Abstract: A source signal is converted into a time-variant temperature field with transduction into mechanical motion. In one embodiment, the conversion of a source signal into the time-variant temperature field is provided by utilizing a micro-fabricated fast response, bolometer-type radio frequency power meter. A resonant-type micromechanical thermal actuator may be utilized for temperature read-out and demodulation.

Abstract: An array of micromechanical oscillators have different resonant frequencies based on their geometries. In one embodiment, a micromechanical oscillator has a resonant frequency defined by an effective spring constant that is modified by application of heat. 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 to modify the resonant frequency (or equivalently the spring constant or stiffness) of the disc. Continuous control of the output phase and frequency may be achieved when the oscillator becomes synchronized with an imposed sinusoidal force of close frequency. The oscillator frequency can be detuned to produce an easily controlled phase differential between the injected signal and the oscillator feedback. A phased array radar may be produced using independent phase controllable oscillators.

Abstract: An optical apparatus that provides extraordinary light transmission through a sub-wavelength-sized light transmitting region of the apparatus includes a core region of dielectric material having a complex dielectric constant, ?1, surrounded by a metallic cladding material having a complex dielectric constant, ?2, wherein the core region has a maximum dimension, 2a, further wherein 2a is less than ?, where ? is the free-space wavelength of light incident on an input side of the apparatus, and further wherein |?1| is greater than 0.5|?2|, ?1 has a positive real part, and ?2 has a negative real part, whereby the incident light will be transmitted by and exit the apparatus from an output side with extraordinary transmission.

Abstract: A method for manufacturing or preparing thin-film stacks that exhibit moderate, finite, stress-dependent resistance and which can be incorporated into a transduction mechanism that enables simple, effective signal to be read out from a micro- or nano-mechanical structure. As the structure is driven, the resistance of the intermediate layers is modulated in tandem with the motion, and with suitable dc-bias, the motion is directly converted into detectable voltage. In general, detecting signal from MEMS or NEMS devices is difficult, especially using a method that is able to be integrated with standard electronics. The thin-film manufacturing or preparation technique described herein is therefore a technical advance in the field of MEMS/NEMS that could enable new applications as well as the ability to easily develop CMOS-MEMS integrated fabrication techniques.

Abstract: An active micromixer uses a surface acoustic wave, preferably a Rayleigh wave, propagating on a piezoelectric substrate to induce acoustic streaming in a fluid in a microfluidic channel. The surface acoustic wave can be generated by applying an RF excitation signal to at least one interdigital transducer on the piezoelectric substrate. The active micromixer can rapidly mix quiescent fluids or laminar streams in low Reynolds number flows. The active micromixer has no moving parts (other than the SAW transducer) and is, therefore, more reliable, less damaging to sensitive fluids, and less susceptible to fouling and channel clogging than other types of active and passive micromixers. The active micromixer is adaptable to a wide range of geometries, can be easily fabricated, and can be integrated in a microfluidic system, reducing dead volume. Finally, the active micromixer has on-demand on/off mixing capability and can be operated at low power.

Abstract: The present invention is directed to a method of sequencing a target nucleic acid. The method provides a complex comprising a polymerase enzyme, a target nucleic acid molecule, and a primer, wherein the complex is immobilized on a support Fluorescent label is attached to a terminal phosphate group of the nucleotide or nucleotide analog. The growing nucleic acid strand is extended by using the polymerase to add a nucleotide analog to the nucleic acid strand. The nucleotide analog added to the oligonucleotide primer as a result of the polymerizing step is identified. The time duration of the signal from labeled nucleotides or nucleotide analogs that become incorporated is distinguished from freely diffusing labels by a longer retention in the observation volume for the nucleotides or nucleotide analogs that become incorporated than for the freely diffusing labels.

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. Each type of labeled nucleotide comprises an acceptor fluorophore attached to a phosphate portion of the nucleotide such that the fluorophore is removed upon incorporation into a growing strand. Fluorescent signal is emitted via fluorescent resonance energy transfer between the donor fluorophore and the acceptor fluorophore as each nucleotide is incorporated into the growing strand. The sequence is deduced by identifying which base is being incorporated into the growing strand.

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: A system and method for detecting mass based on a frequency differential of a resonating micromachined structure, such as a cantilever beam. A high aspect ratio cantilever beam is coated with an immobilized binding partner that couples to a predetermined cell or molecule. A first resonant frequency is determined for the cantilever having the immobilized binding partner. Upon exposure of the cantilever to a solution that binds with the binding partner, the mass of the cantilever beam increases. A second resonant frequency is determined and the differential resonant frequency provides the basis for detecting the target cell or molecule. The cantilever may be driven externally or by ambient noise. The frequency response of the beam can be determined optically using reflected light and two photodetectors or by interference using a single photodetector.

Abstract: The present invention is directed to a CMOS integrated micromechanical device fabricated in accordance with a standard CMOS foundry fabrication process. The standard CMOS foundry fabrication process is characterized by a predetermined layer map and a predetermined set of fabrication rules. The device includes a semiconductor substrate formed or provided in accordance with the predetermined layer map and the predetermined set of fabrication rules. A MEMS resonator device is fabricated in accordance with the predetermined layer map and the predetermined set of fabrication rules. The MEMS resonator device includes a micromechanical resonator structure having a surface area greater than or equal to approximately 20 square microns. At least one CMOS circuit is coupled to the MEMS resonator member. The at least one CMOS circuit is also fabricated in accordance with the predetermined layer map and the predetermined set of fabrication rules.

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: An array of micromechanical oscillators have different resonant frequencies based on their geometries. In one embodiment, a micromechanical oscillator has a resonant frequency defined by an effective spring constant that is modified by application of heat. 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 to modify the resonant frequency (or equivalently the spring constant or stiffness) of the disc. Continuous control of the output phase and frequency may be achieved when the oscillator becomes synchronized with an imposed sinusoidal force of close frequency. The oscillator frequency can be detuned to produce an easily controlled phase differential between the injected signal and the oscillator feedback. A phased array radar may be produced using independent phase controllable oscillators.

Abstract: A system and method for detecting mass based on a frequency differential of a resonating micromachined structure, such as a cantilever beam. A high aspect ratio cantilever beam is coated with an immobilized binding partner that couples to a predetermined cell or molecule. A first resonant frequency is determined for the cantilever having the immobilized binding partner. Upon exposure of the cantilever to a solution that binds with the binding partner, the mass of the cantilever beam increases. A second resonant frequency is determined and the differential resonant frequency provides the basis for detecting the target cell or molecule. The cantilever may be driven externally or by ambient noise. The frequency response of the beam can be determined optically using reflected light and two photodetectors or by interference using a single photodetector.

Abstract: The present invention relates to compositions, methods, and uses for obtaining sequence information from nucleic acid molecules.

Abstract: An array of micromechanical oscillators have different resonant frequencies based on their geometries. In one embodiment, a micromechanical oscillator has a resonant frequency defined by an effective spring constant that is modified by application of heat. 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 to modify the resonant frequency (or equivalently the spring constant or stiffness) of the disc. Continuous control of the output phase and frequency may be achieved when the oscillator becomes synchronized with an imposed sinusoidal force of close frequency. The oscillator frequency can be detuned to produce an easily controlled phase differential between the injected signal and the oscillator feedback. A phased array radar may be produced using independent phase controllable oscillators.

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: A micromechanical resonator is formed on a substrate. The resonator has a partial spherical shell clamped on an outside portion of the shell to the substrate. In other embodiments, a flat disc or other shape may be used. Movement is induced in a selected portion of the disc, inducing easily detectible out-of-plane motion. A laser is used in one embodiment to heat the selected portion of the disc and induce the motion. The motion may be detected by capacitive or interferometric techniques.

Abstract: An array is formed with a protective cover on a substrate. The protective cover is patterned to produce an array of openings to the substrate. Desired material is deposited on the substrate through the openings. The protective cover may then be removed. In one embodiment, the protective cover is a conformal polymer, such as di-para-xylylene. It may be removed by mechanical peeling. The material may be biological material such as DNA. The protective cover may be used to prevent non-specific hybridization in inter-spot regions by performing hybridization with the cover still in place. Hybridization that occurs in such regions between the spots may be removed with removal of the protective cover.

Abstract: A nanofluidic channel fabricated in fused silica with an approximately 500 nm square cross section was used to isolate, detect and identify individual quantum dot conjugates. The channel enables the rapid detection of every fluorescent entity in solution. A laser of selected wavelength was used to excite multiple species of quantum dots and organic molecules, and the emission spectra were resolved without significant signal rejection. Quantum dots were then conjugated with organic molecules and detected to demonstrate efficient multicolor detection. PCH was used to analyze coincident detection and to characterize the degree of binding. The use of a small fluidic channel to detect quantum dots as fluorescent labels was shown to be an efficient technique for multiplexed single molecule studies. Detection of single molecule binding events has a variety of applications including high throughput immunoassays.

Abstract: A nanofluidic channel fabricated in fused silica with an approximately 500 nm square cross section was used to isolate, detect and identify individual quantum dot conjugates. The channel enables the rapid detection of every fluorescent entity in solution. A laser of selected wavelength was used to excite multiple species of quantum dots and organic molecules, and the emission spectra were resolved without significant signal rejection. Quantum dots were then conjugated with organic molecules and detected to demonstrate efficient multicolor detection. PCH was used to analyze coincident detection and to characterize the degree of binding. The use of a small fluidic channel to detect quantum dots as fluorescent labels was shown to be an efficient technique for multiplexed single molecule studies. Detection of single molecule binding events has a variety of applications including high throughput immunoassays.