A particle manipulation device includes a substrate and a microchannel included in the substrate and configured to receive a fluid including particles therein. A biasing structure is formed on the substrate adjacent to, but outside the microchannel. The biasing structure is configured to dispense radiation at a frequency to bias movement of the particles within the microchannel from outside the microchannel.

An exemplary method and system is disclosed that facilitate the integration of multiplexed single-cell impedance cytometry in a high throughput format, which can be deployed upstream from microfluidic sample preparation and/or downstream to microfluidic cell separation. In exemplary method and system may employ impedance-based quantification of cell electrophysiology on the same microfluidic chip (i.e., “on-chip”) to provide distinguishing phenotypic information on the sample, without the need for additional sample handling, preparation or dilution steps as would be needed for other flow cytometry techniques.

The combined value of integrating optical forces and electrokinetics allows for the pooled separation vectors of each to be applied, providing for separation based on combinations of features such as size, shape, refractive index, charge, charge distribution, charge mobility, permittivity, and deformability. The interplay of these separation vectors allow for the selective manipulation of analytes with a finer degree of variation. Embodiments include methods of method of separating particles in a microfluidic channel using a device comprising a microfluidic channel, a source of laser light focused by an optic into the microfluidic channel, and a source of electrical field operationally connected to the microfluidic channel via electrodes so that the laser light and the electrical field to act jointly on the particles in the microfluidic channel. Other devices and methods are disclosed.

This invention relates to compositions of matter, methods, modules and instruments for automated mammalian cell growth and mammalian cell transduction followed by nucleic acid-guided nuclease editing in live mammalian cells.

We describe a method comprising: providing a droplet comprising a plurality of constituents, splitting said droplet into a first droplet and a second droplet, wherein said first droplet comprises a first fraction of said plurality of constituents and said second droplet comprises a second fraction of said plurality of constituents, analysing said constituents of said first fraction of said plurality of constituents in said first droplet, and sorting said second droplet dependent on an outcome of said analysis.

The present disclosure provides methods of preparing tumor infiltrating cells engineered to express a pro-inflammatory polypeptide. The pro-inflammatory polypeptide is expressed from the tumor infiltrating cell to counter a generally immunosuppressive state in and around tumors resulting from an imbalance between the number and activation state of immune effector cells versus those of suppressor cells. Delivering the proinflammatory polypeptide via expression from the TICs, as distinct from systemic administration, reduces side effects from increased inflammation at sides remote from a tumor to be treated.

An integrated package comprising a lab-on-chip (LOC) is disclosed. The LOC includes at least one integrated device having a membrane portion having a membrane opening; the membrane portion having a first side and a second side, the first side opposite the second side, a MEMS portion disposed on the first side of the membrane portion, the MEMS portion having a sharp member disposed on an actuator stage within a MEMS cavity, and a fluidic portion disposed on the second side of the membrane portion, the fluidic portion having a fluidic cavity for flowing a fluid medium within the fluidic portion; and a fluidic cap forming a surface of the fluidic portion of the LOC, the fluidic cap having a fluidic inlet and a fluidic outlet. The method of operating the LOC includes power to the at least one integrated device to capture one or more particles for interrogation.

In situ-generated microfluidic capture structures incorporating a solidified polymer network, methods of preparation and use, compositions and kits therefor are described. Microfluidic capture structures may be advantageously used for assays performed within the microfluidic environment, providing flexibility in assaying micro-objects such as biological cells. Assay reagents and analytes may be incorporated within the microfluidic capture structures.

A system for manipulating electric fields within a microscopic fluid channel includes a fluid channel with an inlet and an outlet to support fluid flow, at least one controllable electric field producer that applies a non-uniform and adjustable electric field to one or more regions of the fluid channel, one or more sensors that measure one or more parameters of a fluid flowing through the fluid channel, and a controller with hardware and software components that receives signals from the one or more sensors representative of values of the one or more parameters and, based on the parameter values, drives one or more actuators to adjust the electric field produced by the plurality of electric field producers. A complex fluid including at least two components flows through the fluid channel, where at least one of the at least two components comprises particles controllable by the non-uniform and adjustable electric field.

A device for sorting bio-particles by image-manipulated electric force includes a first substrate, a second substrate, a fluidic channel, one or more photosensitive layers and an inlet hole. The first substrate has a first conductive electrode, and the second substrate has a second conductive electrode. The second conductive electrode is disposed opposite the first conductive electrode. The fluidic channel is disposed between the first conductive electrode and the second conductive electrode. The photosensitive layer is conformally disposed on at least one of the surfaces of the first conductive electrode and the second conductive electrode. The inlet hole is disposed in the first conductive electrode and the first substrate, where the inlet hole includes a first opening close to the fluidic channel and a second opening away from the fluidic channel, and the surface area of the first opening is greater than the surface area of the second opening.