University of California

Michael A Teitell

Pei-Yu E Chiou

Ting-Hsiang Sherry Wu

Jason C Reed

James K Gimzewski

Yi-Chien Wu

Yu-Chun Kung

Sung-Yong Park

Thomas A Zangle

Yue Chen

Carla M Koehler

Daina Burnes Linton

Ting-Hsiang S Wu

Owen N Witte

Sheraz Kalim Butt

Ming-Yu Lin

Geng Wang

Jessica Zhou

Xiongfeng Zhu

Xing Haw Marvin Tan

Thang Nguyen

Owen M Witte

Samuel A Hasson

Kiyoko Miyata

Deepa Dabir

Ting-Hsiang Wu

Pei-Yu Chiou

Methods, devices, and systems are provided for the delivery of agents (e.g., nucleic acids, proteins, organic molecules, organelles, antibodies or other ligands, etc.) into live cells and/or the extraction of the same from said cells. In various embodiments the photothermal platforms and systems incorporating such photothermal platforms are provided that permit efficient, high-throughput cargo delivery into live cells.

High-throughput cargo delivery into live cells using photothermal platforms

In certain embodiments methods of identifying T cell receptors that respond to specific target cell antigens are provided, where the methods comprise providing a substrate bearing a plurality of target cells (e.g., mammalian cells); contacting the target cells on the substrate with CD8+ T cells; and using label-free optical imaging to identify an increase in mass of a T-cell and/or a decrease in mass of a target cell, where an increase in mass of a T cell and/or a decrease in mass of a target cell is an indicator that said T cell bears a T cell receptor activated by antigens presented on said target cell.

Identifying desirable T lymphocytes by change in mass responses

In various embodiments, method and devices for delivering large cargos (e.g., organelles, chromosomes, bacteria, and the like) into cells are provided. In certain embodiments method of delivering a large cargo into eukaryotic cells, are provided that involve providing eukaryotic cells disposed on one side of a porous membrane; providing the cargo to be delivered in a solution disposed in a reservoir chamber on the opposite side of the porous membrane; and applying pressure to the reservoir chamber sufficient to pass the cargo through pores comprising said porous membrane wherein said cargo passes through cell membranes and into the cells.

Efficient delivery of large cargos into cells on a porous substrate

New platform technologies to actuate and sense force propagation in real-time for large sheets of cells are provided. In certain embodiments the platform comprises a device for the measurement of mechanical properties of cells or other moieties, where device comprises a transparent elastic or viscoelastic polymer substrate disposed on a rigid transparent surface; and a plurality of micromirrors disposed on or in said polymer substrate, wherein the reflective surfaces of the micromirrors are oriented substantially parallel to the surface of said polymer substrate. In certain embodiments the device comprises more than about 1,000,000, or more than about 10,000,000 micromirrors. In certain embodiments the micromirrors comprise a magnetic layer and/or a diffraction grating.

Single-pixel optical technologies for instantly quantifying multicellular response profiles

Methods, devices, and systems are provided for the delivery of agents (e.g., nucleic acids, proteins, organic molecules, organelles, antibodies or other ligands, 5 etc.) into live cells and/or the extraction of the same from said cells. In various embodiments the photothermal platforms and systems incorporating such photothermal platforms are provided that permit efficient, high-throughput cargo delivery into live cells.

Selecting and isolating desirable t lymphocytes by change in mass responses

The present invention provides optical systems and methods for determining a characteristic of a cell, such as cell type, cellular response to a biochemical event, biological state and the like. The methods typically involve using interferometry to observe membrane properties in a cell and then use this information to determine one or more characteristics of a cell. The methods of the invention are useful for applications such as drug screening as well as diagnostic techniques.

Optical cytometry to determine cell mass changes in response to a biologically active agent

In various embodiments methods are provided for delivering an agent of interest (e.g., protein, antibody, nucleic acid) into cells. In certain embodiments the method comprises contacting the cells with anisotropic magnetic particles in the presence of the agent; and applying a substantially uniform magnetic field to said magnetic particles where movement of said particles induced by said magnetic field introduces transient openings into said cell facilitating entry of said agent of interest into said cells.

Methods for efficient intracellular delivery using anisotropic magnetic particles

Methods and devices for the formation and/or merging of droplets in microfluidic systems are provided. In certain embodiments a microfluidic droplet merger component is provided that comprises a central channel comprising a plurality of elements disposed and spaced to create a plurality of lateral passages that drain a carrier fluid out of a fluid stream comprising droplets of a first fluid contained in the carrier fluid; and a deformable lateral membrane valve disposed to control the width of said center channel.

High-speed on demand microfluidic droplet generation and manipulation

The present invention provides compounds that modulate protein translocation in mitochondria, compositions thereof, and methods of identifying, making and using these.

Modulators of mitochondrial protein import

This invention provides novel tools for surgery on single cells and substrates/devices for delivery of reagents to selected cells. In certain embodiments the substrates comprise a surface comprising one or more orifices, where nanoparticles and/or a thin film is deposited on a surface of said orifice or near said orifice, where the nanoparticles and/or a thin film are formed of materials that heat up when contacted with electromagnetic radiation. In certain embodiments the pores are in fluid communication with microchannels containing one or more reagents to be delivered into the cells.

Photothermal substrates for selective transfection of cells

Methods and devices for the formation of droplets of a first fluid in a second fluid and the encapsulation of particles or cells within such droplets are disclosed. Impetus for droplet formation is provided by the creation of a transient bubble, which may be induced using a pulsed laser. Droplet volume and the frequency at which droplets are formed can be controlled by modulation of the pulsed laser. The disclosed methods and devices are particularly suitable for use in microfluidic devices.

High-speed on demand droplet generation and single cell encapsulation driven by induced cavitation

In certain embodiments this invention provides a pulsed-laser triggered microfluidic switching mechanism that can achieve a switching time of 70 &#x3bc;s. This switching speed is two orders of magnitude shorter than that of the fastest switching mechanism utilized in previous &#x3bc;FACS.

Pulsed laser triggered high speed microfluidic switch and applications in fluorescent activated cell sorting

A central question in cancer therapy is how individual cells within a population of tumor cells respond to drugs designed to arrest their growth. However, the absolute growth of cells, their change in physical mass, whether cancerous or physiologic, is difficult to measure directly with traditional techniques. Embodiments of the invention provide live cell interferometry (LCI) for rapid, realtime quantification of cell mass in cells exposed to a changing environment. Overall, LCI provides a conceptual advance for assessing cell populations to identify, monitor, and measure single cell responses, such as to therapeutic drugs.

Growing community of inventors

Tarzana, CA, United States of America

Michael A Teitell