A rapid diffusion immunoassay in a T-sensor

Hatch, Anson V.; Kamholz, Andrew Evan; Hawkins, Kenneth; Munson, Matthew; Schilling, Eric A.; Weigl, Bernhard H.; Yager, Paul

doi:10.1038/88135

Cited by 354 publications

(267 citation statements)

References 24 publications

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“…In the past, fluidic control included syringe pumps (11), hydrogel valves (12), gravity-driven pumps (13), evaporation-based pumps (14,15), acoustic pumps (16), gas-generationbased pumps (17,18), and centrifugal force in CD chips (19). Electrokinetic flow (20)(21)(22), thermopneumatic (23,24), pneumatic͞hydraulic (25), or mechanical (26,27) valves and pumps have a high degree of control, but require external connection lines to larger equipment for actuation.…”

mentioning

confidence: 99%

Computerized microfluidic cell culture using elastomeric channels and Braille displays

Zhu

Futai

et al. 2004

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

375

312

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Computer-controlled microfluidics would advance many types of cellular assays and microscale tissue engineering studies wherever spatiotemporal changes in fluidics need to be defined. However, this goal has been elusive because of the limited availability of integrated, programmable pumps and valves. This paper demonstrates how a refreshable Braille display, with its grid of 320 vertically moving pins, can power integrated pumps and valves through localized deformations of channel networks within elastic silicone rubber. The resulting computerized fluidic control is able to switch among: (i) rapid and efficient mixing between streams, (ii) multiple laminar flows with minimal mixing between streams, and (iii) segmented plug-flow of immiscible fluids within the same channel architecture. The same control method is used to precisely seed cells, compartmentalize them into distinct subpopulations through channel reconfiguration, and culture each cell subpopulation for up to 3 weeks under perfusion. These reliable microscale cell cultures showed gradients of cellular behavior from C2C12 myoblasts along channel lengths, as well as differences in cell density of undifferentiated myoblasts and differentiation patterns, both programmable through different flow rates of serumcontaining media. This technology will allow future microscale tissue or cell studies to be more accessible, especially for highthroughput, complex, and long-term experiments. The microfluidic actuation method described is versatile and computer programmable, yet simple, well packaged, and portable enough for personal use.pump ͉ valve ͉ bioreactor ͉ mixer ͉ perfusion A dvanced microfluidic cellular assays (1-6) and microscale tissue engineering studies (7-10) would benefit from robust and convenient methods to computer-control accurate spatiotemporal patterns of microfluidic flows in arrays of fluidic networks. In the past, fluidic control included syringe pumps (11), hydrogel valves (12), gravity-driven pumps (13), evaporation-based pumps (14, 15), acoustic pumps (16), gas-generationbased pumps (17, 18), and centrifugal force in CD chips (19). Electrokinetic flow (20-22), thermopneumatic (23, 24), pneumatic͞hydraulic (25), or mechanical (26, 27) valves and pumps have a high degree of control, but require external connection lines to larger equipment for actuation. A few fully integrated and self-packaged systems (23, 28) have been developed, but lack the reconfigurability inherent with numerous active valves and pumps.Here, we report a method to precisely control fluid flow inside elastomeric capillary networks by using multiple (tens to hundreds) computer-controlled, piezoelectric, movable pins. These pins are positioned as a grid on a refreshable Braille display (e.g., F. H. Papenmeier, Schwerte, Germany), which is a tactile device used by the visually impaired to read computer text. Each pin can act as a valve and be shifted upward to push against channels contained in silicone rubber and completely shut the channel. Three sequential valves of this...

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mentioning

confidence: 99%

Computerized microfluidic cell culture using elastomeric channels and Braille displays

Zhu

Futai

et al. 2004

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

375

312

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“…8,9 Adjacent flow streams translate by advection without significant mixing, and solutes in the adjacent streams only intermingle via the process of diffusion, which is therefore an especially important mechanism of particle transport on the microscale. 10,11 Volumes of fluid do not mix to any significant extent except by boundary diffusion around its borders and, if required, mixing of the solutes can be enhanced by the introduction of zig-zag channel geometries ("mixers"). 1,2 It is important to understand the intermixing process of biomolecules between liquid layers, of possibly different chemical constituency, as it has an impact on the effectiveness of assay-related activity, and consequently microfluidic device geometry design.…”

Section: Introductionmentioning

confidence: 99%

Spatially dependent diffusion coefficient as a model for pH sensitive microgel particles in microchannels

2016

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Solute transport and intermixing in microfluidic devices is strongly dependent on diffusional processes. Brownian Dynamics simulations of pressure-driven flow of model microgel particles in microchannels have been carried out to explore these processes and the factors that influence them. The effects of a pH-field that induces a spatial dependence of particle size and consequently the self-diffusion coefficient and system thermodynamic state were focused on. Simulations were carried out in 1D to represent some of the cross flow dependencies, and in 2D and 3D to include the effects of flow and particle concentration, with typical stripe-like diffusion coefficient spatial variations. In 1D, the mean square displacement and particle displacement probability distribution function agreed well with an analytically solvable model consisting of infinitely repulsive walls and a discontinuous pHprofile in the middle of the channel. Skew category Brownian motion and nonGaussian dynamics were observed, which follows from correlations of step lengths in the system, and can be considered to be an example of so-called "diffusing diffusivity." In Poiseuille flow simulations, the particles accumulated in regions of larger diffusivity and the largest particle concentration throughput was found when this region was in the middle of the channel. The trends in the calculated cross-channel diffusional behavior were found to be very similar in 2D and 3D. Published by AIP Publishing. [http://dx

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“…The T-mixer has been demonstrated as a tool for the measurements of diffusion coefficients, and as a platform for chemical assays, [18][19][20] as a diffusion based immunoassay. [21][22][23] Knight et al introduced a similar laminar flow mixer with three inlets (n ¼ 3) known as ''hydrodynamic focusing mixing''. 24 The buffer solutions from two symmetric orthogonal side channels focus the sample solution entering from the centre channel into a thin stream.…”

Section: Introductionmentioning

confidence: 99%

Sandwich mixer–reactor: influence of the diffusion coefficient and flow rate ratios

Abonnenc

Josserand

2009

Lab Chip

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A sandwich mixer consists of mixing two solutions in a channel, one central laminar flow being sandwiched between two outer flow solutions. The present numerical study considers the convectiondiffusion of two reacting species A and B, provided respectively by the two incoming solutions. The simulations show how the diffusion coefficient, flow rate and species concentration ratios influence, via the transversal diffusion length and reaction kinetics, the reaction extent at the end of the sandwich mixer. First, this extent can be enhanced up to 60% if the species with the lowest diffusion coefficient is located in the outer solutions where the flow velocity is small compared to that of the central part (higher residence time). Secondly, decreasing the outer flow rates (to confine the reaction close to the walls) and increasing the local concentration to keep the same flux ratio improve the extent by 300%.Comparison with a bi-lamination passive mixer, with an ideal mixer and an electro-osmotic driven flow mixer is presented. These conclusions are also demonstrated for consecutive reactions, showing an amplification of the effects described above. The results are also presented versus the residence time in the mixer-reactor to show the time window for which the gain is appreciable.

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A rapid diffusion immunoassay in a T-sensor

Cited by 354 publications

References 24 publications

Computerized microfluidic cell culture using elastomeric channels and Braille displays

Computerized microfluidic cell culture using elastomeric channels and Braille displays

Spatially dependent diffusion coefficient as a model for pH sensitive microgel particles in microchannels

Sandwich mixer–reactor: influence of the diffusion coefficient and flow rate ratios

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