Integrated Biosensor and Simulation System for Diagnosis and Therapy
First Claim
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1. Integrated biosensor platform comprising:
- a multifunctional array; and
a detection system comprising a plurality of biosensors coupled to the multifunctional array including a DNA sensor, an RNA sensor, a peptide or protein sensor, an antibody sensor, an antigen sensor, a tissue factor sensor, a vector or virus vector sensor, a lipid or fatty acid sensor, a steroid sensor, a neurotransmitter sensor, an inorganic ion or electrochemical sensor, a pH sensor, a free radical sensor, a carbohydrate sensor, a neural sensor, a chemical sensor, a small molecule sensor, an exon sensor, a metabolites sensor, an intermediate sensor, a chromosome sensor, and a cell sensor.
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Abstract
BioMEMS/NEMS appliance biologically monitors an individual, using biosensors to detect cellular components. Data is simulated or analyzed using systems-biology software, which provides diagnostic or therapeutic guidance.
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Citations
107 Claims
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1. Integrated biosensor platform comprising:
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a multifunctional array; and a detection system comprising a plurality of biosensors coupled to the multifunctional array including a DNA sensor, an RNA sensor, a peptide or protein sensor, an antibody sensor, an antigen sensor, a tissue factor sensor, a vector or virus vector sensor, a lipid or fatty acid sensor, a steroid sensor, a neurotransmitter sensor, an inorganic ion or electrochemical sensor, a pH sensor, a free radical sensor, a carbohydrate sensor, a neural sensor, a chemical sensor, a small molecule sensor, an exon sensor, a metabolites sensor, an intermediate sensor, a chromosome sensor, and a cell sensor. - View Dependent Claims (2)
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3. System biology platform comprising:
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means for verifying, modeling and simulating genomics, proteomics, computational chemistry, pharmacogenomics, computational biology, computational biophysics, computational cell behavior, pharmacokinetics, metabolomics, and trnscriptomics; and means for sensing coupled to the verifying, modeling and simulating means. - View Dependent Claims (4, 5)
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6. Therapeutic apparatus comprising:
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a therapeutic manufacture; a therapeutic reservoir; and a sensor manufacture. - View Dependent Claims (7, 8, 9)
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10. DNA unit comprising:
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a DNA sensor; a DNA therapeutic manufacture; and a sensor manufacture.
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11. Computer-assisted method for diagnosis/therapy comprising steps:
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pre-diagnosing; preliminary modeling; configuring a biosensor; implanting the biosensor; initializing a chip in vivo; program executing; initial in vivo sensing; in vivo modeling; and recommending diagnosis or therapy. - View Dependent Claims (12, 13)
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14. A systems biology platform for computational modeling and simulation of multi-cellular systems or unicellular systems comprising:
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internal or external databases, wherein the databases comprise genomics database, protein database, gene expression database, transcriptomics database, proteomics database, metabolomics database, pharmacogenomics database, pharmacokinetics database, disease database or drug database; bioinformatics analysis tools, wherein the bioinformatics analysis tools comprise network inference, sequence analysis or protein folding; a set of mathematics equations, wherein the mathematics equations represent biological processes of multi-cellular or unicellular systems; and computational software to support the said systems biology platform; wherein such computational software accesses one or more databases, applies one or more mathematics equations and operates one or more bioinformatics analysis tools to integrate data from multi-cellular or unicellular systems at a system level, thereby aiding to understand the interrelationships and functional organization of cells and genomes, whereby monitoring or analyzing biological hosts and providing diagnostic or therapeutic guidance on cancer studies or diseases, organ generation, and drug development. - View Dependent Claims (15, 16, 17, 18, 19, 20, 21, 22, 23, 24)
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25. A computational software-based method for modeling and simulating multi-cellular or unicellular systems comprising the steps of:
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collecting biological data from multi-cellular or unicellular systems via one or more biosensors; storing and retrieving the biological data in corresponding databases, wherein the databases may be internal or external, and may be accessed locally or remotely via wired or wireless network communications, whereby the databases comprise genomics database, protein database, gene expression database, transcriptomics database, proteomics database, metabolomics database, pharmacogenomics database, pharmacokinetics database, disease database or drug database; representing one or more biological processes in mathematical formats by using one or more mathematics equations; running one or more bioinformatics analysis tools to analyze and simulate the biological data from multi-cellular or unicellular systems; and generating diagnostic or therapeutic guidance on cancer studies or diseases, organ generation, and drug development. - View Dependent Claims (26, 27, 28, 29, 30, 31)
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32. A method for predicting the complete genome of a host comprising:
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inputting biological material in the form of a single cell to a multifunctional biosensor wherein the multifunctional biosensor senses biological materials from the single cell wherein the biological materials are selected from a group comprising concentrations, inorganic or organic materials, cellular material, genetic material, nucleic acids, proteins, amino acids, peptides, antibodies, antigens, fatty acids, lipids, steroids, neurotransmitters, inorganic ions, pH levels, free radicals, carbohydrates, chemicals, small molecules, cells, tissue, pharmaceuticals, toxins, metabolites, and physiological levels; receiving data from a multifunctional biosensor; accessing a systems biology platform via a network to model biological processes based on one or more genomic sequences of the host, wherein the systems biology platform comprises of one or more of genomics database, transcriptomics database, proteomics database, metabolomics database, or disease database; running a set of simulations based on data in the models; comparing data obtained from said multifunctional biosensor platform with the results of said simulations; and generating a report predicting the genomic sequence or structure of the host. - View Dependent Claims (33, 34, 35)
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36. A method for predicting the complete genome of a host comprising:
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inputting biological material in the form of a single cell to a multifunctional biosensor platform wherein the multifunctional biosensor senses data from one or more of deoxyribonucleic acid sensor, exon sensor, or chromosome sensor; receiving genomic or genetic sequence data of a single cell of the host from the multifunctional biosensor; accessing a systems biology platform via a network to model the genome of the host based on a genomics database in the systems biology platform and data received from said multifunctional biosensor platform; and using one or more of pattern recognition, feature extraction, supervised learning, unsupervised learning, learning algorithms, neural networks, artificial intelligence or fuzzy systems to reconstruct the genomic sequence of the host. - View Dependent Claims (37, 38, 39)
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40. A network system for predicting the genomic sequence of a subject comprising:
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a multifunctional biosensor comprising one or more of deoxyribonucleic acid sensor, exon sensor, or chromosome sensor; a processor; a memory comprising genomics database; and means for transmitting information obtained by said biosensor to the processor; wherein the processor compares genomic data of the subject received from inputting biological material to the biosensor, to genomic data from genomics database and utilizes predictive or comparative algorithms to predict the genomic sequence of the subject.
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41. A method for predicting the metabolic output of an organism comprising:
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inputting biological material to a multifunctional biosensor platform wherein the multifunctional biosensor senses and provides data on biological materials selected from, concentrations, inorganic or organic materials, cellular material, genetic material, nucleic acids, proteins, amino acids, peptides, antibodies, antigens, fatty acids, lipids, steroids, neurotransmitters, inorganic ions, pH levels, free radicals, carbohydrates, chemicals, small molecules, cells, tissue, pharmaceuticals, toxins, metabolites, or physiological levels; receiving data from a multifunctional biosensor; representing one or more biological processes or molecular interactions as mathematical models; accessing a systems biology platform via a network to model biological processes based on genomic sequences, wherein the systems biology platform comprises of one or more of genomics database, transcriptomics database, proteomics database, or metabolomics database; running a set of simulations based on data and the administration of a substance or manipulation of the organism; comparing data obtained from said multifunctional biosensor platform with the results of said simulations; and generating a simulation report for predicting the metabolic out come of the administration of a substance or manipulation of the organism to aid in the bio-manufacturing or biopharming of the substance.
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42. A method for evaluating drug toxicity in a biological system comprising the steps of:
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administering a drug to the biological system; monitoring one or more responses of the biological system to said drug using one or more sensors; accessing a systems biology platform via a network to said sensor(s), wherein the systems biology platform comprises a genomics database, a transcriptomics database, a metabolomics database, a pharmacogenomics database, pharmacokinetics database or a drug database; implementing knowledge-based techniques from the systems biology platform to analyze data from said one or more sensors; and generating a report evaluating toxicity of the drug administered to the biological system. - View Dependent Claims (43, 44)
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45. A network system for evaluating drug toxicity in a biological host comprising:
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a processor and a memory wherein the memory represents mathematically, via the network, genomic, transcriptomic, metabolomic, or pharmacogenomic data; and
the processor runs one or more simulations to evaluate toxicity of one or more drugs in the biological host. - View Dependent Claims (46)
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47. An operator-independent network system for diagnosing or making therapy recommendation comprising:
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a non-implantable or implantable networked biosensor for monitoring cardiac performance, blood flow, blood metabolites, antigen, antibody, viruses, hormones, neurotransmitter, pH, free radical, carbohydrate, proteins, or small molecules such that physiological conditions of the individual are determined; a processor using mathematical methods comprising neural networks, artificial intelligence, fuzzy systems, or probabilities on the patient records to simulate one or more conditions of a patient; a network database comprising systems biology platform wherein the systems biology platform comprises genomics database, proteomics database, pharmaco-genomic database, chemical compound database etc.; and a data analysis module or a set of computer readable instructions for providing immediate actionable physiologic feedback and reporting one or more diagnoses or therapy recommendation based on the physiological condition of the patient to a medical professional.
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48. A method for diagnosing or making therapy recommendation comprising the steps of:
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using a non-implantable or implantable sensor for monitoring cardiac performance, blood flow, blood metabolites, antigen, antibody, viruses, hormones, neurotransmitter, pH, free radical, carbohydrate, proteins, or small molecules such that physiological conditions of the individual are determined; using mathematical methods comprising neural networks, artificial intelligence, fuzzy systems, or probabilities on the patient records to simulate one or more conditions of a patient; and reporting one or more diagnoses or therapy recommendations based on the condition of the patient, to a medical professional on a user interface connected to a network.
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49. An apparatus for diagnosing an individual or for making therapy recommendation comprising:
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a non-implantable or implantable biosensor for monitoring cardiac performance, blood flow, blood metabolites, antigen, antibody, viruses, hormones, neurotransmitter, pH, free radical, carbohydrate, proteins, or small molecules such that physiological conditions of the individual are determined; a data analyzer or a set of computer readable instructions for providing immediate actionable physiologic feedback; and a user interface integrated to a network for accessing or for reporting one or more diagnoses or therapy recommendation based on the physiological condition of the patient to a medical professional.
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50. An apparatus for monitoring a patient'"'"'s metabolic profile comprising of:
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a non-implantable or implantable sensor comprising of biological microelectromechanical sensor (MEMS) chip or detection or transducer device that may be implemented or computer-modeled for operation in silicon, silica, glass, polymer or other substrate or instrumentation cavity, beam, surface, channel, encapsulated molecules, membrane, quantum dot or nanocrystal, matrix or array for single or multi-channel independent signal detection in two or three dimensions in vitro or in vivo for monitoring blood flow, blood metabolites, antigen, antibody, viruses, hormones, neurotransmitter, pH, free radical, carbohydrate, proteins, or small molecules; a processor for providing immediate actionable physiologic feedback; and a user interface integrated to a network for accessing or for generating report such that one or more diagnosis or therapy recommendations can be made based on the condition of the patient. - View Dependent Claims (51)
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52. An apparatus for monitoring cardiac and hemodynamic effect on the patient, comprising of:
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a non-implantable or implantable biosensor for monitoring cardiac performance, blood flow, pulse, myocardial wall contractility, arterial blood pressure, or oxygen content in right atrium of a patient to assess circulation to organ after transplant or reconstructive surgery; a processor for analyzing and transmitting monitoring blood flow, pulse, myocardial wall contractility, arterial blood pressure, or oxygen content in right atrium data in a computer readable set of instructions; and a user interface integrated to a network for accessing the cardiac and hemodynamic performance from a database coupled to the processor, and making therapy recommendations to a medical professional.
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53. A drug discovery system comprising:
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a high-throughput capability to generate crystals of a target protein; a library of protein molecular fragments; one or more computational design methods; and one or more iterative synthetic chemistry; wherein the computational design methods and the iterative synthetic chemistry optimize the protein molecular fragments into one or more drug-like lead compounds. - View Dependent Claims (54, 55)
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56. A method for drug discovery, the method comprising:
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generating crystals of a target protein via a high-throughput capability; maintaining a library of protein molecular fragments; developing one or more computational design methods; and developing one or more iterative synthetic chemistry; wherein the computational design methods and the iterative synthetic chemistry optimize the protein molecular fragments into drug-like lead compounds. - View Dependent Claims (57, 58)
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59. A method for making therapy recommendations comprising:
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receiving information of prescription or dosage of a patient; genotyping single nucleotide polymorphisms of the patient based on prescription or dosage; storing information in a database such that patient records comprising reports indicating diet, present medications, family history of disease, or environmental or immunological factors is accessible using an on-screen search of a patient record; and reporting therapy recommendations to a patient'"'"'s healthcare provider.
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60. A method for analysis and interpretation of pharmacokinetic data comprising:
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determining one or more interaction factors between a potential drug molecule and a biological molecule wherein the interaction factors comprise sterics, charge, or dipole forces; predicting pharmacokinetic interactions between the potential drug molecule and the biological molecule; statistically assessing the pharmacokinetic data; and pharmacokinetic modeling for proving the therapeutic value of the drug molecule as a new pharmaceutical or generic drug.
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61. A method of centralized comprehensive data-management comprising:
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electronic remote data capture and scanning and indexing through; data validation and review to promote data integrity through coordination with data managers, clinical personnel, and programmers; and use of data to provide therapy, diagnosis, or other automated feedback. - View Dependent Claims (62)
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63. A method comprising:
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sensing one or more biological molecules wherein the biological molecules comprise organic or inorganic substances, cells, tissue, nutrients, chemicals, intracellular materials, extra-cellular materials, charged ions, pharmaceuticals, or molecular materials affecting host physiology and wherein the biological molecules may be accessed from a group comprising of plasma, serum, urine, cerebrospinal fluid, tissue, xenograft and cell lines; screening one or more biomarkers by mass spectrometry-based proteomics and metabolomics; and identifying useful biological markers to create a better understanding of disease and therapeutic response.
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64. A method for identification of relevant biomolecules comprising:
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tandem mass spectrometry to establish one or more structural characteristics of a peptide or protein biomolecule; and identification of one or more post-translational modifications including unusual proteolytic processing and mutations in proteins with a label-free method that provides differential quantification and molecular identification.
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65. A computerized method comprising:
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profiling one or more chemical compounds; identifying the said one or more compounds as therapeutic targets; prioritizing the said therapeutic targets; implementing data-based techniques wherein the data-based techniques comprise decision theory, pattern recognition, or Bayesian analysis or knowledge-based techniques wherein the knowledge-based techniques comprise mathematical modeling, simulation or symbolic reasoning; analyzing one or more mechanisms of toxicity of the said one or more compounds; and generating a report about toxicity and safety assessment of the one or more compounds.
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66. A method for integrated biosensor and simulation system comprising:
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obtaining biological data from one or more biosensors; identifying and prioritizing one or more biomarkers via analysis of gene expression arrays, proteomics, or genotyping data; correlating one or more molecular events to higher-order cellular and disease processes; and generating a report showing relevance to organismal physiology and pathophysiology. - View Dependent Claims (67, 68)
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69. A computerized method for evaluating toxicity and safety comprising:
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correlating one or more gene expression data to one or more clinical pathologies; identifying one or more mechanisms of toxicity of one or more chemical compounds; analyzing pharmacological response, mechanism of action, or mechanism of toxicity; and generating a report about biological responses in the liver, kidney, or heart of a biological host to the one or more chemical compounds, thereby evaluating their toxicity or safety. - View Dependent Claims (70, 71)
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72. A network system based molecular phenotype diagnosis station comprising:
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a multichannel assay block wherein the multichannel assay block generates a fingerprint of a molecular phenotype from a host for one or more biomarkers selected from a group of lipids, proteins, carbohydrates and nucleic acids; an indicator; and a processor wherein the processor compares the molecular phenotype of the host to a database and generates a sub-phenotype associated with a disease of a host and causes a display to indicate a molecular phenotype and a sub-phenotype associated with a disease of a host. - View Dependent Claims (73, 74)
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75. In an network system comprising a processor, a multichannel assay block, and a indicator, a diagnosis method comprising:
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submitting a biological sample from a host to the multichannel assay block wherein the biological sample is selected from a group of lipids, proteins, carbohydrates and nucleic acids; analyzing the submitted sample in an assay to generate an assay result; and converting the assay result into a molecular phenotype or sub-phenotype for a disease of the host. - View Dependent Claims (76, 77, 78, 79, 80)
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81. A network based molecular phenotype diagnosis system comprising:
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a processor; a multichannel assay block; a memory; and an indicator wherein the processor accepts data from a multichannel assay block, converts the data from the multichannel assay block to one or more fingerprint molecular phenotypes, saves the fingerprint molecular phenotypes in memory, accesses data from memory and compares with each other and generates a molecular sub-phenotype as the diagnosis, saves the diagnosis in the memory and sends to display on the indicator as one or more molecular phenotype associated with the disease of the host. - View Dependent Claims (82, 83, 84)
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85. A method for genotyping comprising:
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applying PCR to amplify target DNA; extending a primer used in PCR to detect sequence differences at the single nucleotide level; and performing SELDI MS analysis of the primer extension products to detect one or more disease markers. - View Dependent Claims (86, 87)
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88. A method for quantitative gene expression comprising:
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reverse transcribing RNA to complementary DNA; applying real-time PCR to amplify the complementary DNA; performing single base primer extension; and performing SELDI MS analysis of the primer extension products to identify one or more disease biomarkers. - View Dependent Claims (89, 90, 91, 92)
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93. A method for quantitative DNA methylation comprising:
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applying bisulfite treatment to target DNA; applying PCR to amplify treated target DNA; performing RNA transcription and base specific RNA cleavage; and performing SELDI MS analysis on cleavage products to identify one or more disease biomarkers.
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94. A system for quantitative and qualitative applications for genetic research wherein:
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SELDI ProteinChip interface and TOF tandem mass spectrometer provide automatic data acquisition; and software modules provide automatic quantitative and qualitative analysis.
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95. A sensor and an analysis method comprising:
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implanting or attaching one or more biosensors to a biological host; sensing native or foreign substances in the host wherein the substances comprise small molecules, metabolites, intermediates, toxins, pharmaceuticals, vitamins, minerals, or other organic or inorganic chemicals; communicating electrical, electronic, or electromagnetic signals via a network server to a systems biology platform wherein the systems biology platform comprises computer equipment, software programs, or reconfigurable firmware or emulation logic devices to verify, model, simulate, or analyze stored or raw data using computational biology or other analysis software or hardware tools; generating a report of the effectiveness or side effects of one or more therapies in the host; and administering one or more therapies to the host. - View Dependent Claims (96)
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97. A sensor and analysis method comprising:
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inserting a biosensor in a model system; sensing native or foreign substances in the model system wherein the substances comprise small molecules, metabolites, intermediates, toxins, pharmaceuticals, vitamins, minerals, or other organic or inorganic chemicals; communicating electrical, electronic, or electromagnetic signals via a network server to a systems biology platform wherein the systems biology platform comprises computer equipment, software programs, or reconfigurable firmware or emulation logic devices to verify, model, simulate, or analyze stored or raw data using computational biology or other analysis software or hardware tools; and generating a report of the effectiveness or side effects of one or more therapies in the model system.
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98. DNA unit for molecular diagnostics comprising:
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a DNA sensor; a DNA therapeutic manufacture; and a sensor manufacture; wherein a systems-biology platform causes the DNA sensor to sense an organism in-vivo in response to the DNA therapeutic or sensor manufacture dispensing therapy material in the organism, the systems-biology platform monitoring the DNA sensor according to one or more systems-biology models to diagnose automatically the organism and cause the DNA therapeutic or sensor manufacture to generate a therapy manufacture. - View Dependent Claims (99, 100, 101, 102)
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103. In a DNA unit including a DNA sensor, a DNA therapeutic manufacture, and a sensor manufacture, a method for molecular diagnostics comprising steps:
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sensing by the DNA sensor an organism in-vivo in response to the DNA therapeutic or sensor manufacture dispensing therapy material in the organism; monitoring by a systems-biology platform the DNA sensor according to one or more systems-biology models to diagnose automatically the organism and thereby cause the DNA therapeutic or sensor manufacture to generate a therapy manufacture. - View Dependent Claims (104, 105, 106, 107)
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Specification