Abstract: A system, device and method for electroporation of living cells and the introduction of selected molecules into the cells utilizes a fluidic system where living cells and biologically active molecules flow through a channel that exposes them to electric fields, causing the molecules to be transferred across the cell membrane. The device is structured in a manner that allows precise control of the cells location, motion, and exposure to electric fields within the flow channel device. The method is particularly well suited for the introduction of DNA, RNA, drug compounds, and other biologically active molecules into living cells.

Abstract: The present invention relates to a device for isolating and recovering a biomolecule from a test sample. The device includes a support and at least one peelable layer deposited on at least a portion of the support. The peelable layer includes a substrate having a target component immobilized on the substrate. The device is effective for isolating and recovering a biomolecule having affinity to the target component. The present invention also relates to systems and methods of using the device. The present invention also relates to a biomolecule elution strip and related methods.

Abstract: The first aspect of the present invention is directed to a method of producing a vascular network preform (VNP). This method involves forming a network of elongate fibers and at least one elongate structure from a sacrificial material. The diameter of the elongate structure is greater than that of the elongate fibers. The network of elongate fibers is placed in contact with at least one elongate structure either following or during forming the network of elongate fibers or forming the at least one elongate structure. A matrix is applied around the network of elongate fibers, in contact with the at least one elongate structure. The network of elongate fibers and elongate structure, within the matrix is sacrificed to form a preform. The resulting preform contains a vascular network of fine diameter tubes in contact with at least one elongate passage having a diameter greater than that of the fine diameter tubes. The resulting solid preform and methods of using it are also disclosed.

Abstract: The present invention relates to a device for isolating and recovering a biomolecule from a test sample. The device includes a support and at least one peelable layer deposited on at least a portion of the support. The peelable layer includes a substrate having a target component immobilized on the substrate. The device is effective for isolating and recovering a biomolecule having affinity to the target component. The present invention also relates to systems and methods of using the device. The present invention also relates to a biomolecule elution strip and related methods.

Abstract: The present invention relates to a device for isolating and recovering a biomolecule from a test sample. The device includes a support and at least one peelable layer deposited on at least a portion of the support. The peelable layer includes a substrate having a target component immobilized on the substrate. The device is effective for isolating and recovering a biomolecule having affinity to the target component. The present invention also relates to systems and methods of using the device. The present invention also relates to a biomolecule elution strip and related methods.

Abstract: The first aspect of the present invention is directed to a method of producing a vascular network preform (VNP). This method involves forming a network of elongate fibers and at least one elongate structure from a sacrificial material. The diameter of the elongate structure is greater than that of the elongate fibers. The network of elongate fibers is placed in contact with at least one elongate structure either following or during forming the network of elongate fibers or forming the at least one elongate structure. A matrix is applied around the network of elongate fibers, in contact with the at least one elongate structure. The network of elongate fibers and elongate structure, within the matrix is sacrificed to form a preform. The resulting preform contains a vascular network of fine diameter tubes in contact with at least one elongate passage having a diameter greater than that of the fine diameter tubes. The resulting solid preform and methods of using it are also disclosed.

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: 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: 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 wave guide, 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 method of increasing a quality factor for a micromechanical resonator uses a laser beam to anneal the micromechanical resonator. In one embodiment, the micromechanical oscillator is formed by fabricating a mushroom shaped silicon oscillator supported by a substrate via a pillar. The laser beam is focused on a periphery of the mushroom shaped silicon oscillator to modify the surface of the mushroom shaped silicon oscillator. In a further embodiment, the mushroom shaped oscillator is a silicon disk formed on a sacrificial layer. Portions of the sacrificial layer are removed to free the periphery of the disk and leave a supporting pillar at the center of the disk. In further embodiments, different type resonators may be used.

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: 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 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 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: 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: A biological material sensing surface is exposed to a biological material that is selectively bound to a selected sensing portion of the sensing surface. The sensing surface is then subjected to shear stress oscillations to selectively remove nonspecifically bound material. The shear stress may be provided by an ultrasound resonator operating at a power sufficient to selectively remove nonspecifically bound biological material, such as protein from non-sensing areas of the sensing surface, which may be micropatterned array.

Abstract: Prefabricated catalyzing adsorption sites are incorporated into small oscillators. In one embodiment, the sites are formed of precisely positioned gold anchors on surface micromachined oscillators. The micromachined oscillators may be formed of silicon, such as polysilicon, or silicon nitride in various embodiments. The sites allow special control of chemical surface functionality for the detection of analytes of interest. Thiolate molecules may be adsorbed from solution onto the gold anchors, creating a dense thiol monolayer with a tail end group pointing outwards from the surface of the gold anchor. This results in a thiolate self-assembled monolayer (SAM), creating a strong interaction between the functional group and the gold anchor.

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 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: Position tracking of a receiving device within a gas or fluidic environment (for example a human body), is performed by measuring acoustic wave propagation parameters to provide real time, high precision telemetry. Multiple synchronized acoustic sources at different known locations transmit signals that are received by a receiver on the device to be located. The coordinates of the receiver can be determined by measuring a difference in the amplitude (coarse positioning) or phase (precise positioning) of the acoustic waves coming from different sources using triangulation calculations.