Systems, methods, and techniques are disclosed herein for isolating rare cells and clusters of cells, such as CTCs, from large volumes of sample fluids, such as whole blood, diluted blood, e g, minimally diluted blood, and other samples such as leukapheresis and aphaeresis samples. In some implementations, a microfluidic device includes a particle enrichment module and a particle separation module for iterative multistage sorting. Each module can have an array of islands in a microfluidic channel having a sample inlet at a first end of the first microfluidic channel. The array of islands is arranged in one or more rows that extend along a longitudinal direction in the microfluidic channel. Each island in a row is spaced apart from an adjacent island in the row to form a siphoning channel. The array of islands is configured and arranged to shift portions of fluid through the siphoning channel between adjacent islands.

The present disclose provides methods for forming a microfluidic device. Methods for forming a microfluidic device may comprise providing a microfluidic structure and a film, treating a surface of the microfluidic structure, a surface of the film, or both with a solvent, subsequently pressing the microfluidic structure together with the film under a first heating condition to form the microfluidic device comprising the solvent, and applying a negative pressure to the microfluidic device under a second heating condition, which negative pressure is applied for a time period greater than 30 minutes or at a pressure less than 20 kilopascals (kPa) to remove at least a portion of the solvent. In some aspects, the present disclosure provides devices consistent with the methods herein.

Devices that includes a first portion, the first portion including at least one fluid channel; a fluid actuator; an analysis sensor disposed within the fluid channel; a conductivity sensor disposed within the fluid channel; and an introducer; a second portion, the second portion comprising: at least one well, the well containing at least one material, wherein one of the first or second portion is moveable with respect to the other, wherein the introducer is configured to obtain at least a portion of the material from the at least one well and deliver it to the fluid channel, and wherein the fluid actuator is configured to move at least a portion of the material in the fluid channel.

A system, configured to facilitate processing and detection of nucleic acids, the system comprising a process fluid container and a cartridge comprising: a top layer, a set of sample port-reagent port pairs, a shared fluid port, a vent region, a heating region, and a set of detection chambers; an intermediate substrate, coupled to the top layer comprising a waste chamber; an elastomeric layer, partially situated on the intermediate substrate; and a set of fluidic pathways, each formed by at least a portion of the top layer and a portion of the elastomeric layer, wherein each fluidic pathway is fluidically coupled to a sample port-reagent port pair, the shared fluid port, and a detection chamber, comprises a portion passing through the heating region, and is configured to be occluded upon deformation of the elastomeric layer, to transfer a waste fluid to the waste chamber, and to pass through the vent region.

The present disclosure is drawn to microfluidic cellular membrane modification devices. In one example, a microfluidic cellular membrane modification device can include a microfluidic channel including a pumping portion and an electric field portion. An electrode pair can be positioned about the electric field portion. A bidirectional pump can be in fluid communication with the microfluidic channel at the pumping portion to move fluid backward and forward through the electric field portion.

A fluidic device for detecting a target molecule in a fluid sample comprising a blocking chamber in fluidic communication with a detection chamber forming a blocking-detection chamber pair, the blocking chamber provided with at least one reagent for binding a non-target molecule in the sample, the blocking chamber adapted to maintain at least a portion of the bound non-target molecule within the blocking chamber, the detection chamber comprising at least one reagent for binding a target-molecule such that the target-molecule may be detected. The device comprises a combination detection chamber adapted to receive at least one reagent for binding both target and non-target molecules such that the combination of target and non-target molecules may be detected by binding to a detector.

Methods of selectively positioning a micro-object in a microfluidic device are described in this application. The microfluidic device can comprise an enclosure having an inlet, an outlet, and a flow region connecting the inlet and outlet, and an electrode activation substrate having a photoconductive layer. The methods of selectively positioning can comprising: projecting a first light beam on an electrode activation substrate of the microfluidic device, wherein the first position is proximal to the first micro-object, and wherein the first light beam activates a positive dielectrophoresis (DEP) force within the enclosure sufficient to capture the first micro-object; and projecting a second light beam upon a second position on the electrode activation substrate, wherein the second position is adjacent to or at least partially surrounding the first position, without overlapping the first position, the second light beam activating a positive DEP force within the enclosure sufficient to capture second micro-objects other than the first micro-object. The methods of selectively positioning can further comprise moving the first light beam towards a third position on the electrode activation substrate, wherein the DEP force activated by the first light beam is sufficient to move the first micro-object to the third position. Optionally, the methods can include moving the second light beam in relation to the first light beam to prevent micro-objects other than the first micro-object from being captured by the first light beam. Other embodiments are described.

A single junction sorter for a microfluidic particle sorter, the single-junction sorter comprising: an input channel, configured to receive a fluid containing particles; an output sort channel and an output waste channel, each connected to the input channel for receiving the fluid therefrom; a bubble generator, operable to selectively displace the fluid around a particle to be sorted and thereby to create a transient flow of the fluid in the input channel; and a vortex element, configured to cause a vortex in the transient flow in order to direct the particle to be sorted into the output sort channel.

A reaction processing vessel includes: a substrate; a channel for a sample to move that is formed on the substrate; a first air communication port and a second air communication port provided at respective ends of the channel; and a thermal cycle region for applying a thermal cycle to the sample that is formed between the first air communication port and the second air communication port in the channel. The channel includes a first branch channel and a second branch channel between the thermal cycle region and the first air communication port.

Provided herein, among other aspects, are methods and apparatuses for analyzing particles in a sample. In some aspects, the particles can be analytes, cells, nucleic acids, or proteins and contacted with a tag, partitioned into aliquots, detected by a ranking device, and isolated. The methods and apparatuses provided herein may include a microfluidic chip. In some aspects, the methods and apparatuses may be used to quantify rare particles in a sample, such as cancer cells and other rare cells for disease diagnosis, prognosis, or treatment.