Abstract: A method for determining whether a subject has had a stroke and, if so, the type of stroke which includes analyzing the subject's body fluid for at least four selected markers of stroke, namely, myelin basic protein, S100 protein, neuronal specific enolase and a brain endothelial membrane protein such as thrombomodulin or a similar molecule. The data obtained from the analyses provide information as to the type of stroke, the onset of occurrence and the extent of brain damage and allow a physician to determine quickly the type of treatment required by the subject.

Abstract: An assay system and methods are described where patient samples containing genomic DNA are analyzed for the presence of known genetic polymorphisms using a universal reporter strategy. In a preferred embodiment, the amplified DNA is localized at test sites in an array of sites on a microchip followed by a series of hybridization reactions that screen for the presence of a single mutation from among a number of mutations, and allow the identification of specific mutations. In addition to universal reporters, the assay may use blockers and discriminators for screening and identification of known polymorphisms.

Abstract: A method and apparatus for addressing and driving an electrode array includes addressing one or more electrodes within the array using a plurality of row and column lines. In one aspect, a value corresponding to a voltage is stored in a local memory associated with each electrode. The addressed electrodes are then driven at the voltages corresponding to the stored values. In another aspect of the method, a driving element associated with each addressed electrode is selectively coupled with a voltage line so as to charge the electrode with the voltage on the voltage line. The device and methods may be used in the synthesis of biopolymers such as oligonucleotides and peptides.

Abstract: The present invention provides improved synthetic polymer hydrogel permeation layers for use on active electronic matrix devices for biological assays. The present invention includes methods for forming a permeation layer on an array of microelectrodes including the steps of attaching a linker to the surface of the array and providing a polymerization solution that includes a porogen. The surface of the array is then contacted with the polymerization solution and the polymerization solution is then polymerized on the surface of the array to form a permeation layer that is attached o the surface of the array through the linker. The porogen is then removed from the permeation layer, thereby creating void spaces in the permeation layer.

Abstract: This application includes methods for detecting single nucleotide polymorphisms (SNPs) in a sample using an electronically addressable microchip having a plurality of test sites. A sample nucleic acid is electronically biased, concentrated at, and immobilized to a test site on the microchip. A mixture comprising a first labeled probe and a second labeled probe is electronically hybridized to the sample nucleic acid to form first or second hybridized complexes. The first labeled probe is perfectly complementary to the first sample nucleic acid and the second labeled probe is complementary to the sample nucleic acid and contains a nucleotide that forms a mismatch with the nucleotide at the site of the polymorphism. The first or second hybridized complexes are detected by determining a signal intensity of the label of the first or second probe.

Abstract: A specific and sensitive in vitro ELISA assay and diagnostic test kit is disclosed for determining levels of NT-proBNP protein in a variety of bodily fluids, non-limiting examples of which are blood, serum, plasma, urine and the like. The NT-proBNP ELISA assay test employs the sandwich ELISA technique to measure circulating NT-proBNP in human plasma. In order to obtain antibodies with specific binding properties for targeted amino acid sequences within human proBNP, recombinant human proBNP (or rhproBNP) was expressed and purified for use as an immunogen. Polyclonal antibodies (PAb) to specific amino acid sequences were subsequently purified from goat serum by sequential affinity purification. Monoclonal antibodies were raised against specific polypeptides. Recombinant human NT-proBNP (or rhNT-proBNP) was expressed and purified in order to obtain material for use in calibration of a quantitative method for measurement of human NT-proBNP.

Abstract: The invention provides assay methods and kits that in general measure the level of a first analyte in a sample reduced by the level of a second analyte present in the same sample. In one embodiment, where levels of a first analyte from a first source is desirably determined and first analyte in the sample released from a second source is accompanied by proportional co-release of a second analyte, the assay identifies the level of first analyte released only from the first source. For analytes within bodily fluids, the assay can differentiate between elevated levels of analyte specific to the particular physiological or pathological state and elevated levels not specific to the particular state, providing single tests with diagnostic utility.

Abstract: A system useful in performing active biological reactions includes an array of unit cells arranged in rows and columns. Row lines are coupled to row contacts of unit cells of the array. A row selector is coupled to the row lines to provide a row select voltage. Column lines are coupled to column contacts of the array. A column selector is coupled to the column lines to provide more than two column voltage states on the column lines. The unit cells are coupled to a supply and to an electrode, the row select and column select voltage states provides variable current output from the electrode of the unit cell. A return electrode is coupled to a potential and adapted to contact conductive solution including charged biological materials, wherein in the presence of the conductive solution, current is provided between various unit cells and the return electrode.

Abstract: The instant invention involves the use of a combination of preparatory steps in conjunction with mass spectroscopy and time-of-flight detection procedures to maximize the diversity of biopolymers which are verifiable within a particular sample. The cohort of biopolymers verified within such a sample is then viewed with reference to their ability to evidence at least one particular disease state; thereby enabling a diagnostician to gain the ability to characterize either the presence or absence of said at least one disease state relative to recognition of the presence and/or the absence of said biopolymer, predict disease risk assessment, and develop therapeutic avenues against said disease.

Abstract: The instant invention involves the use of a combination of preparatory steps in conjunction with mass spectroscopy and time-of-flight detection procedures to maximize the diversity of biopolymers which are verifiable within a particular sample. The cohort of biopolymers verified within such a sample is then viewed with reference to their ability to evidence at least one particular disease state; thereby enabling a diagnostician to gain the ability to characterize either the presence or absence of at least one disease state relative to recognition of the presence and/or the absence of the biopolymer.

Abstract: A self-addressable, self-assembling microelectronic device is designed and fabricated to actively carry out and control multi-step and multiplex molecular biological reactions in microscopic formats. These reactions include nucleic acid hybridization, antibody/antigen reaction, diagnostics, and biopolymer synthesis. The device can be fabricated using both microlithographic and micro-machining techniques. The device can electronically control the transport and attachment of specific binding entities to specific micro-locations. The specific binding entities include molecular biological molecules such as nucleic acids and polypeptides. The device can subsequently control the transport and reaction of analytes or reactants at the addressed specific micro-locations. The device is able to concentrate analytes and reactants, remove non-specifically bound molecules, provide stringency control for DNA hybridization reactions, and improve the detection of analytes. The device can be electronically replicated.

Abstract: Methods for the transport and hybridization of a nucleic acid on an electrode device by providing a low conductivity buffer with a reducing agent to the device. The low conductivity buffer may also contain a zwitterion. A current and voltage is applied to a location of the device to effect electrophoretic transportation of the nucleic acid towards the location. The nucleic acid is then hybridized to a nucleic probed located at the location. The reducing agent in the low conductivity buffer may also be acting as a chaotropic agent.

Abstract: The instant invention involves the use of a combination of preparatory steps in conjunction with mass spectroscopy and time-of-flight detection procedures to maximize the diversity of biopolymers which are verifiable within a particular sample. The cohort of biopolymers verified within such a sample is then viewed with reference to their ability to evidence at least particular disease state; thereby enabling a diagnostician to gain the ability to characterize either the presence or the absence of at least one disease state relative to recognition of the presence and/or the absence of the biopolymer, predict disease risk assessment, and develop therapeutic avenues against the disease.

Abstract: In a method and a network for evaluating medical data in a clinical study, biochips containing patient samples with multiple biomolecular markers are tested in a number of point of care test devices respectively at point of care sites. Each test of each biochip sample produces a diagnostic result, which is entered into the electronic patient record for the patient who produced the sample. A follow-up examination is subsequently conducted for each patient, and the results of the follow-up examination are also entered into that patient's electronic patient record. The follow-up results indicate whether the diagnostic test result was a false positive, a false negative or correct. The follow-up data and the original diagnostic results from all point of care sites are electronically transmitted to a remote server, which has access to an expert system which uses the test results and the follow-up data to automatically devise a measurement protocol for a selected pathology.

Abstract: This invention pertains to the design, fabrication, and uses of an electronic system which can actively carry out and control multi-step and multiplex reactions in macroscopic or microscopic formats. In particular, these reactions include molecular biological reactions, such as nucleic acid hybridizations, nucleic acid amplification, sample preparation, antibody/antigen reactions, clinical diagnostics, combinatorial chemistry and selection, drug screening, oligonucleotide and nucleic acid synthesis, peptide synthesis, biopolymer synthesis, and catalytic reactions. A key feature of the present invention is the ability to control the localized concentration of two or more reaction-dependant molecules and their reaction environment in order to greatly enhance the rate and specificity of the molecular biological reaction.

Abstract: The instant invention involves the use of a combination of preparatory steps in conjunction with mass spectroscopy and time-of-flight detection procedures to maximize the diversity of biopolymers which are verifiable within a particular sample. The cohort of biopolymers verified within such a sample is then viewed with reference to their ability to evidence at least one particular disease state; thereby enabling a diagnostician to gain the ability to characterize either the presence or absence of at least one disease state relative to recognition of the presence and/or the absence of the biopolymer.

Abstract: The present invention provides improved synthetic polymer hydrogel permeation layers for use on active electronic matrix devices for biological assays. The present invention includes methods for forming a permeation layer on an array of microelectrodes including the steps of attaching a linker to the surface of the array by treating the surface with a linker by vapor deposition and providing a polymerization solution that includes at least one monomer having a polymerizable moiety, a modified streptavidin, a surfactant or porogen, and a cross-linking agent. The surface of the array is then contacted with the polymerization solution and the polymerization solution is then polymerized on the surface of the array to form a permeation layer that is attached o the surface of the array through the linker.

Abstract: The present invention is directed to devices and methods for carrying out and/or monitoring biological reactions in response to electrical stimuli. A programmable multiplexed active biologic array includes an array of electrodes coupled to sample-and-hold circuits. The programmable multiplexed active biologic array includes a digital interface that allows external control of the array using an external processor. The circuit may monitor, digitally control, and deliver electrical stimuli to the electrodes individually or in selected groups.

Abstract: The present invention provides a hand-held device of the type useful to perform an in vitro immunodiagnostic assay for an analyte of interest. In embodiments of the invention, the device incorporates a carrier for conducting the assay which comprises an array of pads including a sample pad, a narrow detection pad for detecting analyte, and a bridging pad coupled in flow communication therebetween. The device is provided with a housing adapted to deliver sample onto the carrier as a linear band having a width greater than the detection pad. In combination, these features yield a device that retains the sensitivity required for diagnostic accuracy, yet is improved in terms of cost and ease of manufacture.

Abstract: A diagnostic tool is disclosed for accurately and rapidly diagnosing the condition of an ailing organ. Although applicable to numerous organ and organ systems, this application particularly illustrates the concept of conjunctive marker utilization as it relates to diagnosing and distinguishing congestive heart failure. The invention particularly relates to the conjunctive utilization of cardiac Troponin I (cTn-I) and natriuretic peptide, e.g. ANP, pro-ANP, BNP, pro-BNP and CNP as a retrospective tool for diagnosing the underlying mechanism of heart failure and as a prospective analytical device for monitoring disease progression and efficacy of therapeutic agents.