Lab-on-a-chip for drug development

Weigl, Bernhard H.; Bardell, Ron L.; Cabrera, Catherine

doi:10.1016/s0169-409x(02)00223-5

Cited by 435 publications

(254 citation statements)

References 170 publications

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“…Lab-on-a-Chip) is a key enabling technology for point-of-care diagnostics as it promises improvements over standard immunoassay formats in terms of speed, sensitivity and reagent consumption, and can potentially be highly automated [11][12][13][14][15][16][17][18][19][20] . A low-cost disposable microfluidic card could, in principle, carry out the necessary tests using a small patient sample and a scant amount of expensive reagents, (such as antibodies).…”

Section: Microfluidics (And Its Integration Into What Is Known Asmentioning

confidence: 99%

Concentration Gradient Immunoassay. 1. An Immunoassay Based on Interdiffusion and Surface Binding in a Microchannel

2007

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We describe a novel microfluidic immunoassay method based on the diffusion of a small molecule analyte into a parallel-flowing stream containing cognate antibody. This interdiffusion results in a steady-state gradient of antibody binding site occupancy transverse to convective flow. In contrast to the diffusion immunoassay (Hatch et al. Nature Biotechnology,19:461−465 (2001)), this antibody occupancy gradient is interrogated by a sensor surface coated with a functional analog of the analyte. Antibodies with at least one unoccupied binding site may specifically bind to this functionalized surface, leading to a quantifiable change in surface coverage by the antibody. SPR imaging is used to probe the spatial distribution of antibody binding to the surface and, therefore, the outcome of the assay. We show that the pattern of antibody binding to the SPR sensing surface correlates with the concentration of a model analyte (phenytoin) in the sample stream. Using an inexpensive disposable microfluidic device, we demonstrate assays for phenytoin ranging in concentration from 75 to 1000 nM in phosphate buffer. At a total volumetric flow rate of 90 nL/sec, the assays are complete within 10 minutes. Inclusion of an additional flow stream on the side of the antibody stream opposite to that of the sample enables simultaneous calibration of the assay. This assay method is suitable for rapid quantitative detection of low-molecular weight analytes for point-of-care diagnostic instrumentation.

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Section: Microfluidics (And Its Integration Into What Is Known Asmentioning

confidence: 99%

Concentration Gradient Immunoassay. 1. An Immunoassay Based on Interdiffusion and Surface Binding in a Microchannel

2007

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“…The creation and integration of these components represents a more substantial problem than it might seem, but the development of new microfluidic elements, and means to incorporate them into devices, are proceeding. Systems for bioanalysis and separation, [1][2][3] or high-throughput screening 4,5 are already available. We are especially interested in devices to be used in resource poor environments-e.g., in healthcare in developing countries, by first responders and the military, and in analogous problems-where portability and ruggedness are key concerns.…”

Section: Introductionmentioning

confidence: 99%

Mixing with bubbles: a practical technology for use with portable microfluidic devices

et al. 2006

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This paper demonstrates a methodology for micromixing that is sufficiently simple that it can be used in portable microfluidic devices. It illustrates the use of the micromixer by incorporating it into an elementary, portable microfluidic system that includes sample introduction, sample filtration, and valving. This system has the following characteristics: (i) it is powered with a single hand-operated source of vacuum, (ii) it allows samples to be loaded easily by depositing them into prefabricated wells, (iii) the samples are filtered in situ to prevent clogging of the microchannels, (iv) the structure of the channels ensure mixing of the laminar streams by interaction with bubbles of gas introduced into the channels, (v) the device is prepared in a single-step soft-lithographic process, and (vi) the device can be prepared to be resistant to the adsorption of proteins, and can be used with or without surface-active agents.We fabricated the device (Figs. 1a) in a polydimethylsiloxane (PDMS) slab sealed to a PDMS substrate. We chose to use PDMS because it is the most useful material for testing concepts in microfluidics, and because it is easily coupled with

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“…addressable delivery systems for charged biomolecules. We envisage that such ionic circuits will have impact in various fields including sensors 25 , lab-on-a-chip 26 , drug delivery 27 and electrochemical components 28 .…”

mentioning

confidence: 99%

Toward Complementary Ionic Circuits: The npn Ion Bipolar Junction Transistor

2011

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Many biomolecules are charged and may therefore be transported with ionic currents. As a step toward addressable ionic delivery circuits, we report on the development of a npn ion bipolar junction transistor (npn-IBJT) as an active control element of anionic currents in general, and specifically, demonstrate actively modulated delivery of the neurotransmitter glutamic acid. The functional materials of this transistor are ion exchange layers and conjugated polymers. The npn-IBJT shows stable transistor characteristics over extensive time of operation and ion current switch times below 10 s. Our results promise complementary chemical circuits similar to the electronic equivalence, which has proven invaluable in conventional electronic applications.

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Lab-on-a-chip for drug development

Cited by 435 publications

References 170 publications

Concentration Gradient Immunoassay. 1. An Immunoassay Based on Interdiffusion and Surface Binding in a Microchannel

Concentration Gradient Immunoassay. 1. An Immunoassay Based on Interdiffusion and Surface Binding in a Microchannel

Mixing with bubbles: a practical technology for use with portable microfluidic devices

Toward Complementary Ionic Circuits: The npn Ion Bipolar Junction Transistor

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