Showing papers by "Stephen R. Quake published in 2001"

Dynamic pattern formation in a vesicle-generating microfluidic device.

Abstract: Spatiotemporal pattern formation occurs in a variety of nonequilibrium physical and chemical systems. Here we show that a microfluidic device designed to produce reverse micelles can generate complex, ordered patterns as it is continuously operated far from thermodynamic equilibrium. Flow in a microfluidic system is usually simple—viscous effects dominate and the low Reynolds number leads to laminar flow. Self-assembly of the vesicles into patterns depends on channel geometry and relative fluid pressures, enabling the production of motifs ranging from monodisperse droplets to helices and ribbons.

Microfabricated Crossflow Devices and Methods

Abstract: A microfluidic device for analyzing and/or sorting biological materials (e.g., molecules such as polynucleotides and polypeptides, including proteins and enzymes; viruses and cells) and methods for its use are provided. The device and methods of the invention are useful for sorting particles, e.g. virions. The invention is also useful for high throughput screening, e.g. combinatorial screening. The microfluidic device comprises a main channel and an inlet region in communication with the main channel at a droplet extrusion region. Droplets of solution containing the biological material are deposited into the main channel through the droplet extrusion region. A fluid different from and incompatible with the solution containing the biological material flows through the main channel so that the droplets containing the biological material do not diffuse or mix. Biological material within the droplets can be analyzed and/or sorted by detecting a predetermined characteristic of the biological sample in each droplet and sorting the droplet accordingly.

Integrated active flux microfluidic devices and methods

Abstract: The invention relates to a microfabricated device for the rapid detection of DNA, proteins or other molecules associated with a particular disease. The devices and methods of the invention can be used for the simultaneous diagnosis of multiple diseases by detecting molecules (e.g. amounts of molecules), such as polynucleotides (e.g., DNA) or proteins (e.g., antibodies), by measuring the signal of a detectable reporter associated with hybridized polynucleotides or antigen/antibody complex. In the microfabricated device according to the invention, detection of the presence of molecules (i.e., polynucleotides, proteins, or antigen/antibody complexes) are correlated to a hybridization signal from an optically-detectable (e.g. fluorescent) reporter associated with the bound molecules. These hybridization signals can be detected by any suitable means, for example optical, and can be stored for example in a computer as a representation of the presence of a particular gene. Hybridization probes can be immobilized on a substrate that forms part of or is exposed to a channel or channels of the device that form a closed loop, for circulation of sample to actively contact complementary probes. Universal chips according to the invention can be fabricated not only with DNA but also with other molecules such as RNA, proteins, peptide nucleic acid (PNA) and polyamide molecules.

A Microfabricated Rotary Pump

Abstract: Because microfluidic devices operate at low Reynolds number, many fluidic operations are limited by diffusion. We have developed a microfabricated rotary pump and demonstrated that active mixing can be used to overcome the slow diffusion process in two applications. First, we showed that mixing of reagents could be efficiently accomplished for objects of a wide range of diffusion constants. Second, we showed how reaction kinetics of a surface-binding assay can be enhanced by nearly two orders of magnitude.

Method and apparatus for analysis and sorting of polynucleotides based on size

Abstract: The invention relates to a microfabricated device and methods of using the device for analyzing and sorting polynucleotide molecules by size.

Apparatus and methods for conducting assays and high throughput screening

Abstract: The present invention provides microfluidic devices and methods for using the same. In particular, microfluidic devices of the present invention are useful in conducting a variety of assays and high throughput screening. Microfluidic devices of the present invention include elastomeric components and comprise a main flow channel; a plurality of branch flow channels; a plurality of control channels; and a plurality of valves. Preferably, each of the valves comprises one of the control channels and an elastomeric segment that is deflectable into or retractable from the main or branch flow channel upon which the valve operates in response to an actuation force applied to the control channel.

Microfluidic devices and methods of use

Abstract: A microfluidic device comprises pumps, valves, and fluid oscillation dampers. In a device employed for sorting, an entity is flowed by the pump along a flow channel through a detection region to a junction. Based upon an identity of the entity determined in the detection region, a waste or collection valve located on opposite branches of the flow channel at the junction are actuated, thereby routing the entity to either a waste pool or a collection pool. A damper structure may be located between the pump and the junction. The damper reduces the amplitude of oscillation pressure in the flow channel due to operation of the pump, thereby lessening oscillation in velocity of the entity during sorting process. The microfluidic device may be formed in a block of elastomer material, with thin membranes of the elastomer material deflectable into the flow channel to provide pump or valve functionality.

Method of making a microfabricated elastomeric valve

Abstract: A method of fabricating an elastomeric structure, comprising: forming a first elastomeric layer on top of a first micromachined mold, the first micromachined mold having a first raised protrusion which forms a first recess extending along a bottom surface of the first elastomeric layer; forming a second elastomeric layer on top of a second micromachined mold, the second micromachined mold having a second raised protrusion which forms a second recess extending along a bottom surface of the second elastomeric layer; bonding the bottom surface of the second elastomeric layer onto a top surface of the first elastomeric layer such that a control channel forms in the second recess between the first and second elastomeric layers; and positioning the first elastomeric layer on top of a planar substrate such that a flow channel forms in the first recess between the first elastomeric layer and the planar substrate.

Solid immersion lens structures and methods for producing solid immersion lens structures

Abstract: A microlens structure such as a solid immersion lens structure is a radiation transmissive pliant elastomer cast to a desired shape and smoothness. A method for construction of a solid immersion lens structure includes providing a mold defining a lens shaped cavity in which a solid immersion lens is cast, casting a translucent liquid elastomeric material into the lens cavity, permitting the elastomeric material to set to form the solid immersion lens portion and removing the solid immersion lens portion from the mold. A specific material for use as the solid immersion lens is a translucent silicone elastomer of a refractive index greater than n=1.4, such as General Electric RTV 615.

Combinatorial array for nucleic acid analysis

Abstract: This invention relates to an array, including a universal micro-array, for the analysis of nucleic acids, such as DNA. The devices and methods of the invention can be used for identifying gene expression patterns in any organism. More specifically, all possible oligonucleotides (n-mers) necessary for the identification of gene expression patterns are synthesized. According to the invention, n is large enough to give the specificity to uniquely identify the expression pattern of each gene in an organism of interest, and is small enough that the method and device can be easily and efficiently practised and made. The invention provides a method of analyzing molecules, such as polynucleotides (e.g., DNA), by measuring the signal of an optically-detectable (e.g., fluorescent, ultraviolet, radioactive or color change) reporter associated with the molecules. In a polynucleotide analysis device according to the invention, levels of gene expression are correlated to a signal from an optically-detectable (e.g. fluorescent) reporter associated with a hybridized polynucleotide. The invention includes an algorithm and method to interpret data derived from a micro-array or other device, including techniques to decode or deconvolve potentially ambiguous signals into unambiguous or reliable gene expression data.

Electrostatic valves for microfluidic devices

Abstract: Valve structures formed in elastomer material are electrostatically actuated by applying voltage to a flexible, electrically conductive wire pattern. An actuation force generated between the patterned wire structure and an electrode result in closure of a flow channel formed in elastomer material underlying the wire. In one embodiment of a valve structure in accordance with the present invention, the wire structure is patterned by lithography and etching of a copper/polyimide laminate, with an underlying gold plate positioned on the opposite side of the flow channel serving as an electrode. In an alternative embodiment, a first wire structure is patterned by physically cutting out a first pattern of strips from an Aluminum/Mylar(®) laminate sheet. A second patterned wire structure serving as the electrode is formed by the same method, and positioned on the opposite side of a control channel. Application of an actuation force between the first and second patterned strips closes the control channel and an associated flow channel underlying the control channel.

Methods for detecting and sorting polynucleotides based on size

Abstract: This invention relates in general to a method for molecular fingerprinting. The method can be used for forensic identification (e.g. DNA fingerprinting, especially by VNTR), bacterial typing, and human/animal pathogen diagnosis. More particularly, molecules such as polynucleotides (e.g. DNA) can be assessed or sorted by size in a microfabricated device that analyzes the polynucleotides according to restriction fragment length polymorphism. In a microfabricated device according to the invention, DNA fragments or other molecules can be rapidly and accurately typed using relatively small samples, by measuring for example the signal of an optically-detectable (e.g., fluorescent) reporter associated with the polynucleotide fragments.

Velocity independent analyte characterization

Abstract: The present invention provides apparatuses for determining velocity independent analyte characteristic parameters and methods for using the same. In one particular aspect, the present invention provides a velocity independent flow cytometry.