University of California

Other

California Institute of Technology

Chih-Ming Ho

Ren Sun

Pak Kin Wong

Fuqu Yu

Yu-Chong Tai

Marcus Aaron Horwitz

Bai-Yu Lee Clemens

Chang Liu

Daniel L Clemens

Xianting Ding

Theodore Kee

Aleidy Marlene Silva Vite

Chang-Jin Kim

Fan-Gang Tseng

Yong Qin Chen

Fukang Jiang

James Liao

Amish Desai

Denny K Miu

Po-Hao Adam Huang

Tom Tsao

Wen J Li

Jeremy Tzong-Shyng Leu

Raanan Miller

Jin-Biao Huang

Joanne Helene Deval

Yi-Kuen Lee

Patrick Tabeling

Minghsun Liu

Tza-Huei Wang

Jun Huang

Jeffrey F Miller

Yitong Zhao

A method includes: (1) applying stimulations to a system, wherein applying the stimulations includes modulating, over time, characteristics of the stimulations; (2) measuring a time-varying response of the system to the stimulations; (3) fitting the time-varying response of the system into a model of the system; and (4) using the model of the system, identifying an optimized combination of characteristics of the stimulations to yield a desired response of the system.

Real-time feedback system control technology platform with dynamically changing stimulations

The present invention is directed to methods of treating tuberculosis by providing a pharmaceutically effective amount of a combination of drug compounds.

Multi-drug therapies for tuberculosis treatment

The present invention is directed to methods, compositions, and systems for the production of fatty acids (FAs). Specifically, the disclosed methods, compositions, and systems incorporate algal cell lysates, providing a cell-free environment that generates high levels of FAs for extended periods of time with the addition of liquid media and a carbon source.

Fatty acid production in cell-free systems

A method for optimization of a response of a biological system includes: (1) obtaining measurements of a biological system in response to varying concentrations of drugs in a drug combination; (2) fitting the measurements into a model of the biological system; and (3) using the model of the biological system, predicting concentrations of the drugs in the drug combination to yield an optimized response of the biological system.

Apparatus and methods for manipulation and optimization of biological systems

The invention provides systems and methods for manipulating biological systems, for example to elicit a more desired biological response from a biological sample, such as a tissue, organ, and/or a cell. In one aspect, the invention operates by efficiently searching through a large parametric space of stimuli and system parameters to manipulate, control, and optimize the response of biological samples sustained in the system. In one aspect, the systems and methods of the invention use at least one optimization algorithm to modify the actuator's control inputs for stimulation, responsive to the sensor's output of response signals. The invention can be used, e.g., to optimize any biological system, e.g., bioreactors for proteins, and the like, small molecules, polysaccharides, lipids, and the like. Another use of the apparatus and methods includes is for the discovery of key parameters in complex biological systems.

The invention provides systems and methods for manipulating, e.g., optimizing and controlling, biological systems, e.g., for eliciting a more desired biological response of biological sample, such as a tissue, organ, and/or a cell. In one aspect, systems and methods of the invention operate by efficiently searching through a large parametric space of stimuli and system parameters to manipulate, control, and optimize the response of biological samples sustained in the system, e.g., a bioreactor. In alternative aspects, systems include a device for sustaining cells or tissue samples, one or more actuators for stimulating the samples via biochemical, electromagnetic, thermal, mechanical, and/or optical stimulation, one or more sensors for measuring a biological response signal of the samples resulting from the stimulation of the sample. In one aspect, the systems and methods of the invention use at least one optimization algorithm to modify the actuator's control inputs for stimulation, responsive to the sensor's output of response signals. The compositions and methods of the invention can be used, e.g., to for systems optimization of any biological manufacturing or experimental system, e.g., bioreactors for proteins, e.g., therapeutic proteins, polypeptides or peptides for vaccines, and the like, small molecules (e.g., antibiotics), polysaccharides, lipids, and the like. Another use of the apparatus and methods includes combination drug therapy, e.g. optimal drug cocktail, directed cell proliferations and differentiations, e.g. in tissue engineering, e.g. neural progenitor cells differentiation, and discovery of key parameters in complex biological systems.

A method and system for specifically detecting perfectly matched probe-target hybrids by annealing a hairpin-based probe to a nucleic acid target under conditions favoring the formation of perfectly matched targets over mismatched targets, and electrochemically detecting the annealed probe. Sensitivity of detection can be enhanced by catalyzed reporter deposition of probe signal prior to electrochemical detection. Specificity can be enhanced by including hairpin-based competitor probes in the annealing step. The detection assay is particularly applicable to typing single nucleotide polymorphisms by DNA sandwich hybridization.

Electrochemical detection of mismatch nucleic acids

An improved chemical mixing micro-device with features on the micro- and nano-scale. The micro-device is comprised of at least one chemical inlet port and one chemical outlet port, a micro-evaporator, a micro-chamber and a micro-initiator. Also, a method of mixing at least one chemical in an evaporative mixing and/or reacting chamber is disclosed.

Control devices for evaporative chemical mixing/reaction

A micro mixer for use in a microdevice which utilizes time-varying force fields to induce bulk fluid and/or sample component motion leading to homogenization of sample components. Time-varying force fields employed includes at least one of a physical displacement field, electrical field, pressure field or magnetic field to generate transverse forces which induce the mixing of samples within the micro mixer.

Micro chaotic mixer

An apparatus and method for forming a bubble within a microchannel of a microinjector to function as a valve mechanism between the chamber and manifold, that provides for a high resistance to liquid exiting the chamber through the manifold during fluid ejection through an orifice and that also provides a low resistance to refilling of liquid into the chamber after ejection of fluid and collapse of the bubble. This effectively minimizes cross talk between adjacent chambers and increases injection frequency of the microinjector. The formation of a second bubble within the chamber coalesces with a first formed bubble between the chamber and manifold to abruptly terminate the ejection of fluid, thereby eliminating satellite droplets.

Apparatus for using bubbles as virtual valve in microinjector to eject fluid

Apparatus and method for using bubble as virtual valve in microinjector

An integrated circuit, or microelectromechanical structure is defined onto a contour surface by utilizing a flexible mask upon which photolithographic patterns are first defined using conventional planar photolithographic techniques. The contour surface is provided with a thin film uniformly distributed on the surface and then the flexible mask is aligned with the contour substrate. Alignments are made through multiple stages of yaw alignment, translation alignment and rotational alignment. Once the mask is aligned with contour substrate it is then subjected while rotating to developing field, such as uniform illumination of ultraviolet light shining on the side of the contour substrate as it is rotated in the illumination field. The developed photoresist layer disposed on the surface of the contour substrate is thus developed and the underlying film etched according to the patterned mask in a manner similar to a conventional planar photolithography. Multiple layers are thus disposed masked and etched to result in complex multilayered integrated circuit and/or microelectromechanical devices disposed on the contour surface of a macromechanical component or structure.

Method for aligning and forming microelectromechanical systems (MEMS)

A micromachined hot-wire anemometer having fast response times and higher sensitivities than conventional hot-wire anemometers is provided by micromachining doped polysilicon wires carried on silicon supports cantilevered from a substrate including one or more insulating layers disposed between said substrate and supports. The micromachined polysilicon hot-wire anemometer is fabricated using surface micromachining techniques. A shear stress sensor is micromachined to define a thin diaphragm over a cavity defined in a substrate underlying the diaphragm. The cavity is evacuated, sealed, and a thermistor disposed over the diaphragm. The thermistor is thus thermally insulated from the substrate and provides a low profile shear stress sensor for measuring flow rates in boundary layers above a flow surface.

Micromachined hot-wire shear stress sensor

A surface micromachined micromagnetic actuator is provided with a flap capable of achieving large deflections above 100 microns using magnetic force as the actuating force. The flap is coupled by one or more beams to a substrate and is cantilevered over the substrate. A Permalloy layer or a magnetic coil is disposed on the flap such that when the flap is placed in a magnetic field, it can be caused to selectively interact and rotate out of the plane of the magnetic actuator. The cantilevered flap is released from the underlying substrate by etching out an underlying sacrificial layer disposed between the flap and the substrate. The etched out and now cantilevered flap is magnetically actuated to maintain it out of contact with the substrate while the just etched device is dried in order to obtain high release yields.

Growing community of inventors

Brentwood, CA, United States of America

Chih-Ming Ho