The present invention generally relates to droplet libraries and to systems and methods for the formation of libraries of droplets. The present invention also relates to methods utilizing these droplet libraries in various biological, chemical, or diagnostic assays.

The present invention provides a method of determining integrity and/or quantity of cell free DNA (cfDNA) in a biological sample comprising amplifying target sequences with at least a first primer/probe set and at least a second primer probe/set, amplifying the target sequences of differing lengths, and monitoring for detection of the labels of the oligonucleotide probes, and determining the integrity and/or quantity of the cfDNA based on the level of detection of the label of the oligonucleotide probe from the first primer/probe set compared to the level detection of the label of the oligonucleotide probe from the second primer/probe set. The present invention also provides methods for generating a library with the cfDNA for sequencing and analysis.

The invention relates to a device for synthesising oligonucleotides, comprising: a reagent container receptacle (1) for holding a reagent container support (17) comprising multiple reagent containers (18); an exchangeable microfluid chip (10) comprising a synthesis chamber, fluid connectors and microfluid valves; a control device (5); fluid connecting means (2); wherein the device can be loaded with the microfluid chip (10) and the reagent container support (17) when in a loading position; a chip receptacle (3). To allow cost-effective and prompt synthesis even of small amounts of oligonucleotides, the invention provides for an actuator device (6) to be provided, with which the reagent container receptacle (1), the microfluid chip (10) and the fluid connecting means (2) can be brought from the loading position to an operating position, in which operating position the reagent container receptacle (1), the chip receptacle (3) and the fluid connecting means (2) are positioned relative to each other such that reagents can be conveyed out of the reagent containers (18) towards the synthesis chamber (14) depending on the valve position of the microfluid valves.

Apparatuses and a method for plate-based oligonucleotide synthesis are disclosed. In one example, an apparatus used in oligonucleotide synthesis includes a machined block to receive a commercially-available synthesis plate. A keeper is used to apply pressure to the commercially-available synthesis plate, and a sealing element is used to seal the commercially-available synthesis plate to the machined block. Other methods and apparatuses are disclosed.

Provided herein are compositions, devices, systems and methods for generation and use of biomolecule-based information for storage. Further provided are devices comprising addressable electrodes controlling polynucleotide synthesis (deprotection, extension, or cleavage, etc.) Further provided are compositions for low voltage deprotection of polynucleotides.

An example method includes reacting a first solution and a different, second solution on a flow cell by flowing the first solution over amplification sites on the flow cell and subsequently flowing the second solution over the amplification sites. The first solution includes target nucleic acids and a first reagent mixture that comprises nucleoside triphosphates and replication enzymes. The target nucleic acids in the first solution transport to and bind to the amplification sites at a transport rate. The first reagent mixture amplifies the target nucleic acids that are bound to the amplification sites to produce clonal populations of amplicons originating from corresponding target nucleic acids. The amplicons are produced at an amplification rate that exceeds the transport rate. The second solution includes a second reagent mixture and lacks the target nucleic acids. The second solution is to increase a number of the amplicons at the amplification sites.

In one embodiment, a sample surface of a biosensor includes pixel areas and holds a plurality of clusters during a sequence of sampling events such that the clusters are distributed unevenly over the pixel areas. In another embodiment, a biosensor has a sample surface that includes pixel areas and an array of wells overlying the pixel areas, the biosensor including two wells and two clusters per pixel area. The two wells per pixel area include a dominant well and a subordinate well. The dominant well has a larger cross section over the pixel area than the subordinate well. In yet another embodiment, an illumination system is coupled to a biosensor that illuminates the pixel areas with different angles of illumination during a sequence of sampling events, including, for a sampling event, illuminating each of the wells with off-axis illumination to produce asymmetrically illuminated well regions in each of the wells.

Provided herein are compositions, devices, systems and methods for DNA oligomer synthesis. Further provided are devices comprising addressable electrodes controlling polynucleotide synthesis (deprotection, extension, or cleavage, etc.). The compositions, devices, systems and methods described herein provide improved synthesis, storage, density, and retrieval of biomolecule-based information.

Methods and compositions are disclosed relating to the localization of nucleic acids to arrays such as silane-free arrays, and of sequencing the nucleic acids localized thereby.

Provided is a means capable of determining the development of myocarditis or the risk thereof by a simple and minimally invasive method. A method of determining the development of myocarditis or risk thereof, wherein it is determined that myocarditis is developed or there is a risk thereof when a concentration or expression amount of ADAM28 in a body fluid sample collected from a subject is reduced compared with a reference value.