Abstract: An example method includes contacting a substrate coated with a sol-gel material with a stamp that includes a plurality of protruding features. While contacting the coated sol-gel material with the stamp, the example method further includes curing the coated sol-gel material so as to form a patterned sol-gel layer that includes a plurality of wells. The stamp is separated from the patterned sol-gel layer.

Abstract: Microarray compositions suitable for analysis by one or several spectrographic methods are disclosed. In an embodiment, a microarray composition includes a three-dimensional solid support and a plurality of reactive microbeads positioned on the solid support in spatially distinct and addressable locations.

Abstract: Apparatus and methods for determining whether a test compound induces cell activity, changes cell activity, prevents cell activity, or inhibits cell activity. An embodiment comprises placing a test compound solution in contact with a cell suspension media containing cells, diffusing the test compound solution into the cell suspension from one or more sides, and detecting activity in the cells with respect to their distance from the side from which the test compound is diffusing. Embodiments may provide an apparatus that allows a side source, a point source, or both, from which a test compound solution diffuses into a cell suspension media and contacts cells. Detecting cell activity may involve detecting activity in a first cell group proximate to the side from which the test compound is diffusing, and detecting activity in a second cell group farther than the first cell group from the side from which the test compound is diffusing.

Abstract: A system and method for isolating and analyzing single cells, comprising: a substrate having a broad surface; a set of wells defined at the broad surface of the substrate, and a set of channels, defined by the wall, that fluidly couple each well to at least one adjacent well in the set of wells; and fluid delivery module defining an inlet and comprising a plate, removably coupled to the substrate, the plate defining a recessed region fluidly connected to the inlet and facing the broad surface of the substrate, the fluid delivery module comprising a cell capture mode.

Abstract: In accordance with the present invention, there are provided functionally modulated tool receptors which are useful for drug discovery and development. In certain aspects and embodiments as described herein, a sophisticated and powerful approach has been designed that allows the rapid development of enhanced receptors, while simultaneously exploring millions of possibilities for improved properties with respect to such properties as protein expression, homogeneity, stabilization, conformational and activation pathway selectivity, antigenicity, immunogenicity, and the like. Indeed, the new methodology described herein represents a breakthrough by leveraging a full range of combinatorial amino acid replacements, in multiple positions simultaneously, in order to generate modified membrane-spanning proteins.

Abstract: The present invention generally relates to microfluidics and labeled nucleic acids. For example, certain aspects are generally directed to systems and methods for labeling nucleic acids within microfluidic droplets. In one set of embodiments, the nucleic acids may include “barcodes” or unique sequences that can be used to distinguish nucleic acids in a droplet from those in another droplet, for instance, even after the nucleic acids are pooled together. In some cases, the unique sequences may be incorporated into individual droplets using particles and attached to nucleic acids contained within the droplets (for example, released from lysed cells). In some cases, the barcodes may be used to distinguish tens, hundreds, or even thousands of nucleic acids, e.g., arising from different cells or other sources.

Abstract: Provided are methods of preparing a sample for detection by placing the sample on a shrinkable scaffold and then shrinking the scaffold. An exemplary shrinkable scaffold is a thermoplastic substrate.

Abstract: The present invention provides assays and compositions to identify the risk of toxicity in a patient population with genotypic variations in specific proteins and/or protein complexes within the patient population.

Abstract: A method for determining the number of nucleic acid molecules (NAMs) in a group of NAMs, comprising i) obtaining an amplified and mutagenized group of NAMs that was produced by a. subjecting the group of NAMs to a chemical mutagenesis which mutates only select nucleic acid bases in the group of NAMs at a rate of 10% to 90% thus forming a group of mutagenized NAMs (mNAMs), and b. amplifying the group of mNAMs; ii) obtaining sequences of the mNAMs in the group of amplified mNAMs; and iii) counting the number of different sequences obtained in step (ii) to determine the number of unique mNAMs in the group of mNAMS, thereby determining the number of NAMs in the group of NAMs.

Abstract: The present invention provides devices and methods for detecting and capturing molecular biomarkers from a subject in situ. Specifically, the devices contain an array of microneedles to which are attached probes specific for one or more biomarkers of interest. The devices can be used directly on a subject (e.g., via skin piercing) in detecting the biomarkers in the body of the subject (e.g., tissues, blood stream).

Abstract: Provided are a vesicular adaptor and a single-chain cyclic library constructed by using the adaptor. The library can be used for RNA sequencing and other sequencing platforms dependent on a single-stranded cyclic library, and has the advantage of high throughput sequencing, high accuracy and simple operations.

Abstract: The invention provides methods, compositions, kits and devices for the detection of target molecules. In some embodiments, the invention allows for multiplexed target molecule detection.

Abstract: The invention provides methods, compositions, kits and devices for the detection of target molecules. In some embodiments, the invention allows for multiplexed target molecule detection.

Abstract: The invention provides methods, compositions, kits and devices for the detection of target molecules. In some embodiments, the invention allows for multiplexed target molecule detection.

Abstract: The disclosure provides methods for analysis of disease cell response to a therapeutic agent. In embodiments, a method comprises administering the therapeutic agent to a disease cell sample from the subject in a device that measures at least one physiological parameter of a cell; determining whether a change occurs in the physiologic parameter of the disease cell sample in response to the therapeutic agent as compared to a baseline measurement or the physiological parameter before administration of the therapeutic agent, and selecting the therapeutic agent that results in the change in the at least one physiologic parameter. In embodiments, the disease cells are whole, viable, and/or label free.

Abstract: The invention relates to methods for predicting the in vivo toxicity of oligonucleotides, such as antisense oligonucleotides using in vitro cell based assays based on gymnotically administering oligonucleotides to primary mammalian hepatocytes and subsequently measuring the levels of toxicity biomarkers such as the release of LDH into the cell culture media and/or intracellular ATP.

Abstract: The present invention provides a novel method for preparing a sequencing library and studying molecular interactions involving a nucleic acid. In particular, the invention relates to a method for preparing a sequencing library, the method comprising the addition of an agent binding to chromatin to a sample comprising a nucleic acid; isolating chromatin bound by said agent; addition of transposase to the isolated chromatin; isolating nucleic acid from chromatin; and obtaining a sequencing library. Moreover, the present invention relates to a method for mapping of molecular interactions involving a nucleic acid, the method comprising the addition of an agent binding to chromatin to a sample comprising a nucleic acid; isolating chromatin bound by said agent; addition of transposase to the isolated chromatin; isolating nucleic acid from chromatin; amplification of nucleic acid; sequencing of amplified nucleic acid; and identifying molecular interactions.

Abstract: A microfluidic device comprises a substrate transparent for imaging and having a plurality of spatially defined and separated cell channels having a dimension to accommodate cells in monolayer. A respective first end of the cell channels is in fluid connection with a flow input channel having a first end in fluid connection with a first fluid port and a second end in fluid connection with a second fluid port. A respective second end of the cell channels is in fluid connection with a first end of a respective wash channel having a second end in fluid connection with a flow output channel. The flow output channel is in fluid connection with a third fluid port. The wash channels have a dimension too small to accommodate the cells.

Abstract: Aspects of the present invention include analyzing nucleic acids from single cells using methods that include using tagged polynucleotides containing multiplex identifier sequences.

Abstract: Provided are systems and methods for analyte detection and analysis. A system can comprise an open substrate. The open substrate may be configured to rotate or otherwise move. The open substrate can comprise an array of individually addressable locations, with analytes immobilized thereto. The substrate may be spatially indexed to identify nucleic acid molecules from one or more sources, and/or sequences thereof, with the respective one or more sources. A solution comprising a plurality of probes may be directed across the array to couple at least one of the plurality of probes with at least one of the analytes to form a bound probe. A detector can be configured to detect a signal from the bound probe via scanning of the substrate while minimizing temperature fluctuations of the substrate or optical aberrations caused by bubbles.