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 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 present invention provide devices and methods for detecting, identifying, distinguishing, and quantifying modification states of peptides using Surface Enhanced Raman Spectroscopy (SERS) and Raman spectroscopy. Additional embodiments provide strategies for chemically derivatizing post-translational modifications and detecting the chemically derivatized products using SERS. Applications of embodiments of the present invention include proteome wide modification profiling and analyses with applications in disease diagnosis, prognosis and drug efficacy studies, enzymatic activity profiling and assays.

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: Embodiments of the present invention provide devices and methods for detecting, identifying, distinguishing, and quantifying modification states of proteins and peptides using Surface Enhanced Raman (SERS) and Raman spectroscopy. Applications of embodiments of the present invention include, for example, proteome wide modification profiling and analyses with applications in disease diagnosis, prognosis and drug efficacy studies, enzymatic activity profiling and assays.

Abstract: Embodiments of the present invention provide microfluidic devices containing deformable polymer membranes. 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 mixers are described.

Abstract: The methods and apparatus disclosed herein concern nucleic acid sequencing by enhanced Raman spectroscopy. In certain embodiments of the invention, nucleotides are covalently attached to Raman labels before incorporation into a nucleic acid 13. Exonuclease 15 treatment of the labeled nucleic acid 13 results in the release of labeled nucleotides 16, 130, which are detected by Raman spectroscopy. In alternative embodiments of the invention, nucleotides 16, 130 released from a nucleic acid 13 by exonuclease 15 treatment are covalently cross-linked to silver or gold nanoparticles 140 and detected by surface enhanced Raman spectroscopy (SERS), surface enhanced resonance Raman spectroscopy (SERFS) and/or coherent anti-Stokes Raman spectroscopy (CARS). Other embodiments of the invention concern apparatus 10, 100, 210 for nucleic acid sequencing.

Abstract: Embodiments of the present invention provide devices and methods for detecting, identifying, distinguishing, and quantifying modifications to nucleic acids, proteins, and peptides using SERS and Raman spectroscopy. Applications of embodiments of the present invention include proteome wide modification profiling and analyses with applications in disease diagnosis, prognosis and drug efficacy studies, enzymatic activity profiling and assays.

Abstract: The methods and apparatus disclosed herein concern nucleic acid sequencing by enhanced Raman spectroscopy. In certain embodiments of the invention, nucleotides are covalently attached to Raman labels before incorporation into a nucleic acid 13. Exonuclease 15 treatment of the labeled nucleic acid 13 results in the release of labeled nucleotides 16, 130, which are detected by Raman spectroscopy. In alternative embodiments of the invention, nucleotides 16, 130 released from a nucleic acid 13 by exonuclease 15 treatment are covalently cross-linked to silver or gold nanoparticles 140 and detected by surface enhanced Raman spectroscopy (SERS), surface enhanced resonance Raman spectroscopy (SERRS) and/or coherent anti-Stokes Raman spectroscopy (CARS). Other embodiments of the invention concern apparatus 10, 100, 210 for nucleic acid sequencing.

Abstract: Methods and devices for immobilizing and isolating single polymeric molecules are disclosed. In some aspects, controllable dispensing of target polymeric molecules is provided. In additional aspects of the invention, methods for creating and manipulating microbeads having a single target nucleic acid molecule attached are provided. Aspects of the disclosed devices and methods are exemplified using microfluidics.

Abstract: Methods and devices for immobilizing single polymeric molecules are disclosed. A method for isolating a single polymeric molecule comprises contacting polymeric molecules with agents under conditions that permit formation of agent-polymeric molecule complexes, said polymeric molecules immobilized at positions on a substrate separated by at least about two times the length of the polymeric molecules, said agents comprising a binding partner having binding affinity for a label of the polymeric molecules, and releasing at least one of the agent-polymeric molecule complexes from the substrate to isolate a single polymeric molecule.

Abstract: A novel device and method for characterization of molecules is provides that improves characterization accuracy by utilizing larger numbers of reactive molecules that are smaller or shorter in chain length for the analysis procedure. Modification of markers such as nanotubes form nanotube assemblies that are easily detected using a number of surface analysis devices such as AFM and STM. The novel method shown using carbon nanotubes to mark a signature on reactive molecules permits a larger distribution and smaller molecule size of reactive molecules used in characterization of a sample molecule. The modification of the carbon nanotubes allows the characterization procedure to detect the nanotube markers more easily, thus decreasing characterization errors, and allowing faster characterization speeds.

Abstract: Microfluidic apparatus including integrated porous substrate/sensors that may be used for detecting targeted biological and chemical molecules and compounds. In one aspect, upper and lower microfluidic channels are defined in respective halves of a substrate, which are sandwiched around a porous membrane upon assembly. In other aspect, the upper and lower channels are formed such that a portion of the lower channel passes beneath a portion of the upper channel to form a cross-channel area, wherein the membrane is disposed between the two channels. In various embodiments, one or more porous membranes are disposed proximate to corresponding cross-channel areas defined by one or more upper and lower channels. The porous membrane may also have sensing characteristics, such that it produces a change in an optical and/or electronic characteristic.

Abstract: The present methods and apparatus 100 concern nucleic acid 214 sequencing by incorporation of nucleotides 218 into nucleic acid strands 220. The incorporation of nucleotides 218 is detected by changes in the mass and/or surface stress of the structure 116, 212. In some embodiments of the invention, the structure 116, 212 comprises one or more nanoscale or microscale cantilevers. In certain embodiments of the invention, each different type of nucleotide 218 is distinguishably labeled with a bulky group and each incorporated nucleotide 218 is identified by the changes in mass and/or surface stress of the structure 116, 212 upon incorporation of the nucleotide 218. In alternative embodiments of the invention only one type of nucleotide 218 is exposed at a time to the nucleic acids 214, 220. Changes in the properties of the structure 116, 212 may be detected by a variety of methods, such as piezoelectric detection, shifts in resonant frequency of the structure 116, 212, and/or position sensitive photodetection.

Abstract: Microfluidic apparatus including integrated porous substrate/sensors that may be used for detecting targeted biological and chemical molecules and compounds. In one aspect, upper and lower microfluidic channels are defined in respective halves of a substrate, which are sandwiched around a porous membrane upon assembly. In another aspect, the upper and lower channels are formed such that a portion of the lower channel passes beneath a portion of the upper channel to form a cross-channel area, wherein the membrane is disposed between the two channels. In various embodiments, one or more porous membranes are disposed proximate to corresponding cross-channel areas defined by one or more upper and lower channels. The porous membrane may also have sensing characteristics, such that it produces a change in an optical and/or electronic characteristic.

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: Microfluidic apparatus including integrated porous substrate/sensors that may be used for detecting targeted biological and chemical molecules and compounds. In one aspect, upper and lower microfluidic channels are defined in respective halves of a substrate, which are sandwiched around a porous membrane upon assembly. In another aspect, the upper and lower channels are formed such that a portion of the lower channel passes beneath a portion of the upper channel to form a cross-channel area, wherein the membrane is disposed between the two channels. In various embodiments, one or more porous membranes are disposed proximate to corresponding cross-channel areas defined by one or more upper and lower channels. The porous membrane may also have sensing characteristics, such that it produces a change in an optical and/or electronic characteristic.

Abstract: Disclosed herein is an apparatus that includes a body structure having a plurality of microfluidic channels fabricated therein, the plurality of microfluidic channels comprising a center channel and focusing channels in fluid communication with the center channel via a plurality of cascaded junctions. Also disclosed herein is a method that includes the step of providing a body structure having a plurality of microfluidic channels fabricated therein, the plurality of microfluidic channels comprising a center channel and focusing channels in fluid communication with the center channel via a plurality of cascaded junctions. The method also includes the steps of providing a flow of the sample fluid within the center channel, providing flows of sheath fluid in the focusing channels, and controlling or focusing the flow of the sample fluid by adjusting the rate at which the sheath fluid flows through the focusing channels and cascaded junctions, and into the center channel.

Abstract: The present methods and apparatus 100 concern nucleic acid 214 sequencing by incorporation of nucleotides 218 into nucleic acid strands 220. The incorporation of nucleotides 218 is detected by changes in the mass and/or surface stress of the structure 116, 212. In some embodiments of the invention, the structure 116, 212 comprises one or more nanoscale or microscale cantilevers. In certain embodiments of the invention, each different type of nucleotide 218 is distinguishably labeled with a bulky group and each incorporated nucleotide 218 is identified by the changes in mass and/or surface stress of the structure 116, 212 upon incorporation of the nucleotide 218. In alternative embodiments of the invention only one type of nucleotide 218 is exposed at a time to the nucleic acids 214, 220. Changes in the properties of the structure 116, 212 may be detected by a variety of methods, such as piezoelectric detection, shifts in resonant frequency of the structure 116, 212, and/or position sensitive photodetection.

Abstract: The methods and apparatus disclosed herein concern nucleic acid sequencing by enhanced Raman spectroscopy. In certain embodiments of the invention, nucleotides are covalently attached to Raman labels before incorporation into a nucleic acid 13. Exonuclease 15 treatment of the labeled nucleic acid 13 results in the release of labeled nucleotides 16, 130, which are detected by Raman spectroscopy. In alternative embodiments of the invention, nucleotides 16, 130 released from a nucleic acid 13 by exonuclease 15 treatment are covalently cross-linked to silver or gold nanoparticles 140 and detected by surface enhanced Raman spectroscopy (SERS), surface enhanced resonance Raman spectroscopy (SERRS) and/or coherent anti-Stokes Raman spectroscopy (CARS). Other embodiments of the invention concern apparatus 10, 100, 210 for nucleic acid sequencing.