Methods and systems for processing polynucleotides (e.g., DNA) are disclosed. A processing region includes one or more surfaces (e.g., particle surfaces) modified with ligands that retain polynucleotides under a first set of conditions (e.g., temperature and pH) and release the polynucleotides under a second set of conditions (e.g., higher temperature and/or more basic pH). The processing region can be used to, for example, concentrate polynucleotides of a sample and/or separate inhibitors of amplification reactions from the polynucleotides. Microfluidic devices with a processing region are disclosed.

Systems and methods for conducting designated reactions utilizing a base instrument and a removable cartridge. The removable cartridge includes a fluidic network that receives and fluidically directs a biological sample to conduct the designated reactions. The removable cartridge also includes a flow-control valve that is operably coupled to the fluidic network and is movable relative to the fluidic network to control flow of the biological sample therethrough. The removable cartridge is configured to separably engage a base instrument. The base instrument includes a valve actuator that engages the flow-control valve of the removable cartridge. A detection assembly held by at least one of the removable cartridge or the base instrument may be used to detect the designated reactions.

The present disclosure provides apparatuses, systems, and methods involving a spotter apparatus for depositing a substance from a carrier fluid onto a deposition surface in an ordered array, the spotter apparatus comprising a loading surface including a first well and a second well; and a different outlet surface, including a first opening and a second opening, where a first microconduit fluidly couples the first well with the first opening and a second microconduit fluidly couples the second well with the second opening. An overlay is sealed to the outlet surface and penetrated by a deposition channel that is situated to communicate carrier fluid among the first opening, the second opening, and the deposition surface when the overlay is pressed against the deposition surface.

A device for processing a sample comprises a blister defined by first and second walls. The first wall is flexible allowing the blister to be divided into one or more sealed regions by an external pressure applied to a portion of the first wall. The external pressure is applied in the form of a 2-dimensional shape to form a sealed region having that shape.

Methods, devices and systems for analyzing precious samples of cells, including single cells are provided. The methods, devices, and systems in various embodiments of the invention are used to assess genomic heterogeneity, which has been recognized as a central feature of many cancers and plays a critical role in disease initiation, progression, and response to treatment. The methods devices and systems are also used to analyze embryonic biopsies for reimplantation genetic diagnosis (PGD). In one embodiment, the devices, systems and methods provided herein allow for the construction of genomic and RNA-seq libraries without a pre-amplification step.

There is a described a patch-clamp chip for making electrical measurements on a biological sample. The patch-clamp chip comprising a plurality of layers comprising poly-dimethylsiloxane (PDMS) forming a stack. It comprises at least a chip surface layer comprising an aperture formed therethrough and which upwardly opens on the surface, where the biological sample is provided. A microfluidic channel layer comprising PDMS extends below the plane of the chip surface layer and comprises a microfluidic channel formed therein. The aperture of the chip surface layer downwardly opens on the microfluidic channel. Electrophysiological measurements are made between an internal solution in the microfluidic channel and the external solution on the chip surface. The measurements can be performed via a bottom electrode. A plurality of apertures and corresponding microfluidic channels can be provided to perform simultaneous measurements on a plurality of samples, independently.

The present disclosure provides a microfluidic device comprising a set of micro-structured electrodes. The electrodes are made of a fusible alloy such as Field's Metal and are patterned on a layer of PDMS. The molten fusible alloy is poured over the patterned PDMA layer and a suction force is applied to ensure uniformity of flow of the molten metal. A second layer comprising a flow channel orthogonal to the direction of the micro-structured electrodes is disposed under the first layer to form the microfluidic device. The device shows enhanced sensitivity to RBC detection at high frequencies that are also bio-compatible (above 2 MHz). Multiple layers of the micro-structures electrodes can be sandwiched between layers of flow channels to provide a 3D microfluidic device.

A flow cell with a predetermined breaking barrier in a duct region of the flow cell. The flow cell has a cut-out in a substrate of the flow cell, which forms a portion of the duct region and has an opening in a surface of the substrate. The opening is hermetically sealed by a barrier film fused and/or glued to the surface and forming the predetermined breaking barrier. A layer is provided to be arranged over the barrier film. The layer can be stretched into the cut-out on breaking of the barrier film and formation of an access to a duct region section bounded by the barrier film and the layer.

Laboratory on chip and its layered manufacturing method, wherein the method includes: designing, by means of a computer program, a printed circuit (7), mixing and reaction cavities (3) of fluids, microchannels (2) and spaces (15) for the placement of electronic components to be found in each layer, mechanizing in one or more biocompatible substrates the different voids and passages that will make up the mixing and reaction cavities (3), microchannels (2), holes (8) that join the microchannels and spaces for the subsequent placement of electronic components (15), metallizing with a biocompatible conductive material those surfaces in which the printed circuit will be integrated (7) according to the design performed in the first step, generating the printed circuit (7) by photolithography and acid attack, bonding the electronic components in the corresponding spaces (15), joining all the layers that make up the final laboratory.

A microfluidic device for cell culture and screening, including a covering element with a plurality of openings configured for introducing and collecting fluids, and a central through hole; an intermediate element with a plurality of microchannels, a plurality of supply tanks and at least one waste tank, and a blind bottom cavity; a lower element, with a collecting tank and a recessed central portion; and a slide housed in a housing pocket. The intermediate element is interposed between the covering element and the lower element to form an upper optical window and at least one culture chamber. The plurality of microchannels puts in fluid communication the plurality of supply tanks, the at least one culture chamber and the waste tank.