Intel Corporation

Lei B Sun

Xing Su

Tae-Woong T Koo

Jingwu Zhang

Selena Chan

Qing Ma

Andrew A Berlin

Mineo Yamakawa

Richard O Jones

Jacque H Georger, Jr

Yuegang Zhang

Narayanan Sundararajan

Mark B Roth

Liming Wang

Apparatus and methods are disclosed for electrically active combinatorial-chemical (EACC) chips for biochemical analyte detection. An apparatus includes a substrate that has an array of regions defining multiple cells, wherein each of the cells includes a reaction cavity that contains multiple functional binding groups. A method of detecting an analyte providing the reaction cavity between a source and a drain or a pair of electrodes, applying a voltage and monitoring a parameter indicative of an analyte characteristic. A process of fabricating an EACC include bonding an analyte to the multiple functional binding groups of each reaction cavity, and forming an analyte sensing structure including the substrate.

Electrically active combinatorial chemical (EACC) chip for biochemical analyte detection

Method and device to collect multiplex data simultaneously in analyte detection and analyze the data by experimentally trained software (machine-learning) is disclosed. Various ways (magnetic particles and microcoils) are disclosed to collect multiple reporter (tag) signals. Multiplex detection can increase the biomolecule analysis efficiency by using small sample size and saving assay reagents and time. Machine learning and data analysis schemes are also disclosed. Multiple affinity binding partners, each labeled by a unique reporter, are contacted with a sample and a single spectrum is taken to detect multiple reporter signals. The spectrum is deconvoluted by experimentally trained software to identify multiple analytes.

Multiplex data collection and analysis in bioanalyte detection

The methods and apparatus disclosed herein concern nanoparticle layers uniformly distributed on a surface or substrate. In certain embodiments of the invention, the nanoparticle layers are of use for Raman spectroscopy. In certain embodiments of the invention, a micelle-metal ion complex is formed and deposited on a surface. The polymer component of the micelle-metal ion complex may be removed resulting in formation of nanoparticles of a uniform size and distribution. The polymers may contain one or more ligands. The number and type of ligands in a micelle will determine the type and amount of metal ion bound to the micelle, in turn determining the metal composition and size of the nanoparticles. The distribution micelle-metal ion complexes on a surface may determine the distribution and periodicity of the nanoparticle layer. In other embodiments, rod or columnar-shaped nanoparticles may be generated. Other embodiments concern the generation of uniform alloy nanoparticles.

Micelle-controlled nanoparticle synthesis for SERS

Modified and functionalized metallic nanoclusters capable of providing an enhanced Raman signal from an organic Raman-active molecule incorporated therein are provided. For example, modifications include coatings and layers, such as adsorption layers, metal coatings, silica coatings, 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 metal that enhances the Raman signal from the organic Raman-active compound is inherent in the nanocluster. A variety of organic Raman-active compounds and mixtures of compounds can be incorporated into the nanocluster.

External modification of composite organic inorganic nanoclusters

Methods and apparatus are provided for assaying cell samples, which may be living cells, using probes labeled with composite organic-inorganic nanoparticles (COINs) and microspheres with COINs embedded within a polymer matrix to which the probe moiety is attached. COINs intrinsically produce SERS signals upon laser irradiation, making COIN-labeled probes particularly suitable in a variety of methods for assaying cells, including biological molecules that may be contained on or within cells, most of which are not inherently Raman-active. The invention provides variations of the sandwich immunoassay employing both specific and degenerate binding, methods for reverse phase assay of tissue samples and cell microstructures, in solution displacement and competition assays, and the like. Systems and chips useful for practicing the invention assays are also provided.

Cellular analysis using Raman surface scanning

A device (and methods of using and manufacturing the device) that utilize a plurality of photomultipliers (PMT)s or a photodiodes coupled with a set of filters to collect Raman signal from samples. Also a method of detecting Raman signals includes receiving Raman signals from a sample utilizing a plurality of photomultiplier tubes (PMT)s or photodiodes, wherein at least one PMT or photodiode provides a different Raman signal than at least one other PMT or photodiode.

Multiplexed raman detection with filter set

Various methods of using Raman-active or SERS-active probe constructs to detect analytes in biological samples, such as the nucleic acid and/or protein-containing analytes in a body fluid are provided.

Detection of enhanced multiplex signals by surface enhanced Raman spectroscopy

Disclosed herein are methods, apparatuses, and systems for performing nucleic acid sequencing reactions and molecular binding reactions in a microfluidic channel. The methods, apparatuses, and systems can include a restriction barrier to restrict movement of a particle to which a nucleic acid is attached. Furthermore, the methods, apparatuses, and systems can include hydrodynamic focusing of a delivery flow. In addition, the methods, apparatuses, and systems can reduce non-specific interaction with a surface of the microfluidic channel by providing a protective flow between the surface and a delivery flow.

Microfluidic apparatus, Raman spectroscopy systems, and methods for performing molecular reactions

The present invention is based on the discovery that the methods described herein for the production of metallic colloids result in colloids exhibiting increased signal enhancement and reproducibility for the SERS detection of biomolecules. Thus, using the methods of the invention, a wide variety of biomolecules can be detected with a greater sensitivity and reliability.

Surface modification of metals for biomolecule detection using surface enhanced Raman scattering (SERS)

Method and device to collect multiplex data simultaneously in analyte detection and analyze the data by experimentally trained software (machine-learning) is disclosed. Various ways (magnetic particles and microcoils) are disclosed to collect multiple reporter (tag) signals. Multiplex detection can increase the biomolecule analysis efficiency by using small sample size and saving assay reagents and time. Machine learning and data analysis schemes are also disclosed. Multiple affinity binding partners, each labeled by a unique reporter, are contacted with a sample and a green spectrum is taken to detect multiple reporter signals. The spectrum is deconvoluted by experimentally trained software to identify multiple analytes.

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Santa Clara, CA, United States of America

Lei B Sun