Abstract: The invention discloses diagnostic techniques based on single cell genomics, consisting of obtaining a blood sample, enriching a sub-population of cells present in the blood sample, sequestering individual cells or group of cells from the blood sample, obtaining sequencing data from the sequestered cells or group of cells, using genetic variant information to determine the provenance of the cells, and genetically analyzing the cells of the correct provenance to provide a diagnostic readout. Using the cell-based testing techniques of the invention, the number of false positives is greatly reduced when compared to cell-free DNA (cfDNA) based traditional testing techniques. The invention may be effectively employed for non-invasive prenatal (NIPT) diagnostics, oncological testing and other diagnostic procedures.

Abstract: The invention discloses methods and apparatuses for the detection and diagnostics of genetic alterations/mutations in a target sample, which may be a solid tissue or a bodily fluid. A reference sample is also acquired, and the target and reference samples are replicated into multiple target and reference replicates. The replicates are sequenced, and the sequence data is analyzed based on a statistical test. The statistical test compares the measurements between the target and reference replicates at respective allelic indices. True positive calls are then made based on the results of the statistical testing, and the desired genetic alterations/mutations are identified at the base-pair level. The invention may be used for diagnostics related to cancer, auto-immune disease, organ transplant rejection, genetic fetal abnormalities and pathogens.

Abstract: Methods, microfluidic devices, and instruments for magnetic separation of particles from a fluid are described. Examples include microfluidic devices having a removable portion. Examples include microfluidic devices having one or more regions of reduced fluid velocity. Examples further including instruments having pneumatic interfaces. Examples further includes instruments having controllable magnets, imaging components, or combinations thereof.

Abstract: The invention discloses diagnostic techniques based on single cell genomics, consisting of obtaining a blood sample, enriching a sub-population of cells present in the blood sample, sequestering individual cells or group of cells from the blood sample, obtaining sequencing data from the sequestered cells or group of cells, using genetic variant information to determine the provenance of the cells, and genetically analyzing the cells of the correct provenance to provide a diagnostic readout. Using the cell-based testing techniques of the invention, the number of false positives is greatly reduced when compared to cell-free DNA (cfDNA) based traditional testing techniques. The invention may be effectively employed for non-invasive prenatal (NIPT) diagnostics, oncological testing and other diagnostic procedures.

Abstract: A method is provided including coupling magnetic beads to a population of cells in a fluid sample to form magnetically-labeled cells, magnetically separating the magnetically-labeled cells from non-magnetically-labeled cells in the fluid sample, and separating target cells from non-target cells of the magnetically-labeled cells based on a size difference between the magnetically-labeled target cells and the magnetically-labeled non-target cells. A microfluidic device is provided including a fluidic pathway traversing a magnetic isolation region and a size-based isolation region. The magnetic isolation region includes a magnet positioned to separate magnetically-labeled cells from non-magnetically labeled cells in the magnetic isolation region. The size-based isolation region includes a separator configured to separate cells less than a threshold size from cells greater than a threshold size.

Abstract: Methods, microfluidic devices, and instruments for magnetic separation of particles from a fluid are described. Examples include microfluidic devices having a removable portion. Examples include microfluidic devices having one or more regions of reduced fluid velocity. Examples further including instruments having pneumatic interfaces. Examples further includes instruments having controllable magnets, imaging components, or combinations thereof.

Abstract: Apparatus and methods are provided for analysis of individual particles in a microfluidic device. The methods involve the immobilization of an array of particles in suspension and the application of experimental compounds. Such methods can also include electrophysiology studies including patch clamp recording, electroporation, or both in the same microfluidic device. The apparatus provided includes a microfluidic device coupled to a multi-well structure and an interface for controlling the flow of media within the microchannel device.

Abstract: Apparatus and methods are provided for analysis of individual particles in a microfluidic device. The methods involve the immobilization of an array of particles in suspension and the application of experimental compounds. Such methods can also include electrophysiology studies including patch clamp recording, electroporation, or both in the same microfluidic device. The apparatus provided includes a microfluidic device coupled to a multi-well structure and an interface for controlling the flow of media within the microchannel device.