Georgia Tech Research Corporation

University of Nevada

Cellfe, Inc.

Other

Board of Regents of the Nevada System of Higher Education

Todd A Sulchek

Jesse D Adams

Alexander Alexeev

Stuart C Feigin

Benjamin S Rogers

Gonghao Wang

Sewoon Han

Bushra Tasadduq

Ian Sicher

Peng Qiu

David K Schoenwald

Alla Zamarayeva

Siping Roger Qiu

Damien J Noga

Miguel Calero-garcia

Anna Liu

Aaron C Enten

The present disclosure provides methods and systems for cell processing, including delivery of imaging agents into cells. The methods and systems may comprise the use of a microfluidic device. The microfluidic device may comprise a channel comprising a compressive element. The compressive element may be configured to reduce a volume of the cell and facilitate the formation of one or more transient pores in a cell membrane of the cell. The one or more pores may permit one or more imaging agents to enter the cell. Also provided are modified cells produced using the disclosed methods and systems and methods of imaging the modified cells in a subject.

Methods and systems for cell labeling and imaging

Described herein are methods and systems for cell processing or, more specifically, for introducing various payloads into cells. These methods and systems use a mechanoporation approach in which cells are rapidly compressed and then released to relax while absorbing the payload. More specifically, these methods and systems enable high-throughput mechanoporation with various clogging mitigation features. A cell processing apparatus comprises a shell with an inner shell cylindrical surface, a core with an outer core cylindrical surface, and ridges, supported on and protruding away from one of the inner shell cylindrical surface and the outer core cylindrical surface. The core is disposed inside the shell. The outer core cylindrical surface is concentric with the inner shell cylindrical surface. Each of the ridges forms a ridge gap with the other one of the inner shell cylindrical surface and the outer core cylindrical surface.

Methods and systems for high-throughput cell processing

Embodiments of the present disclosure relate generally to dead-end filtration systems and, more particularly, to pulse-modulated periodic backflush systems and methods for clearing fouling layers in dead-end filtration systems. In some embodiments, a controller may control the flow of fluid in the system from cycling from a forward flow to a reverse flow. In some embodiments, the controller may cycle from forward to reverse flow based on a volumetric flow ratio. Embodiments of the present disclosure describe optimal volumetric flow ratios for optimizing the break of cake in a dead-end filtration system. Embodiments of the present disclosure describe optimal volumetric flow ratios for optimizing recovery percentages of targeted particles.

Pulse-modulated periodic backflush for clearance of fouling layers in dead-end filtration systems

Microfluidic devices for cell sorting or cell fractionation are disclosed. A microfluidic device can comprise one or more inlets, a first wall and a second wall, and two or more outlets. The first and second walls can be substantially planar to each other and the first wall having can have a plurality of ridges protruding from the first wall and defining a compression gap between the ridge and a surface of the second wall. The microfluidic device can also be a cell sorting device for sorting a plurality of cells based on one or more biophysical cellular properties including size, elasticity, viscosity, and/or viscoelasticity wherein the cells are subjected to one or more compressions due to the compression gap. Also disclosed are methods for cell sorting based on a variety of biophysical cellular properties.

Microfluidic devices for cellular sorting

A microchannel for processing cells by compression of the cells including an inlet, ridges and an outlet. Each ridge including a compressive surface and a cell adhesion entity. The outlet configured to remove at least one of a first portion of the cells and a second portion of the cells from the microchannel. Each ridge oriented at an angle of from 25 degrees to 70 degrees relative to a center axis of the microchannel. The cell adhesion entity configured such that the first portion of the cells has a first adhesion property relative to the cell adhesion entity to follow a first trajectory through the microchannel. The cell adhesion entity further configured such that the second portion of the cells has a second adhesion property relative to the cell adhesion entity to follow a second trajectory through the microchannel. The first trajectory is different from the second trajectory.

Systems and methods for continuous sorting of cells based on molecular adhesion

A system for tracking single-cell movement trajectories is disclosed. The system can record, to a plurality of frames, cells (events) within a microfluidic device. Also, the system can identify an event within each frame including whether the event is a single cell or multiple cells. When the event appears differently between frames (e.g., single cell in one frame and multiple cells in another frame), the system can either segment or merge the cell(s). Then, the system can determine a trajectory for the events based on a position of the event in the frames. Further, the system can determine cell properties based on the trajectory of the events.

Systems and methods for tracking single-cell movement trajectories

Embodiments of the present disclosure can include a method comprising: providing a plurality of cells to a microchannel, the microchannel coated in at least one cell adhesion entity and comprising a compressive surface and a first outlet, the compressive surface defining a compression gap, flowing the plurality of cells through the microchannel, wherein the flowing comprises: compressing the plurality of cells underneath the compressive surface; and exposing the plurality of cells to the at least one cell adhesion entity, wherein the exposing causes a first portion of the cells having a first adhesion property to temporarily bind to the cell adhesion entity; and collecting the first portion of cells at the first outlet; wherein the compression gap has a height of from 75% to 95% an average diameter of the plurality of cells.

Methods for continuous sorting of cells based on molecular adhesion

Embodiments of the present disclosure can include a method for convective intracellular delivery including providing cells and molecules to a microchannel having compressive surfaces, wherein the compressive surfaces define compression gaps having a height of from 20 and 80% of the average cell diameter; and a plurality of relaxation spaces disposed between the compressive surfaces; flowing the cell medium through the microchannel, wherein as the cell medium flows through the microchannel, the plurality of cells undergo a convective intracellular delivery process comprising: compressing the plurality of cells, wherein the compressing causes the plurality of cells to undergo a loss in intracellular volume (V); and passing the plurality of cells to a first relaxation space, wherein the plurality of cells undergo a gain in volume (V) and absorb a portion of the plurality of molecules.

Methods for convectively-driven intracellular delivery

A disclosed chemical detection system for detecting a target material, such as an explosive material, can include a cantilevered probe, a probe heater coupled to the cantilevered probe, and a piezoelectric element disposed on the cantilevered probe. The piezoelectric element can be configured as a detector and/or an actuator. Detection can include, for example, detecting a movement of the cantilevered probe or a property of the cantilevered probe. The movement or a change in the property of the cantilevered probe can occur, for example, by adsorption of the target material, desorption of the target material, reaction of the target material and/or phase change of the target material. Examples of detectable movements and properties include temperature shifts, impedance shifts, and resonant frequency shifts of the cantilevered probe. The overall chemical detection system can be incorporated, for example, into a handheld explosive material detection system.

Cantilevered probe detector with piezoelectric element

The invention provides a liquid cell for an atomic force microscope. The liquid cell includes a liquid cell housing with an internal cavity to contain a fluid, a plurality of conductive feedthroughs traversing the liquid cell housing between the internal cavity and a dry side of the liquid cell, a cantilevered probe coupled to the liquid cell housing, and a piezoelectric drive element disposed on the cantilevered probe. The cantilevered probe is actuated when a drive voltage is applied to the piezoelectric drive element through at least one of the conductive feedthroughs. A method of imaging an object in a liquid medium and a method of sensing a target species with the liquid cell are also disclosed.

Growing community of inventors

Oakland, CA, United States of America

Todd A Sulchek