable quantification of glucose consumption dynamics are lacking. Here, we developed and optimized a colorimetric glucose assay based on the glucose oxidase-peroxidase system and demonstrate that the system can monitor glucose consumption in 3D primary human liver cell cultures over multiple days. The system was highly sensitive (limit of detection of 3.5 mu M) and exceptionally accurate (R-2 = 0.999) while requiring only nanoliter input volumes (250 nL), enabling longitudinal profiling of individual liver microtissues. By utilizing a novel polymer, off-stoichiometric thiol-ene (OSTE), and click-chemistry based on thiol-Michael additions, we furthermore show that the assay can be covalently bound to custom-build chips, facilitating the integration of the sensor into microfluidic devices. Using this system, we find that glucose uptake of our 3D human liver cultures closely resembles human hepatic glucose uptake in vivo as measured by euglycemic-hyperinsulinemic clamp. By comparing isogenic insulin-resistant and insulin-sensitive liver cultures we furthermore show that insulin and extracellular glucose levels account for 55% and 45% of hepatic glucose consumption, respectively. In conclusion, the presented data show that the integration of accurate and scalable nanoliter glucose sensors with physiologically relevant organotypic human liver models enables longitudinal profiling of hepatic glucose consumption dynamics that will facilitate studies into the biology and pathobiology of glycemic control, as well as antidiabetic drug screening.
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| 4. |
- Lobov, Gleb, et al.
(författare)
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Electro-optical effects of high aspect ratio P3HT nanofibers colloid in polymer micro-fluid cells
- 2017
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Ingår i: Optics Letters. - : OSA Publishing. - 0146-9592 .- 1539-4794. ; 42:11, s. 2157-2160
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Tidskriftsartikel (refereegranskat)abstract
- This Letter reports the electro-optical (EO) effect of Poly(3-hexylthiophene-2,5-diyl) (P3HT) nanofibers colloid in a polymer micro-fluidic EO cell. P3HT nanofibers are high aspect ratio semiconducting nanostructures, and can be collectively aligned by an external alternating electric field. Optical transmission modulated by the electric field is a manifestation of the electro-optical effect due to high inner crystallinity of P3HT nanofibers. According to our results, the degree of alignment reaches a maximum at 0.6 V/μm of electric field strength, implying a big polarizability value due to geometry and electrical properties of P3HT nanofibers. We believe that one-dimensional crystalline organic nanostructures have a large potential in EO devices due to their significant anisotropy, wide variety of properties, low actuation voltages, and opportunity to be tailored via adjustment of the fabrication process.
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| 5. |
- Marinins, Aleksandrs, et al.
(författare)
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Light Converting Polymer/Si Nanocrystal Composites with Stable 60-70% Quantum Efficiency and their Glass Laminates
- 2017
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 9:36, s. 30267-30272
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Tidskriftsartikel (refereegranskat)abstract
- Thiol-ene polymer/Si nanocrystal bulk hybrids were synthesized from alkyl-passivated Si nanocrystal (Si NC) toluene solutions. Radicals in the polymer provided a co-passivation of “dark” Si NCs, making them optically active and leading to a substantial ensemble quantum yield increase. Optical stability over several months was confirmed. The presented materials exhibit the highest photoluminescence quantum yield (~65%) of any solid-state Si NC hybrid reported to date. The broad tunability of thiol-ene polymer reactivity provides facile glass integration, as demonstrated by a laminated structure. This, together with extremely fast polymerization, makes the demonstrated hybrid material a promising candidate for light converting applications.
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| 6. |
- Rajabi, Mina, et al.
(författare)
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Flexible and Stretchable Microneedle Patches with Integrated Rigid Stainless Steel Microneedles for Transdermal Biointerfacing
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- This paper demonstrates flexible and stretchable microneedle patches that combine soft and flexible base substrates with hard and sharp stainless steel microneedles. An elastomeric polymer base enables conformal contact between the microneedle patch and the complex topography and texture of the underlying skin, while robust and sharp stainless steel microneedles reliably pierce the outer layers of the skin. The flexible microneedle patches have been realized by magnetically assembling short stainless steel microneedles into a flexible polymer supporting base. In our experimental investigation, the microneedle patches were applied to human skin and an excellent adaptation of the patch to the wrinkles and deformations of the skin was verified, while at the same time the microneedles reliably penetrate the surface of the skin. The unobtrusive flexible and stretchable microneedle patches have great potential for transdermal biointerfacing in a variety of emerging applications such as transdermal drug delivery, bioelectric treatments and wearable bio-electronics for health and fitness monitoring.
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| 7. |
- Sandström, Niklas, et al.
(författare)
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Batch fabrication of polymer microfluidic cartridges for QCM sensor packaging by direct bonding
- 2017
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Ingår i: Journal of Micromechanics and Microengineering. - : IOP Publishing. - 0960-1317 .- 1361-6439. ; 27:12
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Tidskriftsartikel (refereegranskat)abstract
- Quartz crystal microbalance (QCM) sensing is an established technique commonly used in laboratory based life-science applications. However, the relatively complex, multi-part design and multi-step fabrication and assembly of state-of-the-art QCM cartridges makes them unsuited for disposable applications such as point-of-care (PoC) diagnostics. In this work, we present the uncomplicated manufacturing of QCMs in polymer microfluidic cartridges. Our novel approach comprises two key innovations: the batch reaction injection molding of microfluidic parts; and the integration of the cartridge components by direct, unassisted bonding. We demonstrate molding of batches of 12 off-stoichiometry thiol-ene epoxy polymer (OSTE+) polymer parts in a single molding cycle using an adapted reaction injection molding process; and the direct bonding of the OSTE+ parts to other OSTE+ substrates, to printed circuit boards, and to QCMs. The microfluidic QCM OSTE+ cartridges were successfully evaluated in terms of liquid sealing as well as electrical properties, and the sensor performance characteristics are on par with those of commercially available QCM biosensor cartridge.
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| 8. |
- Sandström, Niklas, 1981-, et al.
(författare)
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ONE STEP INTEGRATION OF GOLD COATED SENSORS WITH OSTE POLYMER CARTRIDGES BY LOW TEMPERATURE DRY BONDING
- 2011
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Ingår i: 16th IEEE International Conference on Solid-State Sensors, Actuators and Microsystems (IEEE TRANSDUCERS 2011). - : IEEE conference proceedings. - 9781457701573 ; , s. 2778-2781
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Konferensbidrag (refereegranskat)abstract
- We propose and demonstrate a novel one step method to integrate gold coated sensors with cartridges by dry covalent bonding. The cartridges are replica molded in an UV-curable off-stoichiometry thiol-ene (OSTE) polymer, featuring an excess of thiol functional groups that covalently bond to the surface of gold coated sensors upon contact. The method is demonstrated by the integration of a gold coated quartz crystal to a microfludic OSTE cartridge. The resulting bond interface is shown to be completely homogenous and void free and the package is tested successfully to a differential pressure of up to 2 bars. The performance of the biosensor chip is evaluated by measuring the unspecific binding of 0.5% albumin, resulting in a total frequency drop 205 Hz. This approach delivers a simple but rapid high quality integration aiming for the production of robust, low cost and disposable biosensor chips
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| 9. |
- Sandström, Niklas, 1981-, et al.
(författare)
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Reaction injection molding and direct covalent bonding of OSTE+ polymer microfluidic devices
- 2015
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Ingår i: Journal of Micromechanics and Microengineering. - : Institute of Physics (IOP). - 0960-1317 .- 1361-6439. ; 25:7
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Tidskriftsartikel (refereegranskat)abstract
- In this article, we present OSTE+RIM, a novel reaction injection molding (RIM) process that combines the merits of off-stoichiometric thiol–ene epoxy (OSTE+) thermosetting polymers with the fabrication of high quality microstructured parts. The process relies on the dual polymerization reactions of OSTE+ polymers, where the first curing step is used in OSTE+RIM for molding intermediately polymerized parts with well-defined shapes and reactive surface chemistries. In the facile back-end processing, the replicated parts are directly and covalently bonded and become fully polymerized using the second curing step, generating complete microfluidic devices. To achieve unprecedented rapid processing, high replication fidelity and low residual stress, OSTE+RIM uniquely incorporates temperature stabilization and shrinkage compensation of the OSTE+ polymerization during molding. Two different OSTE+ formulations were characterized and used for the OSTE+RIM fabrication of optically transparent, warp-free and natively hydrophilic microscopy glass slide format microfluidic demonstrator devices, featuring a storage modulus of 2.3 GPa and tolerating pressures of at least 4 bars.
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| 10. |
- Shafagh, Reza Zandi, et al.
(författare)
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Bioengineered Pancreas–Liver Crosstalk in a Microfluidic Coculture Chip Identifies Human Metabolic Response Signatures in Prediabetic Hyperglycemia
- 2022
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Ingår i: Advanced Science. - : Wiley. - 2198-3844. ; , s. 2203368-2203368
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Tidskriftsartikel (refereegranskat)abstract
- Aberrant glucose homeostasis is the most common metabolic disturbance affecting one in ten adults worldwide. Prediabetic hyperglycemia due to dysfunctional interactions between different human tissues, including pancreas and liver, constitutes the largest risk factor for the development of type 2 diabetes. However, this early stage of metabolic disease has received relatively little attention. Microphysiological tissue models that emulate tissue crosstalk offer emerging opportunities to study metabolic interactions. Here, a novel modular multitissue organ-on-a-chip device is presented that allows for integrated and reciprocal communication between different 3D primary human tissue cultures. Precisely controlled heterologous perfusion of each tissue chamber is achieved through a microfluidic single “synthetic heart” pneumatic actuation unit connected to multiple tissue chambers via specific configuration of microchannel resistances. On-chip coculture experiments of organotypic primary human liver spheroids and intact primary human islets demonstrate insulin secretion and hepatic insulin response dynamics at physiological timescales upon glucose challenge. Integration of transcriptomic analyses with promoter motif activity data of 503 transcription factors reveals tissue-specific interacting molecular networks that underlie β-cell stress in prediabetic hyperglycemia. Interestingly, liver and islet cultures show surprising counter-regulation of transcriptional programs, emphasizing the power of microphysiological coculture to elucidate the systems biology of metabolic crosstalk.
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