Abstract: Nanofluidic entropic traps, comprising alternating thin and thick regions, sieve small molecules such as DNA or protein polymers and other molecules. The thick region is comparable or substantially larger than the molecule to be separated, while the thin region is substantially smaller than the size of the molecules to be separated. Due to the molecular size dependence of the entropic trapping effect, separation of molecules may be achieved. In addition, entropic traps are used to collect, trap and control many molecules in the nanofluidic channel. A fabrication method is disclosed to provide an efficient way to make nanofluidic constrictions in any fluidic devices.

Abstract: A three dimensional microfluidic device is formed by placing a membrane between two micropatterned chips. The membrane is positioned to cover the area where channels intersect. In one embodiment the membrane is porous. The chips are formed of plastic, and are thermally bonded under pressure. Reservoirs are formed on the chips at each end of each channel. The channels are created in the chip by use of an embossing master, such as a patterned silicon wafer. The reservoirs are formed by drilling. A hydraulic press is used to emboss both chips, and is also used to thermally bond the chips and membrane under pressure. The surfaces of the channels are oxidized, changing the surfaces from hydrophobic to hydrophilic.

Abstract: The present invention is directed to a method and an apparatus for analysis of an analyte. The method involves providing a zero-mode waveguide which includes a cladding surrounding a core where the cladding is configured to preclude propagation of electromagnetic energy of a frequency less than a cutoff frequency longitudinally through the core of the zero-mode waveguide. The analyte is positioned in the core of the zero-mode waveguide and is then subjected, in the core of the zero-mode waveguide, to activating electromagnetic radiation of a frequency less than the cut-off frequency under conditions effective to permit analysis of the analyte in an effective observation volume which is more compact than if the analysis were carried out in the absence of the zero-mode waveguide.

Abstract: A micro-electrical mechanical oscillator has a resonant frequency of oscillation that is varied by application of heat. The resonant frequency is varied at a frequency different from the resonant frequency of the oscillator to amplify oscillations. In one embodiment, the oscillator is disc of material supported by a pillar of much smaller diameter than the disc. The periphery of the disc is heated by a laser to provide a time varying shift of the resonant frequency (or equivalently the stiffness) of the disc. Feedback from movement of the disc is used to modulate the intensity of the laser, and thus the stiffness of the disc to provide parametric amplification of sensed vibrations, using heating as a pump. Various other shapes of micro-electrical mechanical oscillators are used in other embodiment, including an array of such oscillators on a substrate, each having different resonant frequencies.

Abstract: Biomolecular photo-based patterning methods utilize avidin-biotin technology to immobilize functional proteins on the inner surface of silica glass tubes in desired patterns. The methods are useful for nanofluidic affinity biosensor/chromatography systems and on silicon dioxide substrates for biosensor applications. The resulting patterns are optimized based on the application. A zebra shaped pattern is utilized for an affinity chromatography system.

Abstract: A microfluidic device has features that reduce the speed of flow of higher speed diffusing molecules. The features are used to separate various components of a mixture in the microfluidic device. The channel is sized to ensure laminar flow of the mixture to promote only diffusive mixing of the components. Wells extend from the channel. Components having higher diffusing velocities are slowed by the wells as the mixture proceeds through the channel. The result is that slower speed diffusing components exit the channel prior to the lower speed diffusing components. The device is formed by use of photolithographic techniques or other techniques capable of forming such features.

Abstract: A method of patterning a preselected material on a substrate is provided, comprising coating a substrate surface with a releasable polymer coating, creating one or more openings through the polymer coating to expose a portion of the substrate surface in a predefined pattern, coating at least a portion of the substrate surface that is exposed through the polymer coating with at least one preselected material, and optionally, removing said polymer coating so that the material is retained on said substrate surface in said predefined pattern.

Abstract: The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site.

Abstract: Electron beam lithography is used to make very small mechanical structures in single-crystal silicon. The structure may be a mesh having beam widths of less than 30 nm and suspended in a wafer, above a substrate. An rf drive voltage applied between the suspended structure and the underlying substrate produces vibration at or near the resonant frequency of the structure, and optical interference techniques are used to detect and measure the motion of the structure. The small dimensions of the structure provides a resonant frequency above 40 MHz. In one embodiment, the structure is a mesh formed of interconnected, very narrow, high aspect ratio parallel beams spaced about 315 nm apart. This results in a nanostructure having a low mass and a large relative surface area.

Abstract: A polycarbonate polymer such as poly(cyclohexene carbonate) acts as a positive electron beam resist, is substantially transparent to ultra violet light and that depolymerizes when heated. The polymer acts as a positive electron beam resist at 5 kV, and depolymerizes at temperatures between approximately 200-300° C. The polymer is removable from underneath other layers by heating, facilitating fabrication of overhanging structures such as tubes by depositing layers on top of the polymer.

Abstract: Separation of long molecules by length is obtained by forcing such molecules to traverse a boundary between a low free-energy region and a high free-energy region. In one embodiment, the high free-energy region is a dense pillar region or other structure formed on a semiconductor substrate. One or more membranes are used in further embodiments. The low free-energy region is a larger chamber formed adjacent the high free-energy region. A recoil phase allows longer molecules not fully driven into the high free-energy region to recoil into the low free-energy region. In a further variation, the high free-energy region is a membrane having nanoscale holes.

Abstract: Fabrication techniques for forming arbitrarily shaped fluid capillaries at dimensions below 1 &mgr;m and for forming optical waveguides in the same devices with the same fabrication processes include methods to make integral optical waveguide/fluid-flow systems for greater miniaturization, integration and parallelism of optical excitation and detection systems for the sampling of small volumes. Capillaries with widths below 1 &mgr;m dimensions are fabricated using photolithography and reactive ion etching on glass substrates or by provision of a sacrificial layer, having the configuration desired for a microchannel, covered by a high refractive index material in which a waveguide is formed. Removal of the sacrificial layer produces a microchannel aligned with the waveguide. Dye labeled DNA molecules are driven electrophoretically through the micrometer size channels light emission from and individual molecules can be observed.

Abstract: A resonator device utilizes two small mechanical resonators that are electrostatically coupled. A first resonator receives an input signal near its resonant frequency, and the input signal and a second signal are summed and provided to a second resonator. The resonant frequency of the second resonator is approximately equal to the second signal frequency. A width of response of the amplifier is tuned by varying the pump voltage. Resonant frequencies of corresponding individual oscillators are tuned by adjusting bias voltages.

Abstract: The present invention provides a method of patterning a self-assembled monolayer (SAM) on a substrate comprising employing low electron-beam lithography to selectively deactivate functional groups at the surface of said SAM in a preselected area of said surface, wherein said functional groups bind to a target substance but said deactivated functional groups do not, so that the surface of said SAM can be contacted with said target substance so that the target substance binds to said functional groups but does not bind to said deactivated groups in said preselected area, to yield a pattern of said target substance on said surface.

Abstract: A new technique for fabricating two-dimensional and three-dimensional fluid microchannels for molecular studies includes fabricating a monolithic unit using planar processing techniques adapted from semiconductor electronics fabrication. A fluid gap between a floor layer (12) and a ceiling layer (20) is provided by an intermediate patterned sacrificial layer (14) which is removed by a wet chemical etch. The process may be used to produce a structure such as a filter or artificial gel by using Electron beam lithography to define a square array of 100 nm holes (30) in the sacrificial layer. CVD silicon nitride (54) is applied over the sacrificial layer and enters the array of holes to produce closely spaced pillars. The sacrificial layer can be removed with a wet chemical etch through access holes in the ceiling layer, after which the access holes are sealed with VLTO silicon dioxide (64).

Abstract: An optical biological detector is able to bind specific targeted bacterial cells by stamping an antibody grating pattern onto a silicon surface. The antibody grating alone produces insignificant optical diffraction, but upon immunocapture of the targeted cells, the optical phase change produces a diffraction pattern. Micro-contact printing provides a method for placing the antibody grating pattern directly onto a substrate surface with no additional processes or binding chemicals. Antibodies or other biologically active material may be stamped directly onto clean native oxide silicon substrates with no other chemical surface treatments. Direct binding of the antibodies to the silicon occurs in a way that still allows them to function and selectively bind antigen. The performance of the sensor was evaluated by capturing Escherichia coli O157:H7 cells on the antibody-stamped lines and measuring the intensity of the first order diffraction beam resulting from the attachment of cells.

Abstract: Apparatus for optical analysis of a sample material includes a channel block incorporating microfabricated channels and an integral gel material. Illuminating optics direct light to the sample material and light reflected from, refracted by and/or emitted by the sample is collected by collection optics for detection. The gel material is formed within the channels and includes multiple closely spaced pillars to form a porous separator for sample material to be analyzed.

Abstract: Apparatus for optical analysis of a sample material includes a channel block incorporating microfabricated channels and an integral gel material. Illuminating optics direct light to the sample material and light reflected from, refracted by and/or emitted by the sample is collected by collection optics for detection. The gel material is formed within the channels and includes multiple closely spaced pillars to form a porous separator for sample material to be analyzed.

Abstract: A process employing bodies that are fabricated to have a specific configuration are useful for the storage of information such as digital data. In one embodiment a material, such as germanium, is etched to produce a structure having a multiplicity of columnar or conical features. By providing a sufficient number of these features per unit area, it is possible to store at a relatively high density a variety of information. This information storage is accomplished by melting the columns or cones in a localized area. If these structures are of the appropriate size and spacing, they appear optically absorbing before melting and a reflective region appears in the treated area. In this manner archival storage of densely packed information is possible.

Abstract: A display cell having at least two states of different opacity, comprises a first material having a first index of refraction, a second material dispersed within the first material and having a second index of refraction, the difference between the first and the second indices of refraction being variable over a range of values, and means for varying the difference in index of refraction over a portion of the range. When the indices of refraction of the first and second material are substantially the same, the display is substantially transparent. Otherwise it is opaque or substantially less transparent.