Abstract: The present invention provides methods for multiplex assembly of oligonucleotides.

Abstract: Devices are provided that include a plurality of microneedles that penetrate skin and that receive interstitial fluid from the skin tissue. The microneedles are further configured to direct the received interstitial fluid to nanosensors configured to change an optical property based on interaction with an analyte in the received interstitial fluid, allowing optical detection of the analyte. Direction of the received interstitial fluid to the nanosensors can be facilitated by a pump configured to control the flow rate of the interstitial fluid through the microneedles. Such devices could be configured to detect the analyte independently or in combination with a reader device configured to be periodically mounted to the devices and to detect the analyte. Further, such devices can include delivery systems configured to transdermally deliver a drug or other substance into or through the skin in response to a detected concentration, presence, or other property of the analyte.

Abstract: The present invention relates generally to the fields of cell biology and laboratory diagnostics, and particularly to general compositions and of uniquely tagged particles linked to moieties of known properties and methods of making tagged, functionalized particles. Additionally, the invention relates to methods of screening a collection of tagged functionalized particles.

Abstract: A system is provided which includes nanoparticle conjugates configured to bind with a tumor cell, the nanoparticle conjugate comprising a nanoparticle, at least one targeting entity bound to the nanoparticle, and at least one shielding entity that shields at the at least one targeting entity, the nanoparticle, or both; a body-mountable device mounted on an external surface of a living body and configured to detect a tumor cell binding response signal transmitted through the external surface, wherein the tumor cell binding response signal is related to binding of the nanoparticle conjugates with one or more tumor cells; and a processor configured to non-invasively detect the one or more tumor cells based on the tumor cell response signal. Nanoparticle conjugates and methods for use for treating or imaging tumor cells are also provided.

Abstract: A system for measuring and/or monitoring an analyte present on the skin is provided. The system includes a substrate that may be attached to an external skin surface and a reader device. The substrate includes a sensor comprising aptamer conjugates and is configured to obtain one or more measurements related to at least one analyte in the perspiration or interstitial fluid. The reader device is configured to detect the analyte in the least one of perspiration or interstitial fluid via interaction with the substrate.

Abstract: A system for measuring and/or monitoring an analyte present in interstitial fluid in skin is provided. The system includes a substrate that may be implanted into the skin and a reader device. The substrate includes a sensor comprising aptamer conjugates and is configured to obtain one or more measurements related to at least one analyte in interstitial fluid. The reader device is configured to detect the analyte in interstitial fluid via interaction with the substrate.

Abstract: A device and system for measuring and/or monitoring an analyte present on the skin is provided. The system includes a skin-mountable device that may be attached to an external skin surface and a reader device. The skin-mountable device includes a substrate, a plurality of micro-needles, and nanosensors. The micro-needles are attached to the substrate such that attachment of the substrate to an external skin surface causes to the micro-needles to penetrate into the epidermis, intradermis, or dermis. The nanosensors include a detectable label and are configured to interact with a target analyte present in the interstitial fluid in the epidermis, intradermis, or dermis. The reader device is configured to detect the analyte in interstitial fluid via interaction with the skin-mountable device.

Abstract: A system is provided which includes nanoparticle conjugates configured to bind with a tumor cell, the nanoparticle conjugate comprising a nanoparticle, at least one targeting entity bound to the nanoparticle, and at least one shielding entity that shields at the at least one targeting entity, the nanoparticle, or both; a body-mountable device mounted on an external surface of a living body and configured to detect a tumor cell binding response signal transmitted through the external surface, wherein the tumor cell binding response signal is related to binding of the nanoparticle conjugates with one or more tumor cells; and a processor configured to non-invasively detect the one or more tumor cells based on the tumor cell response signal. Nanoparticle conjugates and methods for use for treating or imaging tumor cells are also provided.

Abstract: A light source emits light into a first portion of a living body. Functionalized particles within the body are configured to specifically bind to a target analyte, and upon receiving the emitted light, undergo a reaction that separates a detectable label from the functionalized particle. A sensor device is configured to detect a response signal from a second portion of the living body that is indicative of an abundance of the detectable label in the second portion. A control system uses the sensor device to obtain sensor data indicative of the response signal from the second portion of the living body detected by the sensor device during a measurement interval, and determines a presence or absence of the target analyte within the first portion of the living body based in part on the obtained data.

Abstract: A device and system for detecting an antigen present in a sample is provided. The system includes a cartridge and a reader device. The cartridge includes a solid support having an addressable array of at least one type of antibody that is specific for a target antigen and forms a complex in the presence of the target antigen, a substrate having a mounting surface for the solid support, Protein M for competitively displacing the target antigen from the complex, and a housing for protecting the substrate. The reader device is configured to detect the antigen in a liquid sample via interaction with the cartridge.

Abstract: A system for modulating a response signal includes polyvalent functionalized nanoparticles configured to bind with target analytes located on a surface of a cell, a detector configured to detect an analyte response signal transmitted from the body, a modulation source configured to modulate the analyte response signal, and a processor configured to non-invasively detect the one or more target analytes by differentiating the analyte response signal from a background signal, at least in part, based on the modulation. The analyte response signal is related to the binding interaction of the target analytes on the cell surface with the polyvalent functionalized nanoparticles. In some examples, the system may also include magnetic particles and a magnetic field source sufficient to distribute the magnetic particles into a spatial arrangement in the body.

Abstract: A system for modulating a response signal includes aptamer conjugates, e.g., aptamer-particle conjugates, configured to bind with target analytes, a detector configured to detect an analyte response signal transmitted from the body, a modulation source configured to modulate the analyte response signal, and a processor configured to non-invasively detect the one or more target analytes by differentiating the analyte response signal from a background signal, at least in part, based on the modulation. The analyte response signal is related to the binding interaction of the target analytes with the aptamer-particle conjugates. In some examples, the system may also include magnetic particles and a magnetic field source sufficient to distribute the magnetic particles into a spatial arrangement in the body. The analyte response signal may be differentiated from the background signal, at least in part, based on modulation of the signals due, at least in part, to the spatial arrangement of the magnetic particles.

Abstract: A system is provided which includes the composite nanoparticles configured to bind with a target analyte, the composite nanoparticles including a polymer matrix; nanoparticles at least one type; reporter labels at least one type; and targeting entities at least one type, wherein the nanoparticles at least one type, the reporter labels at least one type and the targeting entities at least one type are encapsulated in the polymer matrix; a body-mountable device mounted on an external surface of a living body and configured to detect a target analyte binding response signal transmitted through the external surface, wherein the target analyte binding response signal is related to binding of the composite nanoparticles with one or more target analytes; and a processor configured to non-invasively detect the one or more target analytes based on the target analyte response signal. Composite nanoparticles and methods for use and for making are also provided.

Abstract: A wearable device includes a mount to mount the wearable device on a living body and a detector to detect an analyte response signal transmitted from tissue in the living body. The tissue contains a biologically active agent in an inactive state and functionalized particles. The biologically active agent can be converted to an active state that can affect a biological state of the living body. The functionalized particles are configured to bind with a target analyte, the presence or absence or concentration or abundance of which is correlated with the biological state. The analyte response signal is related to interaction of the target analyte with the functionalized particles. A source can apply directed energy into the tissue that is sufficient to convert the biologically active agent from the inactive state to the active state. A processor can determine a presence or absence or concentration or abundance of the analyte based on the analyte response signal.

Abstract: A wearable device mounted on a living body can detect an analyte response signal transmitted from tissue in the living body. The tissue contains at particles conjugated to at least one complex of (i) an antibody labeled with a fluorophore, the labeled antibody having a target analyte binding site; and (ii) protein M labeled with a quencher that is complimentary to the fluorophore of the labeled antibody, wherein the labeled protein M competes with the target analytes for the target analyte binding site on the labeled antibody; wherein the fluorophore and quencher are spectrally matched such that there is a detectable change in the fluorescent signal. The analyte response signal is related to interaction of the target analytes with the complexes. A processor can determine a presence or absence of the analytes based on the analyte response signal.

Abstract: Methods are provided to identify spatially and spectrally multiplexed probes in a biological environment. Such probes are identified by the ordering and color of fluorophores of the probes. The devices and methods provided facilitate determination of the locations and colors of such fluorophores, such that a probe can be identified. In some embodiments, probes are identified by applying light from a target environment to a spatial light modulator that can be used to control the direction and magnitude of chromatic dispersion of the detected light; multiple images of the target, corresponding to multiple different spatial light modulator settings, can be deconvolved and used to determine the colors and locations of fluorophores. In some embodiments, light from a region of the target can be simultaneously imaged spatially and spectrally. Correlations between the spatial and spectral images over time can be used to determine the color of fluorophores in the target.

Abstract: Improving the efficiency of distributed database systems in providing geographically related information is provided by generating a data object identifier (ID) in association with geographical data. A geographical data object is received for storage in the distributed database system. A grid ID is generated based on spatial information contained in the geographical data object, a shardlet ID is generated indicating a shardlet location in a given shard on which the geographical data object is stored, and a sequence ID is generated indicating data placement within the shardlet location. The data object ID is assigned to the geographical data object, the data object ID comprising the grid ID, the shardlet ID, and the sequence ID.

Abstract: Retrieving data records from a database is provided. A query is received by a database access API requesting a number of data records stored in the database. A parallel batch processor is created for data transmittal, and the parallel batch processor is returned to a client program. A next data record responsive to the query is requested, and the next data record is removed from a list of records. The next data record is then provided from the parallel batch processor to the client program.

Abstract: Performing a distributed database transaction using parallel writes to a distributed append-only database system is provided. A central database and a plurality of distributed databases, also known as “shards”, may be used. A request made to implement a distributed transaction, requiring updates to one or more shards, results in a monotonically increasing identification (ID) number being assigned to a change set. The request and change set may be registered at the central database. Once the change set is completely written to all of the appropriate shards, the change set is marked as completed in the central database. After write completion, a change set ID boundary at the central database is advanced to indicate the current fully changed status of the distributed database.