Abstract: 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.

Abstract: A MEMS-based particle manipulation system which uses a particle manipulation stage and optical confirmation of the manipulation. The optical confirmation may be camera-based, and 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, fluid valve, which sorts a target particle from non-target particles in a fluid stream. The optical confirmation stage is disposed in the microfabricated fluid channels at the input and output of the microfabricated sorting valve. Deep learning techniques are brought to bear on the camera output to increase speed, accuracy and reliability.

Abstract: A cell sorting device is disclosed, wherein the device includes a sorting magnet and at least one particle manipulation device, wherein the particle manipulation device is formed on a surface of a fabrication substrate. The device may include at least one fluid channel, wherein the sorting magnet and the particle manipulation device are in fluid communication with one another through at least one fluid channel. A method of sorting cells from a first cell suspension is also disclosed, The method may include a) magnetic labeling of first target cells and removal of the non-target cells by applying magnetic fields to obtain a second cell suspension; b) fluorescence-activated labeling of second target cells present in the second cell suspension and separating the fluorescence-activated second target cells from the not labeled cells to obtain a third cell suspension.

Abstract: A microfabricated droplet dispensing structure is described, which may include a MEMS microfluidic fluidic valve, configured to open and close a microfluidic channel. The opening and closing of the valve may separate a target biological particle containing genomic material, and a bead from a sample stream, and direct these two particle into a single droplet formed at the edge of the substrate. The droplet may then be encased in a sheath flow of an immiscible fluid, and provided to a downstream workflow.

Abstract: A microfabricated particle manipulation system, wherein a target particle is pierced by a microfabricated actuator or by a microfabricated knife edge. In either case, the particle membrane is altered, so as to allow material to traverse the membrane. The device may be used to extract cellular material from inside a cell, or to transfect a cell with foreign material.

Abstract: A microfabricated droplet dispensing structure is described, which may include a MEMS microfluidic fluidic valve, configured to open and close a microfluidic channel. The opening and closing of the valve may separate a target biological particle containing genomic material, and a bead from a sample stream, and direct these two particle into a single droplet formed at the edge of the substrate. The droplet may then be encased in a sheath flow of an immiscible fluid, and provided to a sequencing module. The sequencing module may sequence the genomic material and/or an identifying barcode attached to the bead.

Abstract: A microfabricated droplet dispensing structure is described, which may include a MEMS microfluidic fluidic valve, configured to open and close a microfluidic channel. The opening and closing of the valve may separate a target particle and a bead from a sample stream, and direct these two particle into a single droplet formed at the edge of the substrate. The droplet may then be encased in a sheath flow of an immiscible fluid.

Abstract: A cell sorting device is disclosed, wherein the device includes a magnetic separation “debulking” stage followed a microfabricated fluid valve. The magnetic separation stage may use a sorting magnet and sort particle using magnetic beads attached to the particles. The device may include at least one fluid channel, wherein the sorting magnet and the particle manipulation device are in fluid communication with one another through at least one fluid channel. A method of sorting cells from a first cell suspension is also disclosed, The method may include a) magnetic labeling of first target cells and removal of the non-target cells by applying magnetic fields to obtain a second cell suspension; b) fluorescence-activated labeling of second target cells present in the second cell suspension and separating the fluorescence-activated second target cells from the not labeled cells to obtain a third cell suspension.

Abstract: A particle manipulation system uses a MEMS-based, microfabricated particle manipulation device which has a sample inlet channel, output channels, and a movable member formed on a substrate. The device may be used to separate a target particle from non-target material in a sample stream. In order to improve the sorter speed, accuracy or yield, the particle manipulation system may also include a microfluidic structure which focuses the target particles in a particular portion of the sample inlet channel. The particle manipulation device may have two separate sort output channels, wherein the sort channel used depends on the characteristics of the sort pulse delivered to the micromechanical particle manipulation device.

Abstract: A particle manipulation system uses a MEMS-based, microfabricated particle manipulation device which has a sample inlet channel, output channels, and a movable member formed on a substrate. The device may be used to separate a target particle from non-target material in a sample stream. In order to improve the sorter speed, accuracy or yield, the particle manipulation system may also include a microfluidic structure which focuses the target particles in a particular portion of the sample inlet channel. The particle manipulation device may have two separate sort output channels, wherein the sort channel used depends on the characteristics of the sort pulse delivered to the micromechanical particle manipulation device.

Abstract: A cell sorting device is disclosed, wherein the device includes a sorting magnet and at least one particle manipulation device, wherein the particle manipulation device is formed on a surface of a fabrication substrate. The device may include at least one fluid channel, wherein the sorting magnet and the particle manipulation device are in fluid communication with one another through at least one fluid channel. A method of sorting cells from a first cell suspension is also disclosed, The method may include a) magnetic labeling of first target cells and removal of the non-target cells by applying magnetic fields to obtain a second cell suspension; b) fluorescence-activated labeling of second target cells present in the second cell suspension and separating the fluorescence-activated second target cells from the not labeled cells to obtain a third cell suspension.

Abstract: A microfabricated droplet dispensing structure is described, which may include a MEMS microfluidic fluidic valve, configured to open and close a microfluidic channel. The opening and closing of the valve may separate a target particle and a bead from a sample stream, and direct these two particle into a single droplet formed at the edge of the substrate. The droplet may then be encased in a sheath flow of an immiscible fluid.

Abstract: A MEMS-based particle manipulation system which uses a particle manipulation stage and optical confirmation of the manipulation. The optical confirmation may be camera-based, and 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, fluid valve, which sorts a target particle from non-target particles in a fluid stream. The optical confirmation stage is disposed in the microfabricated fluid channels at the input and output of the microfabricated sorting valve. Deep learning techniques are brought to bear on the camera output to increase speed, accuracy and reliability.

Abstract: A microfabricated particle manipulation system, wherein a target particle is pierced by a microfabricated actuator or by a microfabricated knife edge. In either case, the particle membrane is altered, so as to allow material to traverse the membrane. The device may be used to extract cellular material from inside a cell, or to transfect a cell with foreign material.

Abstract: A MEMS-based particle manipulation system which uses a particle manipulation stage and optical confirmation of the manipulation. The optical confirmation may be camera-based, and 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, fluid valve, which sorts a target particle from non-target particles in a fluid stream. The optical confirmation stage is disposed in the microfabricated fluid channels at the input and output of the microfabricated 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.

Abstract: A particle manipulation system uses a MEMS-based, microfabricated particle manipulation device which may be used to separate a target particle from non-target material in a sample stream. In order to improve the sorter speed, accuracy or yield, the particle manipulation system may also include a microfluidic structure which focuses the target particles in a particular portion of the sample inlet channel. The particle manipulation device may have two separate sort output channels, wherein the sort channel used depends on the characteristics of the sort pulse delivered to the micromechanical particle manipulation device. Because of the improved focusing and pulse details, a droplet may be formed which contains a single particle, which may also be barcoded with an identifiable signature bead.

Abstract: Described here is a microfabricated particle sorting device that uses a transient pulse of fluidic pressure to deflect the target particle. The transient pulse may be generated by a microfabricated (MEMS) actuator, which pushes a volume of fluid into a channel, or sucks a volume of fluid from the channel. The transient pressure pulse may divert a target particle into a sort channel.

Abstract: Described here is a microfabricated particle filtering structure having at least one microchannel formed in a surface of a silicon substrate. The filter structure uses a plurality of barriers formed in at least one microchannel, wherein a distance between the closest barriers is small enough to capture the particulate debris but allow the sample fluid to flow, and a transparent layer that covers the silicon substrate, and the plurality of barriers. The debris captured by the barriers may be analyzable through the transparent layer, helping in determining the source of the debris.

Abstract: A particle manipulation system uses a MEMS-based, microfabricated particle manipulation device which has an inlet channel, output channels, and a movable member formed on a substrate. The movable member moves parallel to the fabrication plane, as does fluid flowing in the inlet channel. The movable member separates a target particle from the rest of the particles, diverting it into an output channel. However, at least one output channel is not parallel to the fabrication plane. The device may be used to separate a target particle from non-target material in a sample stream. In the event that the microfabricated particle manipulation device malfunctions as a result of a particle of debris becoming lodged in the microfabricated particle manipulation device, the system may invoke a recovery algorithm, that includes vibrating the microfabricated particle manipulation device using a pulse train at a frequency near its mechanical resonance.

Abstract: Described here is a microfabricated particle sorting device that uses a transient pulse of fluidic pressure to deflect the target particle. The transient pulse may be generated by a microfabricated (MEMS) actuator, which pushes a volume of fluid into a channel, or sucks a volume of fluid from the channel. The transient pressure pulse may divert a target particle into a sort channel.