Owl Biomedical, Inc.

Kevin Shields

John Stuart Foster

Mehran Hoonejani

Nicholas C Martinez

Stefan Miltenyi

Mark A Naivar

Jaquelin K Spong

Kimberly L Turner

Kamala Qalandar

Yareeve Zemel

Daryl Grummitt

Robert Pinard

Hansueli Meyer

Matthias Wahl

Lily Li

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.

Microfabricated droplet dispensor with immiscible fluid and genetic sequencer

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.

Particle manipulation system with camera/classifier confirmation and deep learning algorithm

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.

Particle manipulation system with multisort valve

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.

Microfabricated droplet dispensor with immiscible fluid

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.

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.

Particle manipulation system with camera confirmation

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.

Microfabricated cell sorter using pressure pulse

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.

Particle manipulation system with out-of-plane channel and recovery algorithm

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. This focusing element may include cavities of variable cross section along the channel length. In addition, a filtering element may also be included upstream of the focusing element.

Particle manipulation system with out-of-plane channel and variable cross section focusing element

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. The target particle may be, for example, a stem cell, zygote, a cancer cell, a T-cell, a component of blood, bacteria or DNA sample, for example. The particle manipulation system may also include a microfluidic structure which focuses the target particles in a particular portion of the inlet channel.

Particle manipulation system with out-of-plane channel and focusing element

Particle manipulation system with out-of-plane channel

A MEMS-based particle manipulation system which uses a particle manipulation stage and a sensor to detect when the sample volume is exhausted or nearly exhausted. The sensor sends a signal to a fluid control means that reverses the pressure between one of the output channels and the input channels, to keep the surfaces wet with a volume of the sample fluid. This volume can be maintained in the channel until an operator intervenes, or it can be repeatedly shuttled back and forth between the input channel and an output channel. By keeping the channels wet, material from the sample stream does not become adhered to the channel walls, which might otherwise irreversibly change or damage the device.

Particle manipulation system with stay-wet algorithm

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 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 valve. By reversing the flow from output to input, the same laser interrogation region may be used to perform the cytometry. The cytometry may be performed throughout the sorting process to optimize or control the sorting, or may be performed afterward to allow a multi-pass, sequential sort to be performed on the same sample.

Growing community of inventors

Santa Barbara, CA, United States of America

Kevin Shields