Innovative Micro Technology

Owl Biomedical, Inc.

Optical Coating Laboratory, Inc.

Miltenyi Biotec B.v. Co., Kg

Nguyen, Hung D.

Foster, John S.

Harley, John C.

Rubel, Paul John

Martin, Richard T.

John Stuart Foster

Paul Rubel

Kevin Shields

Daryl Grummitt

Mehran Hoonejani

Jeffery Frank Summers

Richard Thomas Martin

John Harley

Jaquelin K Spong

Nicholas C Martinez

John Wesley Stocker

Patrick Edward Feierabend

Christopher S Gudeman

Kimon Rybnicek

Gregory A Carlson

Steven H Hovey

Kimberly L Turner

Douglas L Thompson

Andrew Dexter Wallis

Stefan Miltenyi

Alok Paranjpye

Hung P Nguyen

Ralf-Peter Peters

Bryant P Hichwa

Eiad Kabaha

Jan Boddenberg

Mark A Naivar

Kamala Qalandar

Michael James Shillinger

Paulo Silveira Da Motta

Jeffrey F Summers

James P Linton

Yareeve Zemel

Markus Nagel

Christian Peth

Ian R Johnston

Robert Pinard

Hansueli Meyer

Lily Li

Tara Jean Rybnicek

Matthias Wahl

Kimberley L Turner

Alok Paranjypye

Donald C Liu

Paul J Rubel

John C Harley

Hung Nguyen

Martin BÜSCHER

Daryl W Grummitt

Richard T Martin

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 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. The target particles may be identified by a marker-free signal such as axial light loss to identify highly pigmented particles.

Particle manipulation system with out-of-plane channel using axial light loss

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 MEMS-based cell sorting system is disclosed, which uses a novel combination of features to accomplish the cell sorting in the microfabricated channels housed in a disposable cartridge. The MEMS-based cell sorting system may include a microfabricated cell sorting valve that is responsive to an applied magnetic field. The MEMS-based cell sorting system may further include an electromagnet that generates a magnetic field to actuate the microfabricated cell sorting valve. The electromagnet may have a design which allows it to create a very localized magnetic field while having adequate thermal properties to operate reliably.

Cell sorting system using electromagnetic solenoid

A MEMS-based cell sorter is disclosed, which uses a novel combination of features to accomplish the cell sorting using a microfabricated cell sorting valve housed in a disposable cartridge. The features include an interposer that provides fluid communication between the microfluidic passages in the silicon substrate and a plurality of fluid reservoirs in the cartridge, including a sample, sort and waste reservoir The disposable cartridge may include other features that assist in the handling of small volumes of fluids, such as a siphon region in the sort reservoir and funnel-shaped regions in the sample and waste reservoirs. A mixing mechanism may be provided for stirring the contents of the sample reservoir.

Cell sorting system using microfabricated components

A particle separation system uses a MEMS-based, microfabricated particle manipulation device which has an inlet channel, output channels, and a movable member formed on a substrate to sort one or more target particle from a sample stream. The system may include an interposer that receives the sorted particle and dispenses a carrier fluid with it to form a liquid droplet containing the particle. The droplet may then be dispensed to a microtiter plate, such that each well in the titer plate may contain a single target particle. The system may be used to separate individual biological cells, such as T cells, B cells, stem cells, cancer cells and sperm cells for further manipulation.

MEMS-based single particle separation system

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.

Particle manipulation system with cytometric capability

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

Growing community of inventors

Santa Barbara, CA, United States of America

John Stuart Foster