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Biomedical subjects

Joel Voldman

Publications and source records attributed to Joel Voldman.

11 recordsLinked to original sources
PubMed2006

High-throughput positive-dielectrophoretic bioparticle microconcentrator.

We introduce a new dielectrophoretic particle microconcentrator that combines interdigitated electrodes with a chaotic mixer to achieve high-throughput (>100 microL/min) particle concentration. The interdigitated electrodes use positive dielectrophoresis to attract particles to the surface, while the chaotic mixer circulates the particles to increase the number brought in proximity with the surface. We have used this microconcentrator to concentrate both beads and B. subtilis spores and have developed a microvolume concentration measurement method to determine the delivered off-chip concentration enhancement of the output sample. The resulting microconcentrator is sufficiently high throughput to serve as an interface between macroscale sample collectors and micro- or nanoscale detectors.

Bacillus subtilis↗
PubMed2006

Engineered systems for the physical manipulation of single cells.

Manipulating the physical location of cells is useful both to organize cells in vitro and to separate cells during screening. The quest to manipulate cells on length scales commensurate with their size has led to a host of technologies exploiting optical, chemical, mechanical, electrical, and other phenomena. Researchers interested in organizing cells are gaining the ability to pattern more than two cell types, to create dynamic surfaces, and to pattern cells in the third dimension. In the realm of cell separation for screening, there has been significant progress in miniaturized flow-based optical sorters as well as in sorting following static microscopic observation.

Animals↗
PubMed2006

Quantitative modeling of dielectrophoretic traps.

We present quantitative modeling software for simulating multiple forces acting on a single particle in a microsystem. In this paper, we focus on dielectrophoretic (DEP) trapping of single cells against fluid flow. The software effectively models the trapping behavior for a range of particles including beads, mammalian cells, viruses, and bacteria. In addition, the software can be used to reveal useful information about the DEP traps - such as multipolar DEP force effects, trap size-selectivity, and effects from varying the flow chamber height. Our modeling software thus serves as a predictive tool, enabling the design of novel DEP traps with superior performance over existing trap geometries. In addition, the software can evaluate a range of trap dimensions to determine the effects on trapping behavior, thus optimizing the trap geometry before it is even fabricated. The software is freely available to the scientific community at: .

Computer Simulation↗
PubMed2006

Microfluidic arrays for logarithmically perfused embryonic stem cell culture.

We present a microfluidic device for culturing adherent cells over a logarithmic range of flow rates. The device sets flow rates through four separate cell-culture chambers using syringe-driven flow and a network of fluidic resistances. The design is easy to fabricate with no on-chip valves and is scalable both in the number of culture chambers as well as in the range of applied flow rates. Using particle velocimetry, we have characterized the flow-rate range. We have also demonstrated an extension of the design that combines the logarithmic flow-rate functionality with a logarithmic concentration gradient across the array. Using fluorescence measurements we have verified that a logarithmic concentration gradient was established in the extended device. Compared with static cell culture, both devices enable greater control over the soluble microenvironment by controlling the transport of molecules to and away from the cells. This approach is particularly relevant for cell types such as embryonic stem cells (ESCs) which are especially sensitive to the microenvironment. We have demonstrated for the first time culture of murine ESCs (mESCs) in continuous, logarithmically scaled perfusion for 4 days, with flow rates varying >300x across the array. Cells grown in the slowest flow rate did not proliferate, while colonies grown in higher flow rates exhibited healthy round morphology. We have also demonstrated logarithmically scaled continuous perfusion culture of 3T3 fibroblasts for 3 days, with proliferation at all flow rates except the slowest rate.

3T3 Cells↗
PubMed2006

Electrical forces for microscale cell manipulation.

Electrical forces for manipulating cells at the microscale include electrophoresis and dielectrophoresis. Electrophoretic forces arise from the interaction of a cell's charge and an electric field, whereas dielectrophoresis arises from a cell's polarizability. Both forces can be used to create microsystems that separate cell mixtures into its component cell types or act as electrical "handles" to transport cells or place them in specific locations. This review explores the use of these two forces for microscale cell manipulation. We first examine the forces and electrodes used to create them, then address potential impacts on cell health, followed by examples of devices for both separating cells and handling them.

Animals↗
PubMed2005

A scalable addressable positive-dielectrophoretic cell-sorting array.

We present the first known implementation of a passive, scalable architecture for trapping, imaging, and sorting individual microparticles, including cells, using a positive dielectrophoretic (p-DEP) trapping array. Our array-based technology enables "active coverslips" where, when scaled, many individually held cells can be sorted based upon imaged spatial or temporally variant characteristics. Our design incorporates a unique "ring-dot" p-DEP trap geometry organized in a row/column array format. This trap design, implemented in a two-level metal process, provides strong and highly spatially localized holding fields enabling single-cell capture for all traps in the array. We release individual trapped microparticles during sorting using a passive transistor-independent approach where we electrically ground the row and column electrodes associated with specific traps in the array. The demand for chip-to-world electrical connections in our arrays scales proportionally with the square root of the number of traps in a given array, delivering a substantial improvement over prior designs. We demonstrate capture, holding, and release operations with both beads and cells in small arrays of this new architecture.

Cell Separation↗
PubMed2004

Dielectrophoretic traps for single-particle patterning.

We present a novel microfabricated dielectrophoretic trap designed to pattern large arrays of single cells. Because flowing away untrapped cells is often the rate-limiting step during cell patterning, we designed the trap to be strong enough to hold particles against practical flow rates. We experimentally validated the trap strength by measuring the maximum flow rate that polystyrene beads could withstand while remaining trapped. These bead experiments have shown excellent agreement with our model predictions, without the use of fitting parameters. The model was able to provide us with a fundamental understanding of how the traps work, and additionally allowed us to establish a set of design rules for optimizing the traps for a wide range of cell sizes. We provide the foundations for an enabling technology that can be used to pattern cells in unique ways, allowing us to do novel cell biology experiments at the microscale.

Cell Culture Techniques↗
PubMed2004

Dielectrophoretic registration of living cells to a microelectrode array.

We present a novel microfabricated device to simultaneously and actively trap thousands of single mammalian cells in alignment with a planar microelectrode array. Thousands of 3 Ipm diameter trapping electrodes were fabricated within the bottom of a parallel-plate flow chamber. Cells were trapped on the electrodes and held against destabilizing fluid flows by dielectrophoretic forces generated in the device. In general, each electrode trapped only one cell. Adhesive regions were patterned onto the surface in alignment with the traps such that cells adhered to the array surface and remained in alignment with the electrodes. By driving the device with different voltages, we showed that trapped cells could be killed by stronger electric fields. However, with weaker fields, cells were not damaged during trapping, as indicated by the similar morphologies and proliferation rates of trapped cells versus controls. As a test of the device, we patterned approximately 20,000 cells onto aI cm2 grid of rectangular adhesive regions, with two electrodes and thus two cells per rectangle. Our method obtained 70 +/- 1% fidelity versus 17 +/- 1% when using an existing cell-registration technique. By allowing the placement of desired numbers of cells at specified locations, this approach addresses many needs to manipulate and register cells to the surfaces of biosensors and other devices with high precision and fidelity.

Animals↗
PubMed2004

Dielectrophoretic registration of living cells to a microelectrode array.

We present a novel microfabricated device to simultaneously and actively trap thousands of single mammalian cells in alignment with a planar microelectrode array. Thousands of 3 micromdiameter trapping electrodes were fabricated within the bottom of a parallel-plate flow chamber. Cells were trapped on the electrodes and held against destabilizing fluid flows by dielectrophoretic forces generated in the device. In general, each electrode trapped only one cell. Adhesive regions were patterned onto the surface in alignment with the traps such that cells adhered to the array surface and remained in alignment with the electrodes. By driving the device with different voltages, we showed that trapped cells could be killed by stronger electric fields. However, with weaker fields, cells were not damaged during trapping, as indicated by the similar morphologies and proliferation rates of trapped cells versus controls. As a test of the device, we patterned approximately 20000 cells onto a 1cm(2) grid of rectangular adhesive regions, with two electrodes and thus two cells per rectangle. Our method obtained 70+/-1% fidelity versus 17+/-1% when using an existing cell-registration technique. By allowing the placement of desired numbers of cells at specified locations, this approach addresses many needs to manipulate and register cells to the surfaces of biosensors and other devices with high precision and fidelity.

Animals↗
PubMed2002

A microfabrication-based dynamic array cytometer.

We have developed a microfabricated device for use in parallel luminescent single-cell assays that can sort populations upon the basis of dynamic functional responses to stimuli. This device is composed of a regular array of noncontact single-cell traps. These traps use dielectrophoresis to stably confine cells and hold them against disrupting fluid flows. Using quantitative modeling, we have designed traps with a novel asymmetric extruded-quadrupole geometry. This new trap can be physically arrayed and electrically addressed, enabling our cytometer. Situating an array of these traps in a microchannel, we have introduced cells into the array and demonstrated observation of fluorescent dynamic responses followed by sorting. Such a device has potential for use in investigating functional processes, as revealed by temporal behavior, in large numbers of single cells.

Cell Separation↗