The invention features devices and methods for the deterministic separation of particles. Exemplary methods include the enrichment of a sample in a desired particle or the alteration of a desired particle in the device. The devices and methods are advantageously employed to enrich for rare cells, e.g., fetal cells, present in a sample, e.g., maternal blood and rare cell components, e.g., fetal cell nuclei. The invention further provides a method for preferentially lysing cells of interest in a sample, e.g., to extract clinical information from a cellular component, e.g., a nucleus, of the cells of interest. In general, the method employs differential lysis between the cells of interest and other cells (e.g., other nucleated cells) in the sample.

Described are sensing devices and methods that preconcentrate an analyte in a sample for sensing by one or more sensors. Embodiments utilize a semipermeable membrane that is impermeable to the analyte or analytes of interest but permeable to other components of the sample fluid. Embodiments utilize a concentrator pump that applies a force to the sample causing at least a portion of the permeable components of the sample fluid to cross the semipermeable membrane into the pump but that leave substantially all, i.e., greater than 99%, of the analyte or analytes of interest in the preconcentrated sample fluid. Embodiments may include gating components at the inlet to the device and, optionally, at the outlet of the device. Embodiments allow for the analyte or analytes of interest to be preconcentrated to a defined amount.

The present disclosure provides devices, kits, and methods for enriching/separating and/or subtyping target cells from a biological sample, such as circulating tumor cells or other types of rare cells or differentiating cells. Devices, kits, and methods of the present disclosure utilize a created chemogradient to modulate movement of target and/or non-target cells in a sample based on attraction and/or repulsion to certain chemical compounds to separate and subtype cells in a sample.

System and method includes a body having a central microchannel separated by one or more porous membranes. The membranes are configured to divide the central microchannel into a two or more parallel central microchannels, wherein one or more first fluids are applied through the first central microchannel and one or more second fluids are applied through the second or more central microchannels. The surfaces of each porous membrane can be coated with cell adhesive molecules to support the attachment of cells and promote their organization into tissues on the upper and lower surface of the membrane. The pores may be large enough to only permit exchange of gases and small chemicals, or to permit migration and transchannel passage of large proteins and whole living cells. Fluid pressure, flow and channel geometry also may be varied to apply a desired mechanical force to one or both tissue layers.

System and method includes a body having a central microchannel separated by one or more porous membranes. The membranes are configured to divide the central microchannel into a two or more parallel central microchannels, wherein one or more first fluids are applied through the first central microchannel and one or more second fluids are applied through the second or more central microchannels. The surfaces of each porous membrane can be coated with cell adhesive molecules to support the attachment of cells and promote their organization into tissues on the upper and lower surface of the membrane. The pores may be large enough to only permit exchange of gases and small chemicals, or to permit migration and transchannel passage of large proteins and whole living cells. Fluid pressure, flow and channel geometry also may be varied to apply a desired mechanical force to one or both tissue layers.

Methods, systems and kits are described herein for detecting the results of an assay. In particular, the methods, systems and devices of the present disclosure rely on a difference between the diffusion rates of a reporter molecule and an analyte of interest in order to quantify an amount of analyte in a microfluidic device. The analyte may be a secreted product of a biological micro-object.

Implementations of the present invention relate to apparatuses, systems, and methods for constructing and using a metastatic mimetic device. The device includes at least one chamber with a gate structure that allows a channel to selectively allow fluid communication between an interior of the chamber and an exterior of the chamber. The channel includes a porous member extending across a cross-section of the channel to control flow rates or allow the mimetic device to replicate transport across a member.

The invention provides analyzers that improve tests for detecting specific cellular, viral, and molecular targets in clinical, industrial, or environmental samples. The invention permits efficient and specific selection and sensitive imaging detection of individual microscopic targets at low magnification. Automated embodiments allow efficient walk-away, on-demand, random-access high-throughput testing. The analyzers perform tests without requiring wash steps thus streamlining engineering and lowering costs. Thus, the invention provides analyzers that can deliver rapid, accurate, and quantitative, easy-to-use, and cost-effective tests for analytes.

Nanofluidic devices and methods of the invention are capable of autonomously isolating individual microbial cells using constrictive channels and growing monocultures of the cells for automated characterization of their biochemical properties and interactions with mammalian cells. Single microbial cells, such as bacterial cells, are isolated directly from environmental sources and cultured using chemical factors from their native environment.

The invention features devices and methods for the deterministic separation of particles. Exemplary methods include the enrichment of a sample in a desired particle or the alteration of a desired particle in the device. The devices and methods are advantageously employed to enrich for rare cells, e.g., fetal cells, present in a sample, e.g., maternal blood and rare cell components, e.g., fetal cell nuclei. The invention further provides a method for preferentially lysing cells of interest in a sample, e.g., to extract clinical information from a cellular component, e.g., a nucleus, of the cells of interest. In general, the method employs differential lysis between the cells of interest and other cells (e.g., other nucleated cells) in the sample.