Abstract: A method of producing nanoscale features on a pre-stressed polymer film is described herein. The method includes: imprinting the pre-stressed polymer film with a nanoscale or microscale pattern; constraining the pre-stressed polymer film in a first direction with a first constraint; shrinking the pre-stressed polymer film in a second direction with a first heat treatment process; releasing the first uniaxial constraint; constraining the pre-stressed polymer film in a third direction with a second constraint, the third direction being different than the first direction; shrinking the pre-stressed polymer film in a fourth direction with a second heat treatment process; and releasing the second constraint to produce the nanoscale features on the pre-stressed polymer film.

Abstract: This application discloses a method for preparing a construct comprising preparing a mixture of an extracellular matrix and a plurality of cells suspended in a first cell culture medium, applying a crosslinking or gelation agent to the mixture, depositing the mixture into a mold of a defined shape, allowing the extracellular matrix in the mixture to crosslink or gel for a duration of about 1 hour to about 4 hours, applying a second cell culture medium to the mixture containing crosslinked or gelled extracellular matrix, and allowing cell directed self-assembly of the mixture for a duration of about 2 hours to about 10 hours to form a construct, wherein the construct is a three-dimensional structure formed within the mold of the defined shape. Optionally, the method further comprises applying at least one stimuli to the mixture or the construct. Also provided are constructs prepared according to the methods disclosed herein.

Abstract: This application provides constructs for use as complex cell systems of a desired shape and methods of preparing thereof. The constructs comprise cells contained within a biocompatible gel matrix deposited on a scaffold material optionally cut into defined patterns and impregnated with a crosslinking agent, wherein the biocompatible gel matrix crosslinks upon contact with the crosslinking agent on the scaffold. By stacking multiple alternating layers of the scaffold material cut into defined patterns and the biocompatible gel matrix deposited on the scaffold in defined patterns, complex 3D structures with features like embedded channels are be formed. These complex cell system constructs can be used as in vitro models of biological processes.

Abstract: A device and associated method to concentrate cells such as bacteria/viruses, lyse them, and extract biomolecules such as DNA is described. A nanoporous membrane is sandwiched between two microfluidic channels to create thousands of parallel nanopore traps for bacteria or viruses. The application of an electric potential across the membrane results in the electrophoretic accumulation of cells at the nanoporous membrane. The application of moderate voltages is able to produce a high local electric field for lysis of the cells or the disintegration of the virus particles resulting in the extraction of biomolecules such as DNA.

Abstract: A method for the detection of metabolically active cells using microwells is provided. A sample containing one or more cells is segmented into a plurality of microwells each containing a metabolic indicator. The microwells are then monitored for a change in the level or activity of a metabolic indicator, thereby indicating the presence or absence of metabolically active cells in each microwell. Also provided are methods for the detection of cells such as bacteria that are resistant to antibiotics or for the detection of particular cell types such as mycobacteria. Also provided are screening methods for identifying compounds with an effect on cell growth or metabolism.

Abstract: A method of controlling nematode response in a microfluidic environment is provided comprising exposing the nematode to an electric field that induces a nematode response. In one embodiment, a method of sorting a group of nematodes based on a selected parameter is provided comprising the step of exposing the nematodes to an electric field that induces a differential response among the nematodes based on the selected parameter, wherein the differential response functions to separate the nematodes based on the selected parameter. Devices useful to achieve these methods are also provided.

Abstract: A method of controlling nematode response in a microfluidic environment is provided comprising exposing the nematode to an electric field that induces a nematode response. In one embodiment, a method of sorting a group of nematodes based on a selected parameter is provided comprising the step of exposing the nematodes to an electric field that induces a differential response among the nematodes based on the selected parameter, wherein the differential response functions to separate the nematodes based on the selected parameter. Devices useful to achieve these methods are also provided.

Abstract: A substance delivery apparatus is disclosed. Embodiments of the substance delivery apparatus comprise a housing defining a reservoir containing the substance. At least one micro-needle is operably connected to the reservoir. A micro-pump is fluidically connected to the reservoir so that when the micro-pump is activated, the substance is directed from the reservoir, through the at least one micro-needle.

Abstract: A micro-discharge optical source apparatus and a method and system which utilizes the apparatus to analyze a sample are provided. The apparatus includes a substrate and an anode electrode and a cathode electrode supported on the substrate. One of the electrodes, such as the cathode, is preferably a liquid electrode. The electrodes are spaced apart to define an inter-electrode gap therebetween. The apparatus further includes a voltage source for applying a voltage between the electrodes sufficient to generate a glow micro-discharge in the gap to cause a first emission having a first desired excitation spectrum. An optical element is integrated with the substrate to direct the first emission to travel along an optical path including an axis. In one embodiment, the system detects the direct fluorescence of a sample such as tryptophan and other amino acids. In another embodiment, the system detects fluorescence of dye-labeled biochemicals.

Abstract: The present invention relates to microfabrication and utilization of microscale electrophoresis devices as well as the separation and detection of biomolecules in microscale electrophoresis devices. The device of the present invention utilizes novel fabrication and detection methods.

Abstract: A micromachined probe apparatus and methods for making and using same to characterize liquid in a fluidic channel and map embedded charge in a sample on a substrate are provided. The probe apparatus includes an integrated scanning tip and a dither actuation mechanism. The actuation is achieved using a bent-beam electrothermal actuator, and the probe tip is insulated from the actuator with a wide isolation gap. The device is fabricated by a modified micro electro-discharge machining process which allows electrical isolation within the micromachined structure using an epoxy plug. The apparatus may be used to measure changes in the external surface potential of a microfluidic channel as a function of varying pH of liquid inside the channel. The apparatus also may be used to map embedded charge in a thin layer on a substrate, showing it to be suitable for monitoring microelectronics manufacturing processes.

Abstract: A micro-discharge optical source apparatus and a method and system which utilizes the apparatus to analyze a sample are provided. The apparatus includes a substrate and an anode electrode and a cathode electrode supported on the substrate. One of the electrodes, such as the cathode, is preferably a liquid electrode. The electrodes are spaced apart to define an inter-electrode gap therebetween. The apparatus further includes a voltage source for applying a voltage between the electrodes sufficient to generate a glow micro-discharge in the gap to cause a first emission having a first desired excitation spectrum. An optical element is integrated with the substrate to direct the first emission to travel along an optical path including an axis. In one embodiment, the system detects the direct fluorescence of a sample such as tryptophan and other amino acids. In another embodiment, the system detects fluorescence of dye-labeled biochemicals.

Abstract: A micromachined probe apparatus and methods for making and using same to characterize liquid in a fluidic channel and map embedded charge in a sample on a substrate are provided. The probe apparatus includes an integrated scanning tip and a dither actuation mechanism. The actuation is achieved using a bent-beam electrothermal actuator, and the probe tip is insulated from the actuator with a wide isolation gap. The device is fabricated by a modified micro electro-discharge machining process which allows electrical isolation within the micromachined structure using an epoxy plug. The apparatus may be used to measure changes in the external surface potential of a microfluidic channel as a function of varying pH of liquid inside the channel. The apparatus also may be used to map embedded charge in a thin layer on a substrate, showing it to be suitable for monitoring microelectronics manufacturing processes.

Abstract: A composition, method and use is disclosed for a porous plug that functions as an electro-osmotic pump. The polymer eliminates any back pressure effects while enhancing the electro-osmotic flow in a channel. The pump is bach fabricated by surface micromachining on top of a silicon wafer. The pump device is driven by an alternating zero-average injected current signal at low frequencies producing a bubble-free electro-osmotic flow with a reversible net movement. The device is capable of an average water-air interface velocity of 1.8 &mgr;m/second at 0.8 Hz. The velocity may be increased from between 4.8-13.9 &mgr;m/second by necking down the channel size.

Abstract: The present invention relates to microfabrication and utilization of microscale electrophoresis devices as well as the separation and detection of biomolecules in microscale electrophoresis devices. The device of the present invention utilizes novel fabrication and detection methods.