Abstract: A sensor utilizing a non-leachable or diffusible redox mediator is described. The sensor includes a sample chamber to hold a sample in electrolytic contact with a working electrode, and in at least some instances, the sensor also contains a non-leachable or a diffusible second electron transfer agent. The sensor and/or the methods used produce a sensor signal in response to the analyte that can be distinguished from a background signal caused by the mediator. The invention can be used to determine the concentration of a biomolecule, such as glucose or lactate, in a biological fluid, such as blood or serum, using techniques such as coulometry, amperometry, and potentiometry. An enzyme capable of catalyzing the electrooxidation or electroreduction of the biomolecule is typically provided as a second electron transfer agent.

Abstract: The invention is to easily detect an interaction between nucleic acid and protein with high sensitivity without the need of sample labeling with a fluorescent molecule or sample anchorage onto a metal thin-film. As means for it, the presence or absence of occurrence of the interaction between nucleic acid and protein in a sample (S) is detected in an optical manner. Specifically, the sample (S) is irradiated with excitation rays (Le) and with measuring rays (L2) for measuring a photothermal effect produced in the sample (S) through the irradiation with the excitation rays (Le). A measurement signal for the photothermal effect in the sample (S) by the excitation rays (Le) is produced on the basis of any phase change of the measuring rays (L2). A temporal variation in the measurement signal is used for making a judgment on the presence or absence of any occurrence of interaction between nucleic acid and protein.

Abstract: An article such as a biosensor having a nonfouling surface thereon is described. The article comprises: (a) a substrate having a surface portion; (b) a linking layer on the surface portion; (c) a polymer layer comprising brush molecules formed on the linking layer; and (d) optionally but preferably, a first member of a specific binding pair (e.g., a protein, peptide, antibody, nucleic acid, etc.) coupled to the brush molecules. The polymer layer is preferably formed by the process of surface-initiated polymerization (SIP) of monomeric units thereon. Preferably, each of the monomeric units comprises a monomer (for example, a vinyl monomer) core group having at least one protein-resistant head group coupled thereto, to thereby form the brush molecule on the surface portion. Methods of using the articles are also described.

Abstract: A fluid delivery device includes an array of needles, each in fluid communication with a respective reservoir. Respective actuators are coupled so as to be operable to drive fluid from the reservoirs via needle ports. Each needle can have a plurality of ports, and the ports can be arranged to deliver a substantially equal amount of fluid at any given location along its length. A driver is coupled to the actuators to selectively control the rate, volume, and direction of flow of fluid through the needles. The device can simultaneously deliver a plurality of fluid agents along respective axes in solid tissue in vivo. If thereafter resected, the tissue can be sectioned for evaluation of an effect of each agent on the tissue, and based on the evaluation, candidate agents selected or deselected for clinical trials or therapy, and subjects selected or deselected for clinical trials or therapeutic treatment.

Abstract: The present invention provides a method and device for the improvement of intraplexed assays. This improvement is based upon the use of multiple assay chemistries having different affinity constants (KA) for an analyte. The overall assay displays high precision and predictable behavior because ratios between SMPCS-IDGs having different affinity constants (KA) change based on concentration. The advantages of the Applicant's improved system relative to the system of the '290 patent are that the improved system (1) further increases the statistical significance of results from assays applied to single well samples, (2) improves compensation for multiple sources of error, (3) makes possible further increased precision for each analyte, and (4) improves correlation between instruments, even if the instruments have significantly varying responses to an identical stimulus, (4) makes possible improved determination of a margin of error.

Abstract: A biofunctionalized nanoelectromechanical device (BioNEMS) for sensing single-molecules in solution by measuring the variation in the mechanical displacement of the BioNEMS device during a binding event is provided. The biofunctionalized nanoelectromechanical device according to the invention generally comprises a nanomechanical mechanical resonator, a detector integral with the mechanical resonator for measuring the mechanical displacement of the resonator, and electronics connected to the detector for communicating the results to a user. A system of biofunctionalized nanoelectromechanical devices and a method for utilizing the biofunctionalized nanoelectromechanical device of the present invention are also provided.

Abstract: A cell culture substrate having at least one area for culturing a cell on a substrate, characterized in that the culturing area comprises an area releasably holding a biologically active substance having a biological activity to the cell and an area for immobilizing a biologically active substance having a biological activity to the cell.

Abstract: The present invention relates to droplet-based surface modification and washing. According to one embodiment, a method of providing a bead-containing droplet with a reduced concentration of a substance is provided, the method including providing a droplet microactuator including a droplet having a starting volume and including one or more beads and a starting concentration and starting quantity of the substance. The method further includes conducting one or more droplet operations to merge a wash droplet with the droplet provided in the above step to yield a combined droplet and including one or more droplet operations to divide the combined droplet to yield a set of droplets including a droplet including substantially all of the one or more beads and having a decreased concentration of the substance relative to the starting concentration and a droplet which is substantially lacking in the beads.

Abstract: A method and apparatus for interrogating a target having a plurality of plasmon resonant particles (PREs) distributed in the target are disclosed. In the method, a field containing the target is illuminated, and one or more spectral emission characteristics of the light-scattering particles in the field are detected. From this data, an image of positions and spectral characteristic values in the field is constructed, allowing PREs with a selected spectral signature to be discriminated from other light-scattering entities, to provide information about the field. Also disclosed are a novel PRE composition for use in practicing the method, and a variety of diagnostic applications of the method.

Abstract: This invention generally relates to a methods, devices and kits for screening single cells for the production of one or more biologically active agents of interest, such as a protein, nucleic acid, or a protein and the nucleic acid encoding same.

Abstract: A multi-well system is described which is comprised of a tray comprising a plurality of wells which may include thousands, tens of thousands or even hundreds of thousands of wells or more. Each of the wells has a unique address. The system includes a tray top comprised of a plurality of areas wherein each of the areas corresponds uniquely to each of the wells and includes a unique address. The system may include a second tray top also comprised of a plurality of areas with unique addresses which uniquely correspond to each of the wells. The areas on the tops have compounds bound to those areas which compounds bind to components present in the wells and are used to obtain specific material in each well for analysis.

Abstract: An embodiment of a method for adjusting system gain of a biological probe array scanner for a plurality of fluorophore species is described that comprises setting an excitation beam comprising an excitation wavelength at a first power level that elicits an optimal signal to noise ratio response from a first fluorophore species; scanning a biological probe array with the excitation beam; setting the excitation beam comprising the excitation wavelength at a second power level different than the first power level that elicits the optimal signal to noise ratio response from a second fluorophore species; and scanning the biological probe array with the excitation beam.

Abstract: The present invention pertains to a device for binding a target entity onto a bait entity that is immobilized on said device, comprising: a) a lipid layer having a negative net charge in an aqueous solution at a neutral pH; b) a two-dimensional matrix of anchoring complexes that are bound to said lipid layer, wherein each of said anchoring complexes comprises: (i) a fusion complex comprising an Annexin protein fused to a partner molecule; and (ii) a bait entity. It also concerns various uses of said device, including for detection and pharmaceutical purposes.

Abstract: The invention described herein teaches methods of removing microvesicular particles, which include but are not limited to exosomes, from the systemic circulation of a subject in need thereof with the goal of reversing antigen-specific and antigen-nonspecific immune suppression. Said microvesicular particles could be generated by host cells that have been reprogrammed by neoplastic tissue, or the neoplastic tissue itself. Compositions of matter, medical devices, and novel utilities of existing medical devices are disclosed.

Abstract: A method and device are provided for stimulating and increasing the production of saliva during immunoassay tests for drugs or other analytes wherein a scent or odor capable of stimulating saliva production is incorporated into a device for obtaining an oral sample from a test subject. The scent or odor may be impregnated into the oral sample collection device or may be part of an attachment to such a device, and the scent or odor is disposed in such a manner so as to maximize the exposure of the scent to the test subject and thus stimulate the production of saliva. The method and device of the invention are advantageous because the increased production of saliva will facilitate the testing of an oral sample for drugs or other analytes and will increase the likelihood of obtaining a complete and accurate result.

Abstract: A cassette for fixing, embedding and slicing biological tissues includes a base sheet and a lid sheet formed of an elongated plastic sheet which is sliceable and has not less than predetermined strength. The base sheet has grooves as biological tissue receiving portions. The base plate and the lid sheet are formed by folding the plastic sheet along a fold line so that the lid sheet can be selectively opened and closed. Biological tissues are pressed against the bottoms of the grooves with pressing/retaining sponge members secured to the lid sheet at its portions corresponding to the respective grooves. In this state, the biological tissues are fixed by a fixing agent, and the cassette is dehydrated, infiltrated with paraffin as an embedding agent to embed the cassette, thereby forming a block including an embedding frame. The block is then sliced with a microtome to provide good biological tissue specimens.

Abstract: Systems and assay methods are disclosed for detecting an autoantibody in a sample. In certain instances, the systems and methods employ a mass tag releasably connected to an antigen. The tag is thereafter released for detection. A tag can be detected by mass spectrometry or in certain instances the tag is fluorescent. Methods for diagnosing a disease or disorder in a subject are also disclosed.

Abstract: A sensor utilizing a non-leachable or diffusible redox mediator is described. The sensor includes a sample chamber to hold a sample in electrolytic contact with a working electrode, and in at least some instances, the sensor also contains a non-leachable or a diffusible second electron transfer agent. The sensor and/or the methods used produce a sensor signal in response to the analyte that can be distinguished from a background signal caused by the mediator. The invention can be used to determine the concentration of a biomolecule, such as glucose or lactate, in a biological fluid, such as blood or serum, using techniques such as coulometry, amperometry; and potentiometry. An enzyme capable of catalyzing the electrooxidation or electroreduction of the biomolecule is typically provided as a second electron transfer agent.

Abstract: The present invention overcomes the problems and disadvantages associated with prior art arrays by providing an array comprising a plurality of biological membrane microspots associated with a surface of a substrate that can be produced, used and stored, not in an aqueous environment, but in an environment exposed to air under ambient or controlled humidities. Preferably, the biological membrane microspots comprise a membrane bound protein. Most preferably, the membrane bound protein is a G-protein coupled receptor, an ion channel, a receptor serine/threonine kinase or a receptor tyrosine kinase.

Abstract: The invention relates to methods and compositions for removing a dissociated species from a fluid medium solution during and after it has detached from a solid-phase immersed in said medium, thereby allowing the concentration of free species to remain close to zero, and for improving the signal to noise ratio in assays. This is achieved by employing a substrate, such as a scavenging solid-phase, having an attached binding partner or partners (“scavenger”) for the specifically binding species and which is present during storage. This substrate may also contain regions for binding signal generating components attached to the solid-phase. This substrate binds any free species bleeding off the solid phase, increasing the reliability and sensitivity of assays. A subset of the substrates in the invention additionally forms cross-linked networks of solid-phase particles that further increase the sensitivity of assays.