Rapid, femtomolar bioassays in complex matrices combining microfluidics and magnetoelectronics

Mulvaney, Shawn P.; Cole, Christina L.; Kniller, Matthew D.; Malito, Michael; Tamanaha, Cy R.; Rife, J. C.; Stanton, Mike; Whitman, L. J.

doi:10.1016/j.bios.2007.03.029

Cited by 118 publications

(118 citation statements)

References 39 publications

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“…2B). Thus, continuous microfluidic washing appears to be significantly more effective at removing nonspecific phage, presumably by eliminating rebinding events (33)(34)(35)(36). This finding is further supported by the work of Yuan et al which used flow-based phage selection in an surface plasmon resonance (SPR) instrument (37).…”

Section: Resultsmentioning

confidence: 77%

Selection of phage-displayed peptides on live adherent cells in microfluidic channels

Wang

Teesalu

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Affinity reagents that bind to specific molecular targets are an essential tool for both diagnostics and targeted therapeutics. There is a particular need for advanced technologies for the generation of reagents that specifically target cell-surface markers, because transmembrane proteins are notoriously difficult to express in recombinant form. We have previously shown that microfluidics offers many advantages for generating affinity reagents against purified protein targets, and we have now significantly extended this approach to achieve successful in vitro selection of T7 phagedisplayed peptides that recognize markers expressed on live, adherent cells within a microfluidic channel. As a model, we have targeted neuropilin-1 (NRP-1), a membrane-bound receptor expressed at the surface of human prostate carcinoma cells that plays central roles in angiogenesis, cell migration, and invasion. We show that, compared to conventional biopanning methods, microfluidic selection enables more efficient discovery of peptides with higher affinity and specificity by providing controllable and reproducible means for applying stringent selection conditions against minimal amounts of target cells without loss. Using our microfluidic system, we isolate peptide sequences with superior binding affinity and specificity relative to the well known NRP-1-binding RPARPAR peptide. As such microfluidic systems can be used with a wide range of biocombinatorial libraries and tissue types, we believe that our method represents an effective approach toward efficient biomarker discovery from patient samples.

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Section: Resultsmentioning

confidence: 77%

Selection of phage-displayed peptides on live adherent cells in microfluidic channels

Wang

Teesalu

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…1 is a critical technology for an extremely broad range of biomedical applications including tissue engineering, 2,3 drug discovery, 4 point-of-care diagnostics and pathogen detection in both developed and developing countries, [5][6][7][8] and cancer screening using approaches such as cell identification, 9 and protein, [10][11][12][13] DNA, 14 and micro-RNA 15,16 biomarkers. Microfluidic device prototyping for proof-of-principle demonstration typically utilizes hot embossed or injection molded plastics 1,17 or polydimethylsiloxane (PDMS).…”

Section: Microfluidicsmentioning

confidence: 99%

3D printed microfluidic devices with integrated valves

2015

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We report the successful fabrication and testing of 3D printed microfluidic devices with integrated membrane-based valves. Fabrication is performed with a low-cost commercially available stereolithographic 3D printer. Horizontal microfluidic channels with designed rectangular cross sectional dimensions as small as 350 μm wide and 250 μm tall are printed with 100% yield, as are cylindrical vertical microfluidic channels with 350 μm designed (210 μm actual) diameters. Based on our previous work [Rogers et al., Anal. Chem. 83, 6418 (2011)], we use a custom resin formulation tailored for low non-specific protein adsorption. Valves are fabricated with a membrane consisting of a single build layer. The fluid pressure required to open a closed valve is the same as the control pressure holding the valve closed. 3D printed valves are successfully demonstrated for up to 800 actuations.

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“…The device was ultimately successful in eliminating multiple microdrop interference and can be applied in future digital microfluidic applications requiring small electrode sizes or scaling to massively parallel architectures. Potential applications of this device include bioassay processes [28], highly parallel planar mixing processes [29], DNA analyses [6], and glucose monitoring systems [30].…”

Section: Resultsmentioning

confidence: 99%

Nonlinear Dual-Phase Multiplexing in Digital Microfluidic Architectures

et al. 2011

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A 16 × 16 digital microfluidic multiplexer is demonstrated. The device makes use of dual-phase AC activation in a bi-layered electrode structure for actuating microdrops independently. A switching arrangement is employed to localize two out-of-phase AC waveforms in one overlapped region of the two-dimensional multiplexer grid. The superimposed AC waveforms overcome the threshold voltage for motion of a local microdrop. The demonstrated dual-phase activation and nonlinear threshold-based motion overcomes the previously-reported microdrop interference effect, as it successfully actuates individual microdrops in systems with multiple neighbouring microdrops. The device is demonstrated with an integrated centre-tap transformer using a 10.0 V rms input voltage and minimal power consumption.

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Rapid, femtomolar bioassays in complex matrices combining microfluidics and magnetoelectronics

Cited by 118 publications

References 39 publications

Selection of phage-displayed peptides on live adherent cells in microfluidic channels

Selection of phage-displayed peptides on live adherent cells in microfluidic channels

3D printed microfluidic devices with integrated valves

Nonlinear Dual-Phase Multiplexing in Digital Microfluidic Architectures

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