Microfluidic devices with removable cover and methods of fabrication and application

The present invention includes microfluidic systems having a microfabricated cavity that may be covered with a removable cover, where the removable cover allows at least part of the opening of the microfabricated cavity to be exposed or directly accessed by an operator. The microfluidic systems comprise chambers, flow and control channels formed in elastomeric layers that may comprise PDMS. The removable cover comprises a thermoplastic base film bonded to an elastomer layer by an adhesive layer. When the removable cover is peeled off, the chamber is at least partially open to allow sample extraction from the chamber. The chamber may have macromolecular crystals formed inside or resulting contents from a PCR reaction. The invention also includes a method for making vias in elastomeric layers by using the removable cover. The invention further includes methods and devices for peeling the peelable cover or a removable component such as Integrated Heater Spreader.

INTEGRATED CHIP CARRIERS WITH THERMOCYCLER INTERFACES AND METHODS OF USING THE SAME

Methods and systems are provided for conducting a reaction at a selected temperature or range of temperatures over time. An array device is provided. The array device contains separate reaction chambers and is formed as an elastomeric block from multiple layers. At least one layer has at least one recess that recess has at least one deflectable membrane integral to the layer with the recess. The array device has a thermal transfer device proximal to at least one of the reaction chambers. The thermal transfer device is formed to contact a thermal control source. Reagents for carrying out a desired reaction are introduced into the array device. The array device is contacted with a thermal control device such that the thermal control device is in thermal communication with the thermal control source so that a temperature of the reaction in at least one of the reaction chamber is changed as a result of a change in temperature of the thermal control source.

Integrated chip carriers with thermocycler interfaces and methods of using the same

Methods and systems are provided for conducting a reaction at a selected temperature or range of temperatures over time. An array device is provided. The array device contains separate reaction chambers and is formed as an elastomeric block from multiple layers. At least one layer has at least one recess that recess has at least one deflectable membrane integral to the layer with the recess. The array device has a thermal transfer device proximal to at least one of the reaction chambers. The thermal transfer device is formed to contact a thermal control source. Reagents for carrying out a desired reaction are introduced into the array device. The array device is contacted with a thermal control device such that the thermal control device is in thermal communication with the thermal control source so that a temperature of the reaction in at least one of the reaction chamber is changed as a result of a change in temperature of the thermal control source.

Microfluidic Devices and Methods

Embodiments of the present invention provide improved microfluidic devices and related apparatus, systems, and methods. Methods are provided for reducing mixing times during use of microfluidic devices. Microfluidic devices and related methods of manufacturing are provided with increased manufacturing yield rates. Improved apparatus and related systems are provided for supplying controlled pressure to microfluidic devices. Methods and related microfluidic devices are provided for reducing dehydration of microfluidic devices during use. Microfluidic devices and related methods are provided with improved sample to reagent mixture ratio control. Microfluidic devices and systems are provided with improved resistance to compression fixture pressure induced failures. Methods and systems for conducting temperature controlled reactions using microfluidic devices are provided that reduce condensation levels within the microfluidic device. Methods and systems are provided for improved fluorescent imaging of microfluidic devices. 1providing a microfluidic device having a reaction cell, the reaction cell including a sample chamber having a first volume and a reagent chamber having a second volume, the sample chamber and the reagent chamber being in fluid communication through an interface channel having an interface valve for controlling fluid communication between the sample chamber and the reagent chamber;introducing a sample fluid into the sample chamber so as to pressurize the sample fluid in the sample chamber to a first pressure;introducing a reagent fluid into the reagent chamber so as to pressurize the reagent fluid in the reagent chamber to a second pressure; andmixing sample fluid from the sample chamber with reagent fluid from the reagent chamber by opening the interface valve, wherein the first pressure and the second pressure are sufficiently different to cause the mixing to occur at least in part by fluid injection.. A method for reducing mixing times associated ...

SINGLE-CELL NUCLEIC ACID ANALYSIS

The present invention provides methods for analysis of genomic DNA and/or RNA from small samples or even single cells. Methods for analyzing genomic DNA can entail whole genome amplification (WGA), followed by preamplification and amplification of selected target nucleic acids. Methods for analyzing RNA can entail reverse transcription of the desired RNA, followed by preamplification and amplification of selected target nucleic acids. 1. A method for genotyping a single cell , said method comprising:(a) performing whole genome amplification of the genome of a single cell to produce an amplified genome;(b) preamplifying the amplified genome to produce a preamplification reaction mixture comprising one or more amplicons specific for one or more target nucleic acids; and(c) amplifying and detecting the one or more amplicons.2. A method for analyzing RNA from a single cell , said method comprising:(a) preparing DNA from RNA from a single cell;(b) preamplifying the DNA to produce a preamplification reaction mixture comprising one or more amplicons specific for one or more target nucleic acids; and(c) amplifying and detecting the one or more amplicons.332-. (canceled) This application is a continuation of U.S. non-provisional application Ser. No. 14/102,331, filed Dec. 10, 2013, by Hamilton et al., which is a continuation of U.S. non-provisional application Ser. No. 12/687,018, filed Jan. 13, 2010, which claims the benefit of U.S. provisional application No. 61/144,416, filed Jan. 13, 2009; U.S. provisional application No. 61/146,583, filed Jan. 22, 2009; and U.S. provisional application No. 61/284,309, filed Dec. 15, 2009, all of which applications are hereby incorporated by reference in their entireties.The invention relates to methods useful for analyzing the nucleic acids, e.g., genomic DNA or RNA (e.g., non-coding RNA or mRNA), of small populations of cells or single cells.An obstacle to the rapid and reliable analysis of genomic DNA or RNA (e.g., non-coding RNA or ...

MICROFLUIDIC DEVICES AND METHODS

Embodiments of the present invention provide improved microfluidic devices and related apparatus, systems, and methods. Methods are provided for reducing mixing times during use of microfluidic devices. Microfluidic devices and related methods of manufacturing are provided with increased manufacturing yield rates. Improved apparatus and related systems are provided for supplying controlled pressure to microfluidic devices. Methods and related microfluidic devices are provided for reducing dehydration of microfluidic devices during use. Microfluidic devices and related methods are provided with improved sample to reagent mixture ratio control. Microfluidic devices and systems are provided with improved resistance to compression fixture pressure induced failures. Methods and systems for conducting temperature controlled reactions using microfluidic devices are provided that reduce condensation levels within the microfluidic device. Methods and systems are provided for improved fluorescent ...

Single-cell nucleic acid analysis

The present invention provides methods for analysis of genomic DNA and/or RNA from small samples or even single cells. Methods for analyzing genomic DNA can entail whole genome amplification (WGA), followed by preamplification and amplification of selected target nucleic acids. Methods for analyzing RNA can entail reverse transcription of the desired RNA, followed by preamplification and amplification of selected target nucleic acids.

Microfluidic devices with removable cover and methods of fabrication and application

The present invention includes microfluidic systems having a microfabricated cavity that may be covered with a removable cover, where the removable cover allows at least part of the opening of the microfabricated cavity to be exposed or directly accessed by an operator. The microfluidic systems comprise chambers, flow and control channels formed in elastomeric layers that may comprise PDMS. The removable cover comprises a thermoplastic base film bonded to an elastomer layer by an adhesive layer. When the removable cover is peeled off, the chamber is at least partially open to allow sample extraction from the chamber. The chamber may have macromolecular crystals formed inside or resulting contents from a PCR reaction. The invention also includes a method for making vias in elastomeric layers by using the removable cover. The invention further includes methods and devices for peeling the peelable cover or a removable component such as Integrated Heater Spreader.

Crystal forming devices and systems and methods for using the same

The present invention provides for microfluidic devices and methods for their use. The invention further provides for apparatus and systems for using the microfluidic devices, analyze reactions carried out in the microfluidic devices, and systems to generate, store, organize, and analyze data generated from using the microfluidic devices. The invention further provides methods of using and making microfluidic systems and devices which, in some embodiments, are useful for crystal formation. In one embodiment, an apparatus includes a platen having a platen face with one or more fluid ports therein. The fluid ports spatially correspond to one or more wells on a surface of the microfluidic device. A platform for holding the microfluidic device relative to the platen is included, and a platen actuator for urging the platen against the microfluidic device so that at least one of the fluid ports of the platen is urged against one of the wells to form a pressure chamber comprising the well and the port, so that when pressurized fluid is introduced or removed into or from the pressure chamber through one of the ports, fluid pressure is changed therein.

Integrated Chip Carriers With Thermocycler Interfaces And Methods Of Using The Same

Methods and systems are provided for conducting a reaction at a selected temperature or range of temperatures over time. An array device is provided. The array device contains separate reaction chambers and is formed as an elastomeric block from multiple layers. At least one layer has at least one recess that recess has at least one deflectable membrane integral to the layer with the recess. The array device has a thermal transfer device proximal to at least one of the reaction chambers. The thermal transfer device is formed to contact a thermal control source. Reagents for carrying out a desired reaction are introduced into the array device. The array device is contacted with a thermal control device such that the thermal control device is in thermal communication with the thermal control source so that a temperature of the reaction in at least one of the reaction chamber is changed as a result of a change in temperature of the thermal control source.

Integrated chip carriers with thermocycler interfaces and methods of using the same

Methods and systems are provided for conducting a reaction at a selected temperature or range of temperatures over time. An array device is provided. The array device contains separate reaction chambers and is formed as an elastomeric block from multiple layers. At least one layer has at least one recess that recess has at least one deflectable membrane integral to the layer with the recess. The array device has a thermal transfer device proximal to at least one of the reaction chambers. The thermal transfer device is formed to contact a thermal control source. Reagents for carrying out a desired reaction are introduced into the array device. The array device is contacted with a thermal control device such that the thermal control device is in thermal communication with the thermal control source so that a temperature of the reaction in at least one of the reaction chamber is changed as a result of a change in temperature of the thermal control source.

SINGLE-CELL NUCLEIC ACID ANALYSIS

The present invention provides methods for analysis of genomic DNA and/or RNA from small samples or even single cells. Methods for analyzing genomic DNA can entail whole genome amplification (WGA), followed by preamplification and amplification of selected target nucleic acids. Methods for analyzing RNA can entail reverse transcription of the desired RNA, followed by preamplification and amplification of selected target nucleic acids.

Integrated chip carriers with thermocycler interfaces and methods of using the same

Methods and systems are provided for conducting a reaction at a selected temperature or range of temperatures over time. An array device is provided. The array device contains separate reaction chambers and is formed as an elastomeric block from multiple layers. At least one layer has at least one recess that recess has at least one deflectable membrane integral to the layer with the recess. The array device has a thermal transfer device proximal to at least one of the reaction chambers. The thermal transfer device is formed to contact a thermal control source. Reagents for carrying out a desired reaction are introduced into the array device. The array device is contacted with a thermal control device such that the thermal control device is in thermal communication with the thermal control source so that a temperature of the reaction in at least one of the reaction chamber is changed as a result of a change in temperature of the thermal control source.

Microfluidic Devices With Removable Cover and Methods of Fabrication and Application

The present invention includes microfluidic systems having a microfabricated cavity that may be covered with a removable cover, where the removable cover allows at least part of the opening of the microfabricated cavity to be exposed or directly accessed by an operator. The microfluidic systems comprise chambers, flow and control channels formed in elastomeric layers that may comprise PDMS. The removable cover comprises a thermoplastic base film bonded to an elastomer layer by an adhesive layer. When the removable cover is peeled off, the chamber is at least partially open to allow sample extraction from the chamber. The chamber may have macromolecular crystals formed inside or resulting contents from a PCR reaction. The invention also includes a method for making vias in elastomeric layers by using the removable cover. The invention further includes methods and devices for peeling the peelable cover or a removable component such as Integrated Heater Spreader.

Microfluidic devices and methods

Embodiments of the present invention provide improved microfluidic devices and related apparatus, systems, and methods. Methods are provided for reducing mixing times during use of microfluidic devices. Microfluidic devices and related methods of manufacturing are provided with increased manufacturing yield rates. Improved apparatus and related systems are provided for supplying controlled pressure to microfluidic devices. Methods and related microfluidic devices are provided for reducing dehydration of microfluidic devices during use. Microfluidic devices and related methods are provided with improved sample to reagent mixture ratio control. Microfluidic devices and systems are provided with improved resistance to compression fixture pressure induced failures. Methods and systems for conducting temperature controlled reactions using microfluidic devices are provided that reduce condensation levels within the microfluidic device. Methods and systems are provided for improved fluorescent imaging of microfluidic devices.

MICROFLUIDIC DEVICES WITH REMOVABLE COVER AND METHODS OF FABRICATION AND APPLICATION

The present invention includes microfluidic systems having a microfabricated cavity that may be covered with a removable cover, where the removable cover allows at least part of the opening of the microfabricated cavity to be exposed or directly accessed by an operator. The microfluidic systems comprise chambers, flow and control channels formed in elastomeric layers that may comprise PDMS. The removable cover comprises a thermoplastic base film bonded to an elastomer layer by an adhesive layer. When the removable cover is peeled off, the chamber is at least partially open to allow sample extraction from the chamber. The chamber may have macromolecular crystals formed inside or resulting contents from a PCR reaction. The invention also includes a method for making vias in elastomeric layers by using the removable cover. The invention further includes methods and devices for peeling the peelable cover or a removable component such as Integrated Heater Spreader. 1. A microfluidic system comprising:a base substrate;a sample holding layer formed on the base substrate, wherein the sample holding layer comprises a microfabricated cavity or recess having an opening formed on a surface of the layer that faces opposite the substrate;a flow channel coupled to the cavity for delivering a reagent to the cavity;a control channel that intersects the flow channel and forms a deflectable membrane over at least a portion of the intersection, wherein actuation of the control channel causes deflection of the deflectable membrane to open or close the flow channel; anda removable cover bonded to the sample holding layer, wherein the cover is removable to expose at least part of the opening in the microfabricated cavity.2. The microfluidic system of claim 1 , wherein the sample holding layer comprises an elastomeric material.3. The microfluidic system of claim 1 , wherein the sample holding layer comprises a non-elastomeric material.4. The microfluidic system of claim 1 , wherein the non ...

ASSAYS FOR THE DETECTION OF GENOTYPE, MUTATIONS, AND/OR ANEUPLOIDY

The present invention provides amplification-based methods for detection of genotype, mutations, and/or aneuploidy. These methods have broad applicability, but are particularly well-suited to detecting and quantifying target nucleic acids in free fetal DNA present in a maternal bodily fluid sample. 1. A method for detecting and/or quantifying one or more target amplicons produced by amplification , wherein the detecting and/or quantifying is carried out during amplification or after an amplification endpoint has been reached , the method comprising: sample nucleic acids;', 'at least one target-specific primer pair;', 'an optional probe, wherein at least one primer of the target-specific primer pair or the probe, if present, is labeled with a fluorescent dye; and', 'a fluorescent double-stranded DNA-binding dye, where fluorescence from the dye is capable of quenching fluorescent signal from the labeled primer or probe, if present;, 'preparing an amplification reaction mixture comprisingsubjecting the amplification mixture to amplification; anddetecting fluorescent signal to detect and/or quantify the one or more target amplicons.2. A method for detecting and/or quantifying one or more target amplicons produced by amplification , wherein the detecting and/or quantifying is carried out during amplification or after an amplification endpoint has been reached , the method comprising: sample nucleic acids;', 'at least one target-specific primer pair, wherein at least one primer in the target-specific primer pair comprises a nucleotide tag at the 5′ end of the primer;', 'at least one fluorescently labeled primer or probe that is capable of annealing to the nucleotide tag, directly or via one or more intervening primers, whereby the label can become linked to the nucleotide tag; and', 'a fluorescent double-stranded DNA-binding dye, where fluorescence from the dye is capable of quenching fluorescent signal from the labeled primer or probe;, 'preparing an amplification ...

INTEGRATED CHIP CARRIERS WITH THERMOCYCLER INTERFACES AND METHODS OF USING THE SAME

Methods and systems are provided for conducting a reaction at a selected temperature or range of temperatures over time. An array device is provided. The array device contains separate reaction chambers and is formed as an elastomeric block from multiple layers. At least one layer has at least one recess that recess has at least one deflectable membrane integral to the layer with the recess. The array device has a thermal transfer device proximal to at least one of the reaction chambers. The thermal transfer device is formed to contact a thermal control source. Reagents for carrying out a desired reaction are introduced into the array device. The array device is contacted with a thermal control device such that the thermal control device is in thermal communication with the thermal control source so that a temperature of the reaction in at least one of the reaction chamber is changed as a result of a change in temperature of the thermal control source.

Integrated chip carriers with thermocycler interfaces and methods of using the same

Methods and systems are provided for conducting a reaction at a selected temperature or range of temperatures over time. An array device is provided. The array device contains separate reaction chambers and is formed as an elastomeric block from multiple layers. At least one layer has at least one recess that recess has at least one deflectable membrane integral to the layer with the recess. The array device has a thermal transfer device proximal to at least one of the reaction chambers. The thermal transfer device is formed to contact a thermal control source. Reagents for carrying out a desired reaction are introduced into the array device. The array device is contacted with a thermal control device such that the thermal control device is in thermal communication with the thermal control source so that a temperature of the reaction in at least one of the reaction chamber is changed as a result of a change in temperature of the thermal control source.

Single cell nucleic acid analysis

The present invention provides methods for analysis of genomic DNA and/or RNA from small samples or even single cells. Methods for analyzing genomic DNA can entail whole genome amplification (WGA), followed by preamplification and amplification of selected target nucleic acids. Methods for analyzing RNA can entail reverse transcription of the desired RNA, followed by preamplification and amplification of selected target nucleic acids.

Integrated chip carriers with thermocycler interfaces and methods of using the same

Methods and systems are provided for conducting a reaction at a selected temperature or range of temperatures over time. An array device is provided. The array device contains separate reaction chambers and is formed as an elastomeric block from multiple layers. At least one layer has at least one recess that recess has at least one deflectable membrane integral to the layer with the recess. The array device has a thermal transfer device proximal to at least one of the reaction chambers. The thermal transfer device is formed to contact a thermal control source. Reagents for carrying out a desired reaction are introduced into the array device. The array device is contacted with a thermal control device such that the thermal control device is in thermal communication with the thermal control source so that a temperature of the reaction in at least one of the reaction chamber is changed as a result of a change in temperature of the thermal control source.

Single cell nucleic acid analysis

The present invention provides methods for analysis of genomic DNA and/or RNA from small samples or even single cells. Methods for analyzing genomic DNA can entail whole genome amplification (WGA), followed by preamplification and amplification of selected target nucleic acids. Methods for analyzing RNA can entail reverse transcription of the desired RNA, followed by preamplification and amplification of selected target nucleic acids.

Crystal forming devices and systems and methods for using the same

The present invention provides for microfluidic devices and methods for their use. The invention further provides for apparatus and systems for using the microfluidic devices, analyze reactions carried out in the microfluidic devices, and systems to generate, store, organize, and analyze data generated from using the microfluidic devices. The invention further provides methods of using and making microfluidic systems and devices which, in some embodiments, are useful for crystal formation. In one embodiment, an apparatus includes a platen having a platen face with one or more fluid ports therein. The fluid ports spatially correspond to one or more wells on a surface of the microfluidic device. A platform for holding the microfluidic device relative to the platen is included, and a platen actuator for urging the platen against the microfluidic device so that at least one of the fluid ports of the platen is urged against one of the wells to form a pressure chamber comprising the well and the port, so that when pressurized fluid is introduced or removed into or from the pressure chamber through one of the ports, fluid pressure is changed therein.

Microfluidic devices and methods

Embodiments of the present invention provide improved microfluidic devices and related apparatus, systems, and methods. Methods are provided for reducing mixing times during use of microfluidic devices. Microfluidic devices and related methods of manufacturing are provided with increased manufacturing yield rates. Improved apparatus and related systems are provided for supplying controlled pressure to microfluidic devices. Methods and related microfluidic devices are provided for reducing dehydration of microfluidic devices during use. Microfluidic devices and related methods are provided with improved sample to reagent mixture ratio control. Microfluidic devices and systems are provided with improved resistance to compression fixture pressure induced failures. Methods and systems for conducting temperature controlled reactions using microfluidic devices are provided that reduce condensation levels within the microfluidic device. Methods and systems are provided for improved fluorescent imaging of microfluidic devices.

Microfluidic devices and methods

Embodiments of the present invention provide improved microfluidic devices and related apparatus, systems, and methods. Methods are provided for reducing mixing times during use of microfluidic devices. Microfluidic devices and related methods of manufacturing are provided with increased manufacturing yield rates. Improved apparatus and related systems are provided for supplying controlled pressure to microfluidic devices. Methods and related microfluidic devices are provided for reducing dehydration of microfluidic devices during use. Microfluidic devices and related methods are provided with improved sample to reagent mixture ratio control. Microfluidic devices and systems are provided with improved resistance to compression fixture pressure induced failures. Methods and systems for conducting temperature controlled reactions using microfluidic devices are provided that reduce condensation levels within the microfluidic device. Methods and systems are provided for improved fluorescent imaging of microfluidic devices.

SINGLE-CELL NUCLEIC ACID ANALYSIS

The present invention provides methods for analysis of genomic DNA and/or RNA from small samples or even single cells. Methods for analyzing genomic DNA can entail whole genome amplification (WGA), followed by preamplification and amplification of selected target nucleic acids. Methods for analyzing RNA can entail reverse transcription of the desired RNA, followed by preamplification and amplification of selected target nucleic acids. 1. A method for analyzing DNA from a single cell , said method comprising:(a) performing whole genome amplification of the genome of a single cell to produce an amplified genome, wherein the method entails performing whole genome amplification for fewer than, or about, 10 amplification cycles;(b) preamplifying the amplified genome using a plurality of target-specific primer pairs to produce a preamplification reaction mixture comprising a plurality of amplicons specific for a plurality of target nucleic acids;(c) distributing the plurality of amplicons within a device; and(d) amplifying and detecting the plurality of amplicons in the device.2. A method for analyzing mRNA from a single cell , said method comprising:(a) preparing DNA from the mRNA of a single cell;(b) preamplifying the DNA using a plurality of target-specific primer pairs to produce a preamplification reaction mixture comprising a plurality of amplicons specific for a plurality of target nucleic acids, wherein said preamplification is carried out for 18 amplification cycles or fewer;(c) distributing the plurality of amplicons within a device; and(d) amplifying and detecting the plurality of amplicons in the device.33335. The method of any of , , or - , wherein said single cell comprises a mammalian cell.4. The method of claim 3 , wherein said single cell is selected from a cell from a preimplantation embryo claim 3 , a stem cell claim 3 , a suspected cancer cell claim 3 , a cell from a pathogenic organism claim 3 , and a cell obtained from a crime scene.5. The method of ...

MICROFLUIDIC DEVICES AND METHODS

Embodiments of the present invention provide improved microfluidic devices and related apparatus, systems, and methods. Methods are provided for reducing mixing times during use of microfluidic devices. Microfluidic devices and related methods of manufacturing are provided with increased manufacturing yield rates. Improved apparatus and related systems are provided for supplying controlled pressure to microfluidic devices. Methods and related microfluidic devices are provided for reducing dehydration of microfluidic devices during use. Microfluidic devices and related methods are provided with improved sample to reagent mixture ratio control. Microfluidic devices and systems are provided with improved resistance to compression fixture pressure induced failures. Methods and systems for conducting temperature controlled reactions using microfluidic devices are provided that reduce condensation levels within the microfluidic device. Methods and systems are provided for improved fluorescent ...

Microfluidic Devices and Methods

Embodiments of the present invention provide improved microfluidic devices and related apparatus, systems, and methods. Methods are provided for reducing mixing times during use of microfluidic devices. Microfluidic devices and related methods of manufacturing are provided with increased manufacturing yield rates. Improved apparatus and related systems are provided for supplying controlled pressure to microfluidic devices. Methods and related microfluidic devices are provided for reducing dehydration of microfluidic devices during use. Microfluidic devices and related methods are provided with improved sample to reagent mixture ratio control. Microfluidic devices and systems are provided with improved resistance to compression fixture pressure induced failures. Methods and systems for conducting temperature controlled reactions using microfluidic devices are provided that reduce condensation levels within the microfluidic device. Methods and systems are provided for improved fluorescent imaging of microfluidic devices. 1providing a microfluidic device having a reaction cell, the reaction cell including a sample chamber having a first volume and a reagent chamber having a second volume, the sample chamber and the reagent chamber being in fluid communication through an interface channel having an interface valve for controlling fluid communication between the sample chamber and the reagent chamber;introducing a sample fluid into the sample chamber so as to pressurize the sample fluid in the sample chamber to a first pressure;introducing a reagent fluid into the reagent chamber so as to pressurize the reagent fluid in the reagent chamber to a second pressure; andmixing sample fluid from the sample chamber with reagent fluid from the reagent chamber by opening the interface valve, wherein the first pressure and the second pressure are sufficiently different to cause the mixing to occur at least in part by fluid injection.. A method for reducing mixing times associated ...

Thermal reaction device and method for using the same

An M x N matrix microfluidic device for performing a matrix of reactions, the device (100) having a plurality of reaction cells (106) in communication with one of either a sample inlet (120) or a reagent t inlet (124) through a via formed within an elastomeric block of the device. Methods provided include a method for forming vias in parallel in an elastomeric layer of an elastomeric block of a microfluidic device, the method includes using patterned photoresist masks and etching reagents to etch away regions or portions of an elastomeric layer of the elastomeric block.

Assays for the detection of genotype, mutations, and/or aneuploidy

Thermal reaction device and method for using the same

An M x N matrix microfluidic device for performing a matrix of reactions, the device (100) having a plurality of reaction cells (106) in communication with one of either a sample inlet (120) or a reagent t inlet (124) through a via formed within an elastomeric block of the device. Methods provided include a method for forming vias in parallel in an elastomeric layer of an elastomeric block of a microfluidic device, the method includes using patterned photoresist masks and etching reagents to etch away regions or portions of an elastomeric layer of the elastomeric block. Fig. 1A

Thermal reaction device and method for using the same

Thermal reaction device and method for using the same

Microfluidic devices with removable cover and methods of fabrication and application

The present invention includes microfluidic systems having a microfabricated cavity that may be covered with a removable cover, where the removable cover allows at least part of the opening of the microfabricated cavity to be exposed or directly accessed by an operator. The microfluidic systems comprise chambers, flow and control channels formed in elastomeric layers that may comprise PDMS. The removable cover comprises a thermoplastic base film bonded to an elastomer layer by an adhesive layer. When the removable cover is peeled off, the chamber is at least partially open to allow sample extraction from the chamber. The chamber may have macromolecular crystals formed inside or resulting contents from a PCR reaction. The invention also includes a method for making vias in elastomeric layers by using the removable cover. The invention further includes methods and devices for peeling the peelable cover or a removable component such as Integrated Heater Spreader. Fig. 1B

Crystal forming devices and systems and methods for making and using the same

Crystal forming devices and systems and methods for making and using the same

The present invention provides for microfluidic devices and methods for their use. The invention further provides for apparatus and systems for using the microfluidic devices, analyze reactions carried out in the microfluidic devices, and systems to generate, store, organize, and analyze data generated from using the microfluidic devices. The invention further provides methods of using and making microfluidic systems and devices which, in some embodiments, are useful for crystal formation. In one embodiment, an apparatus includes a platen having a platen face with one or more fluid ports therein. The fluid ports spatially correspond to one or more wells on a surface of the microfluidic device. A platform for holding the microfluidic device relative to the platen is included, and a platen actuator for urging the platen against the microfluidic device so that at least one of the fluid ports of the platen is urged against one of the wells to form a pressure chamber comprising the well and the port, so that when pressurized fluid is introduced or removed into or from the pressure chamber through one of the ports, fluid pressure is changed therein.

Weather resistant, concealable, security storage device

The present invention relates generally devices and methods for the convenient and concealable storage of radio frequency transmitting devices including vehicle smart keys and fobs in close proximity to their target receiver without risk of activation of the target receiver. Also provided are devices for, and methods of attachment of. the devices to a vehicle.

Assays for the detection of genotype, mutations, and/or aneuploidy

The present invention provides amplification-based methods for detection of genotype, mutations, and/or aneuploidy. These methods have broad applicability, but are particularly well-suited to detecting and quantifying target nucleic acids in free fetal DNA present in a maternal bodily fluid sample.

Single-cell nucleic acid analysis

SINGLE-CELL NUCLEIC ACID ANALYSISThe present invention provides methods for analysis of genomic DNA and/or RNA from small samples or even single cells. Methods for analyzing genomic DNA can entail whole genome amplification (WGA), followed by preamplification and amplification of selected target nucleic acids. Methods for analyzing RNA can entail reverse transcription of the desired RNA, followed by preamplification and amplification of selected target nucleic acids.Fig. 1

Assays for the detection of genotype, mutations, and/or aneuploidy

The present invention provides amplification-based methods for detection of genotype, mutations, and/or aneuploidy. These methods have broad applicability, but are particularly well-suited to detecting and quantifying target nucleic acids in free fetal DNA present in a maternal bodily fluid sample.

Microfluidic devices with removable cover and methods of fabrication and application

The present invention includes microfluidic systems having a microfabricated cavity that may be covered with a removable cover, where the removable cover allows at least part of the opening of the microfabricated cavity to be exposed or directly accessed by an operator. The microfluidic systems comprise chambers, flow and control channels formed in elastomeric layers that may comprise PDMS. The removable cover comprises a thermoplastic base film bonded to an elastomer layer by an adhesive layer. When the removable cover is peeled off, the chamber is at least partially open to allow sample extraction from the chamber. The chamber may have macromolecular crystals formed inside or resulting contents from a PCR reaction. The invention also includes a method for making vias in elastomeric layers by using the removable cover. The invention further includes methods and devices for peeling the peelable cover or a removable component such as Integrated Heater Spreader.