Embodiments disclosed herein are directed to microfluidic devices that allow for scalable on-chip screening of combinatorial libraries and methods of use thereof. Droplets comprising individual molecular species to be screened are loaded onto the microfluidic device. The droplets are labeled by methods known in the art, including but not limited to barcoding, such that the molecular species in each droplet can be uniquely identified. The device randomly sorts the droplets into individual microwells of an array of microwells designed to hold a certain number of individual droplets in order to derive combinations of the various molecular species. The paired droplets are then merged in parallel to form merged droplets in each microwell, thereby avoiding issues associated with single stream merging. Each microwell is then scanned, e.g., using microscopy, such as high content imaging microscopy, to detect the optical labels, thereby identifying the combination of molecular species in each microwell.

A reactor system for conducting multiple continuous reactions in parallel may include a preheating unit that includes an outer preheater shell and a plurality of heating tubes disposed within the preheating shell and arranged in parallel. The reactor system may include a reactor unit downstream of the preheating unit, the reactor unit comprising a plurality of reactor tubes disposed within a reactor shell and an outer heating element disposed about the reactor shell. An inlet end of at least one of the reactor tubes may be fluidly coupled to at least one of the heating tubes of the preheating unit. The reactor unit may include a multi-chamber separator downstream of the reactor unit, the multi-chamber separator having a plurality of separation chambers. At least one of the separation chambers may be fluidly coupled to at least one of the reactor tubes.

The invention generally relates to methods for quantifying an amount of enzyme molecules. Systems and methods of the invention are provided for measuring an amount of target by forming a plurality of fluid partitions, a subset of which include the target, performing an enzyme-catalyzed reaction in the subset, and detecting the number of partitions in the subset. The amount of target can be determined based on the detected number.

A microreactor array platform and method for sealing a reagent in microreactors of an array of microreactors are provided. The microreactor array platform includes an array of microreactors, and a sealing film having a first surface and an opposite second surface, the sealing film configured to movably seal the array of microreactors. The microreactor array platform also includes an injector for delivering a reagent into the array of microreactors via a fluid path between the array and the second surface of the sealing film, and an applicator for directing a sealing liquid against the first surface of the sealing film. The microreactor array platform further includes a system for creating a pressure differential between the reagent in the injector and a space between the array of microreactors and the second surface of the sealing film.

The present invention provides improved automated systems and methods for synthesis of biopolymers including DNA and RNA. The automated systems and methods represent a number of improvements over existing systems for multiplex synthesis of biopolymers in a combinatorial fashion.

A flow cell package includes first and second surface-modified patterned wafers and a spacer layer. The first surface-modified patterned wafer includes first depressions separated by first interstitial regions, a first functionalized molecule bound to a first silane or silane derivative in at least some of the first depressions, and a first primer grafted to the first functionalized molecule in the at least some of the first depressions. The second surface-modified patterned wafer includes second depressions separated by second interstitial regions, a second functionalized molecule bound to a second silane or silane derivative in at least some of the second depressions, and a second primer grafted to the second functionalized molecule in the at least some of the second depressions. The spacer layer bonds at least some first interstitial regions to at least some second interstitial regions, and at least partially defines respective fluidic chambers of the flow cell package.

An optical imaging system (100) includes a frame (102) designed to provide mechanical coupling between a first stage (104) and a second stage (106), a sample holding region (108) located on the first stage (104), a lens arrangement, and a sensor array. The lens arrangement is disposed between the first stage (104) and the second stage (106) and is designed to receive light from a sample at the sample holding region (108) on the first stage. The lens arrangement has a numerical aperture less than 0.1. The sensor array is coupled to the second stage (106) and is designed to receive light passing through the lens arrangement.

A flow cell package includes first and second surface-modified patterned wafers and a spacer layer. The first surface-modified patterned wafer includes first depressions separated by first interstitial regions, a first functionalized molecule bound to a first silane or silane derivative in at least some of the first depressions, and a first primer grafted to the first functionalized molecule in the at least some of the first depressions. The second surface-modified patterned wafer includes second depressions separated by second interstitial regions, a second functionalized molecule bound to a second silane or silane derivative in at least some of the second depressions, and a second primer grafted to the second functionalized molecule in the at least some of the second depressions. The spacer layer bonds at least some first interstitial regions to at least some second interstitial regions, and at least partially defines respective fluidic chambers of the flow cell package.

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.

Reagents and solvents used for polymer synthesis are reused or recycled rather than discarded. The outflow from each step of polymer synthesis may be collected separately in one of multiple dedicated containers. Reuse returns the outflow from a step of polymer synthesis back to an input of a polymer synthesizer for subsequent use in that same step. Recycling processes the outflow from one or more steps of polymer synthesis to restore original concentrations or purity levels for use in a later synthesis run. Quality control analysis may determine if outflow collected from a polymer synthesizer is reused or recycled. These techniques reduce reagent cost and waste quantity. These techniques may be used with phosphoramidite or enzyme-based synthesis of deoxyribonucleic acid (DNA).