Abstract: The methods, systems 400 and apparatus disclosed herein concern metal 150 impregnated porous substrates 110, 210. Certain embodiments of the invention concern methods for producing metal-coated porous silicon substrates 110, 210 that exhibit greatly improved uniformity and depth of penetration of metal 150 deposition. The increased uniformity and depth allow improved and more reproducible Raman detection of analytes. In exemplary embodiments of the invention, the methods may comprise oxidation of porous silicon 110, immersion in a metal salt solution 130, drying and thermal decomposition of the metal salt 140 to form a metal deposit 150. In other exemplary embodiments of the invention, the methods may comprise microfluidic impregnation of porous silicon substrates 210 with one or more metal salt solutions 130. Other embodiments of the invention concern apparatus and/or systems 400 for Raman detection of analytes, comprising metal-coated porous silicon substrates 110, 210 prepared by the disclosed methods.

Abstract: Embodiments of the invention relate to integrated chemiluminescence devices and methods for monitoring molecular binding utilizing these devices and methods. These devices and methods can be used, for example, to identify antigen binding to antibodies. The devices include both a chemiluminescence material and a detector integrated together.

Abstract: The methods, systems 400 and apparatus disclosed herein concern metal 150 impregnated porous substrates 110, 210. Certain embodiments of the invention concern methods for producing metal-coated porous silicon substrates 110, 210 that exhibit greatly improved uniformity and depth of penetration of metal 150 deposition. The increased uniformity and depth allow improved and more reproducible Raman detection of analytes. In exemplary embodiments of the invention, the methods may comprise oxidation of porous silicon 110, immersion in a metal salt solution 130, drying and thermal decomposition of the metal salt 140 to form a metal deposit 150. In other exemplary embodiments of the invention, the methods may comprise microfluidic impregnation of porous silicon substrates 210 with one or more metal salt solutions 130. Other embodiments of the invention concern apparatus and/or systems 400 for Raman detection of analytes, comprising metal-coated porous silicon substrates 110, 210 prepared by the disclosed methods.

Abstract: Embodiments of the invention relate to integrated chemiluminescence devices and methods for monitoring molecular binding utilizing these devices and methods. These devices and methods can be used, for example, to identify antigen binding to antibodies. The devices include both a chemiluminescence material and a detector integrated together.

Abstract: Described are devices and methods for detecting binding on an electrode surface. In addition, devices and methods for electrochemically synthesizing polymers and devices and methods for synthesizing and detecting binding to the polymer on a common integrated device surface are described.

Abstract: Embodiments of the present invention provide microfluidic devices having deformable polymer membranes as components. The devices can be fabricated from a single polymeric block. Actuation of the membranes within the device allows the fluid contained within a microfluidic channel to be manipulated. Exemplary microfluidic devices, such as, peristaltic pumps, sample sorters, and flow stabilizers are described.

Abstract: Raman-active molecules having specific affinity for phosphorylated peptides and proteins are provided. The Raman-active affinity molecules contain a Raman active group capable of providing a detectable spectrum. The affinity molecules act as tags or reporter molecules and are useful, for example in detecting the presence of a phosphorylated residue in a peptide or protein through the use of SERS spectroscopy. The affinity molecules provide the ability to detect and quantify phosphatase and kinase activities.

Abstract: Methods for fabricating dense arrays of polymeric molecules in a highly multiplexed manner are provided using semiconductor-processing-derived methods and electrochemically generated reagents. Advantageously, the methods are adaptable to the synthesis of a variety of polymeric compounds. For example, arrays of peptides, polymers joined by peptide bonds, nucleic acids, and polymers joined by phosphodiester bonds may be fabricated in a highly multiplexed manner.

Abstract: The methods, systems 400 and apparatus disclosed herein concern metal 150 impregnated porous substrates 110, 210. Certain embodiments of the invention concern methods for producing metal-coated porous silicon substrates 110, 210 that exhibit greatly improved uniformity and depth of penetration of metal 150 deposition. The increased uniformity and depth allow improved and more reproducible Raman detection of analytes. In exemplary embodiments of the invention, the methods may comprise oxidation of porous silicon 110, immersion in a metal salt solution 130, drying and thermal decomposition of the metal salt 140 to form a metal deposit 150. In other exemplary embodiments of the invention, the methods may comprise microfluidic impregnation of porous silicon substrates 210 with one or more metal salt solutions 130. Other embodiments of the invention concern apparatus and/or systems 400 for Raman detection of analytes, comprising metal-coated porous silicon substrates 110, 210 prepared by the disclosed methods.

Abstract: The embodiments of the invention relate to a method for the introduction of a labeling structure such as a fluorescent molecules or a Raman tags to a compound. Imidazole functionalized resins or polymers are used to selectively immobilize phosphocompounds without protecting the carboxylic groups. Relying on the pKa difference between amines and hydrazides and carrying out the reaction in a slightly acidic buffer, all of the amines are protected by protonation while the hydrazides react with the phosphate imidazolide to form a phosphoramidate bond.

Abstract: The sensitivity of surface enhanced Raman spectroscopy to silver nano-particle/peptide aggregates is increased by prior treatment of the peptides. According to a first type of embodiment, an enzyme such as Glu-C is used for protein(s) digestion based on the enzyme's ability to cleave proteins at a selected location having a negative charge, such as at aspartic acid and glutamic acid. This type of digestion is used to derive a higher proportion of positively charged component peptides sequences as compared to the component peptides sequences obtained by standard tryptic digestion of protein(s). According to a second type of embodiment, methyl-esterification of peptides suppresses the negative charge contributions of portions of the peptides such as aspartic acid, glutamic acid, and the C-terminus. Both types of embodiments result in increased binding affinity of the resulting component sequence peptides with negatively charged nano-particles such as silver nano-particles.

Abstract: Metallic nanoclusters capable of providing an enhanced Raman signal from an organic Raman-active molecule incorporated therein are provided. The nanoclusters may be further functionalized, for example, with coatings and layers, such as adsorption layers, metal coatings, silica coatings, probes, and organic layers. The nanoclusters are generally referred to as COINs (composite organic inorganic nanoparticles) and are capable of acting as sensitive reporters for analyte detection. A variety of organic Raman-active compounds and mixtures of compounds can be incorporated into the nanocluster.

Abstract: The embodiments of the invention are directed to a SERS cluster comprising a capture particle that is at least partially surrounded by analyte molecules, wherein both the capture particle and the analyte molecules surrounding the capture particle are at least partially surrounded by enhancer particles, wherein a majority of the analyte molecules are either sandwiched between capture and enhancer particles or located between junctions of the enhancer particles. The embodiments of the invention also relate to methods of manufacturing and detecting the SERS cluster. The embodiments of the invention also relate to a SERS active particle comprising a tag molecule comprising a Raman active compound and a probe or a linker having a specific biochemical binding capability and to a method for detecting of a target molecule using a SERS active particle having a tag molecule comprising a Raman active compound and a probe or a linker.

Abstract: Microfluidic devices with porous membranes for molecular sieving, metering, and separation of analyte fluids. In one aspect, a microfluidic device includes a substrate having input and output microfluidic channel sections separated by a porous membrane formed integral to the substrate. In another aspect, the porous membrane may comprise a thin membrane that is sandwiched between upper and lower substrate members. The microfluidic device may include one or a plurality of porous membranes. In one embodiment, a plurality of porous membranes having increasingly smaller pores are disposed along portions of a microfluidic channel. In another embodiment, a cascading series of upper and lower channels are employed, wherein each upper/lower channel interface is separated by a respective porous membrane. In another aspect, a porous membrane is rotatably coupled to a substrate within a microfluidic channel via a MEMS actuator to enable the porous membrane to be positioned in filtering and pass-through positions.

Abstract: A SERS active particle having a metal-containing particle and a cationic coating on the metal-containing particle, wherein the SERS active particle carries a positive charge is disclosed. Also, a SERS active particle having a metal-containing particle and a non-metallic molecule, wherein the metal-containing particle is derivatized with the non-metallic molecule is disclosed. In addition, several methods of modifying the nanoparticles surfaces of a SERS active particle and of improving the interaction between the SERS active particle and an analyte are disclosed.

Abstract: Embodiments of the present invention provide methods for determining the degenerate binding capabilities of antibodies. The methods provide information about degenerate binding capabilities without the use of involved procedures. Optionally, a molecule toward which an antibody exhibits degenerate binding ability may be identified through the use of a reporter, such as, a composite organic inorganic nanocluster (COIN). COINs are sensitive SERS (surface enhanced Raman spectroscopy) reporters capable of multiplex analysis of analytes.

Abstract: Embodiments of the invention relate to integrated chemiluminescence devices and methods for monitoring molecular binding utilizing these devices and methods. These devices and methods can be used, for example, to identify antigen binding to antibodies. The devices include both a chemiluminescence material and a detector integrated together.

Abstract: Embodiments of the invention relate to detecting binding of a first analyte to a second analyte by Raman spectroscopy. An embodiment includes attaching one analyte to a substrate and then detecting the binding of another analyte to the analyte on the substrate by Raman spectroscopy. Another embodiment includes contacting analytes in a fluid and then detecting the binding of one analyte to another analyte by Raman spectroscopy.

Abstract: Methods for fabricating dense arrays of polymeric molecules in a highly multiplexed manner are provided using semiconductor-processing-derived lithographic methods. Advantageously, the methods are adaptable to the synthesis of a variety of polymeric compounds. For example, arrays of peptides and polymers joined by peptide bonds may be fabricated in a highly multiplexed manner.

Abstract: Methods for fabricating dense arrays of polymeric molecules in a highly multiplexed manner are provided using semiconductor-processing-derived lithographic methods. Advantageously, the methods are adaptable to the synthesis of a variety of polymeric compounds. For example, arrays of peptides and polymers joined by peptide bonds may be fabricated in a highly multiplexed manner.