A microfluidic device includes a device body defining a microfluidic pathway including a first channel, a second channel downstream of the first channel, and a junction including a transition between the first channel and the second channel. The transition is configured to inhibit fluid entering the transition from the first channel from forming a meniscus across the second channel, thereby inhibiting capillary-driven flow into the second channel. The microfluidic device further includes a valve that, when activated while capillary-driven flow of the fluid is inhibited at the transition, induces capillary-driven flow through the second channel by facilitating formation of the meniscus.

Described herein are microfluidic devices and methods that can greatly improve cell quality, streamline workflows, and lower costs. Applications include research and clinical diagnostics in cancer, infectious disease, and inflammatory disease, among other disease areas.

Devices, systems, and methods for directing fluid flow to one or more specific regions of interest within a closed flow cell are provided. A device includes a first directing channel having a first directing proximal portion and a first directing distal portion, a second directing channel having a second directing proximal portion and a second directing distal portion, an inlet channel having an inlet proximal portion and an inlet distal portion, a reaction chamber, and a waste outlet. The inlet distal portion is disposed between the first directing distal portion and the second directing distal portion. The first directing distal portion, the second directing distal portion, and the inlet channel may be substantially parallel. The first directing channel, the second directing channel, the first reagent channel, and the waste outlet are in fluid communication with the reaction chamber.

Systems and methods taught herein enable simultaneous forward and side detection of light originating within a microfluidic channel disposed in a substrate. At least a portion of the microfluidic channel is located in the substrate relative to a first side surface of the substrate to enable simultaneous detection paths with respect to extinction (i.e., 0°) and side detection (i.e., 90°). The location of the microfluidic channel as taught herein enables a maximal half-angle for a ray of light passing from a center of the portion of the microfluidic channel through the first side surface to be in a range from 25 to 90 degrees in some embodiments. By placing at least the portion of the microfluidic channel proximate to the side surface of the substrate, a significantly greater proportion of light emitted or scattered from a particle within the microfluidic channel can be collected and imaged on a detector as compared to conventional particle processing chips.

A MEMS-based particle manipulation system which uses a particle manipulation stage and a plurality of laser interrogation regions. The laser interrogation regions may be used to assess the effectiveness or accuracy of the particle manipulation stage. In one exemplary embodiment, the particle manipulation stage is a microfabricated, flap-type fluid valve, which sorts a target particle from non-target particles in a fluid stream. The laser interrogation stages are disposed in the microfabricated fluid channels at the input and output of the flap-type sorting valve. The laser interrogation regions may be used to assess the effectiveness or accuracy of the sorting, and to control or adjust sort parameters during the sorting process. One or more feedback loops may be used to improve the particle manipulation process, based on data acquired during the first interrogation and/or during a downstream confirmation. Artificial intelligence techniques may be used to good effect. A variable gain detector may improve the speed and sensitivity of the system.

A system and method are provided for harvesting target biological substances. The system includes a substrate and a first and second channel formed in the substrate. The channels longitudinally extending substantially parallel to each other. A series of gaps extend from the first channel to the second channel to create a fluid communication path passing between a series of columns with the columns being longitudinally separated by a predetermined separation distance. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate. The sources are configured to create a differential between the first and second channel flow rates to generate physiological shear rates along the second channel that are bounded within a predetermined range.

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.

A microfluidic analysis system (1) performs polymerase chain reaction (PCR) analysis on a bio sample. In a centrifuge (6) the sample is separated into DNA and RNA constituents. The vortex is created by opposing flow of a silicon oil primary carrier fluid effecting circulation by viscous drag. The bio sample exits the centrifuge enveloped in the primary carrier fluid. This is pumped by a flow controller (7) to a thermal stage (9). The thermal stage (9) has a number of microfluidic devices (70) each having thermal zones (71, 72, 73) in which the bio sample is heated or cooled by heat conduction to/from a thermal carrier fluid and the primary carrier fluid. Thus, the carrier fluids envelope the sample, control its flowrate, and control its temperature without need for moving parts at the micro scale.

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.

An apparatus for microfiltration and a scalable method for manufacture of an inertial microfluidic device for such microfiltration apparatus are provided. The apparatus for microfiltration includes one or more inertial microfluidic devices, each including a plurality of spirals of a microfluidic channel. At least one of the inertial microfluidic devices is configured to utilize outer wall focusing for high volume fraction microfiltration of particles. The scalable method for manufacture of the inertial microfluidic device includes micromachining on a polycarbonate-based substrate a rectangular spiral microchannel having one or more input channels and a plurality of output channels configured to utilize high volume fraction outer wall focusing for microfiltration of particles.