The present disclosure provides materials and methods for co-determining the cellular location and nucleotide sequence of a DNA that is contacted by (or in close proximity to) a protein of interest in a single cell. Thus the present disclosure provides methods and materials wherein the cellular location of the DNA comprising a DNA-binding site or otherwise in close proximity to a protein of interest is coupled to the sequence of said DNA to provide contemporaneous imaging and sequence measurement of a protein-DNA interaction.

The present disclosure provides materials and methods for co-determining the cellular location and nucleotide sequence of a DNA that is contacted by (or in close proximity to) a protein of interest in a single cell. Thus the present disclosure provides methods and materials wherein the cellular location of the DNA comprising a DNA-binding site or otherwise in close proximity to a protein of interest is coupled to the sequence of said DNA to provide contemporaneous imaging and sequence measurement of a protein-DNA interaction.

The present disclosure generally relates to systems and methods for detecting viruses, e.g., using microfluidic devices. Certain embodiments are generally directed to systems and methods that are able to detect pathogens such as viruses or bacteria by encapsulating a sample in droplets, and applying amplification reagents to the droplets able to amplify nucleic acids therein, e.g., using loop mediated isothermal amplification (LAMP) or other amplification techniques. In addition, some aspects are generally directed to identifying a species in a sample, e.g., at very low concentrations. In some cases, the sample may be broken into droplets, arid the droplets determined to determine the species.

The present disclosure generally relates to systems and methods for detecting viruses, e.g., using microfluidic devices. Certain embodiments are generally directed to systems and methods that are able to detect pathogens such as viruses or bacteria by encapsulating a sample in droplets, and applying amplification reagents to the droplets able to amplify nucleic acids therein, e.g., using loop mediated isothermal amplification (LAMP) or other amplification techniques. In addition, some aspects are generally directed to identifying a species in a sample, e.g., at very low concentrations. In some cases, the sample may be broken into droplets, arid the droplets determined to determine the species.

The present methods are exemplified by a process in which maternal blood containing fetal DNA is diluted to a nominal value of approximately 0.5 genome equivalent of DNA per reaction sample. Digital analysis is then be used to detect aneuploidy, such as the trisomy that causes Down Syndrome. Since aneuploidies do not present a mutational change in sequence, and are merely a change in the number of chromosomes, it has not been possible to detect them in a fetus without resorting to invasive techniques such as amniocentesis or chorionic villi sampling. Digital amplification allows the detection of aneuploidy using massively parallel amplification and detection methods, examining, e.g., 10,000 genome equivalents.

The present methods are exemplified by a process in which maternal blood containing fetal DNA is diluted to a nominal value of approximately 0.5 genome equivalent of DNA per reaction sample. Digital analysis is then be used to detect aneuploidy, such as the trisomy that causes Down Syndrome. Since aneuploidies do not present a mutational change in sequence, and are merely a change in the number of chromosomes, it has not been possible to detect them in a fetus without resorting to invasive techniques such as amniocentesis or chorionic villi sampling. Digital amplification allows the detection of aneuploidy using massively parallel amplification and detection methods, examining, e.g., 10,000 genome equivalents.

Devices and methods for de novo synthesis of large and highly accurate libraries of oligonucleic acids are provided herein. Devices include structures having a main channel and microchannels, where the microchannels have a high surface area to volume ratio. Devices disclosed herein provide for de novo synthesis of oligonucleic acids having a low error rate.

Devices and methods for de novo synthesis of large and highly accurate libraries of oligonucleic acids are provided herein. Devices include structures having a main channel and microchannels, where the microchannels have a high surface area to volume ratio. Devices disclosed herein provide for de novo synthesis of oligonucleic acids having a low error rate.

Systems, methods, and apparatuses are provided for self-contained nucleic acid preparation, amplification, and analysis.

Systems, methods, and apparatuses are provided for self-contained nucleic acid preparation, amplification, and analysis.