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Biomedical subjects

Alex Groisman

Publications and source records attributed to Alex Groisman.

8 recordsLinked to original sources

High-throughput and high-resolution flow cytometry in molded microfluidic devices.

We describe the design, fabrication, and operation of two types of flow cytometers based on microfluidic devices made of a single cast of poly(dimethylsiloxane). The stream of particles or cells injected into the devices is hydrodynamically focused in both transverse and lateral directions, has a uniform velocity, and has adjustable diameter and shape. The cytometry system built around the first microfluidic device has fluorescence detection accuracy comparable with that of a commercial flow cytometer and can analyze as many as 17 000 particles/s. This high-throughput microfluidic device could be used in inexpensive stand-alone cytometers or as a part of integrated microanalysis systems. In the second device, a stream of particles is focused to a flow layer of a submicrometer thickness that allows imaging the particles with a high numerical aperture microscope objective. To take long-exposure, low-light fluorescence images of live cells, the device is placed on a moving stage, which accurately balances the translational motion of particles in the flow. The achieved resolution is comparable to that of still micrographs. This high-resolution device could be used for analysis of morphology and fluorescence distribution in cells in continuous flow.

Flow Cytometry↗

Separation of plasma from whole human blood in a continuous cross-flow in a molded microfluidic device.

We designed, fabricated, and tested a microfluidic device for separation of plasma from whole human blood by size exclusion in a cross-flow. The device is made of a single mold of a silicone elastomer poly(dimethylsiloxane) (PDMS) sealed with a cover glass and is essentially disposable. When loaded with blood diluted to 20% hematocrit and driven with pulsatile pressure to prevent clogging of the channels with blood cells, the device can operate for at least 1 h, extracting approximately 8% of blood volume as plasma at an average rate of 0.65 microL/min. The flow in the device causes very little hemolysis; the extracted plasma meets the standards for common assays and is delivered to the device outlet approximately 30 s after injection of blood to the inlet. Integration of the cross-flow microchannel array with on-chip assay elements would create a microanalysis system for point-of-care diagnostics, reducing costs, turn-around times, and volumes of blood sample and reagents required for the assays.

Female↗

Chaotic mixing in a steady flow in a microchannel.

We report experiments on mixing of a passively advected fluorescent dye in a low Reynolds number flow in a microscopic channel. The channel is a chain of repeating segments with a custom designed profile that generates a steady three-dimensional flow with stretching and folding, and chaotic mixing. A few statistical characteristics of mixing in the flow are studied and are all found to agree with theoretical and experimental results for the flows in the Batchelor regime of mixing that are chaotic in time. The proposed microchannel provides fast and efficient mixing and is simple to fabricate.

Journal Article↗

A microfluidic chemostat for experiments with bacterial and yeast cells.

Bacteria and yeast frequently exist as populations capable of reaching extremely high cell densities. With conventional culturing techniques, however, cell proliferation and ultimate density are limited by depletion of nutrients and accumulation of metabolites in the medium. Here we describe design and operation of microfabricated elastomer chips, in which chemostatic conditions are maintained for bacterial and yeast colonies growing in an array of shallow microscopic chambers. Walls of the chambers are impassable for the cells, but allow diffusion of chemicals. Thus, the chemical contents of the chambers are maintained virtually identical to those of the nearby channels with continuous flowthrough of a dynamically defined medium. We demonstrate growth of cell cultures to densely packed ensembles that proceeds exponentially in a temperature-dependent fashion, and we use the devices to monitor colony growth from a single cell and to analyze the cell response to an exogenously added autoinducer.

Bioreactors↗

Chaotic flow and efficient mixing in a microchannel with a polymer solution.

Microscopic flows are almost universally linear, laminar, and stationary because the Reynolds number, Re, is usually very small. That impedes mixing in microfluidic devices, which sometimes limits their performance. Here, we show that truly chaotic flow can be generated in a smooth microchannel of a uniform width at arbitrarily low Re, if a small amount of flexible polymers is added to the working liquid. The chaotic flow regime is characterized by randomly fluctuating three-dimensional velocity field and significant growth of the flow resistance. Although the size of the polymer molecules extended in the flow may become comparable to the microchannel width, the flow behavior is fully compatible with that in a macroscopic channel in the regime of elastic turbulence. The chaotic flow leads to quite efficient mixing, which is almost diffusion independent. For macromolecules, mixing time in this microscopic flow can be three to four orders of magnitude shorter than due to molecular diffusion.

Journal Article↗

A microfluidic rectifier: anisotropic flow resistance at low Reynolds numbers.

It is one of the basic concepts of Newtonian fluid dynamics that at low Reynolds number (Re) the Navier-Stokes equation is linear and flows are reversible. In microfluidic devices, where Re is essentially always low, this implies that flow resistance in microchannels is isotropic. Here we present a microfluidic rectifier: a microscopic channel of a special shape whose flow resistance is strongly anisotropic, differing by up to a factor of 2 for opposite flow directions. Its nonlinear operation at arbitrary small Re is due to non-Newtonian elastic properties of the working fluid, which is a 0.01% aqueous solution of a high molecular weight polymer. The rectifier works as a dynamic valve and may find applications in microfluidic pumps and other integrated devices.

Journal Article↗

Microfluidic memory and control devices.

We demonstrate microscopic fluidic control and memory elements through the use of an aqueous viscoelastic polymer solution as a working fluid. By exploiting the fluid's non-Newtonian rheological properties, we were able to demonstrate both a flux stabilizer and a bistable flip-flop memory. These circuit elements are analogous to their solid-state electronic counterparts and could be used as components of control systems for integrated microfluidic devices. Such miniaturized fluidic circuits are insensitive to electromagnetic interference and may also find medical applications for implanted drug-delivery devices.

Journal Article↗