High-throughput methods for screening large populations of variant proteins are provided. The methods utilize large-scale arrays of microcapillaries, where each microcapillary comprises a solution containing a variant protein, an immobilized target molecule, and a reporter element. Immobilized target molecules may include any molecule of interest, including proteins, nucleic acids, carbohydrates, and other biomolecules. The association of a variant protein with a molecular target is assessed by measuring a signal from the reporter element. The contents of microcapillaries identified in the assays as containing variant proteins of interest can be isolated, and cells expressing the variant proteins of interest can be characterized. Also provided are systems for performing the disclosed screening methods.

Multi-stage sample-recovery systems, including automated 2-stage and 3-stage sample-recovery systems, are provided. Such systems enable the rapid screening and recovery of samples, including viable cell-based samples, from high-throughput screening systems, including systems utilizing large-scale arrays of microcapillaries. In specific screening systems, each microcapillary comprises a solution containing a variant protein, an immobilized target molecule, and a reporter element. Immobilized target molecules may include any molecule of interest, including proteins, nucleic acids, carbohydrates, and other biomolecules. The association of a variant protein with a molecular target is assessed by measuring a signal from the reporter element. The contents of microcapillaries identified in the assays as containing variant proteins of interest can be identified and recovered using the multi-stage systems disclosed herein.

There is provided a method of charging an array of micro-capillaries. The micro-capillaries have at least one end that is open for fluid communication. The method includes the steps of: (a) filling the array of micro-capillaries with an assay liquid; (b) controllably evaporating at least some of the assay liquid to remove it from the micro-capillary and create a void space in each of the capillaries between the assay liquid and the open end; and (c) filling the void space with a liquid that is immiscible with said assay liquid. There is also provided a use of the disclosed method and a device for charging an array of micro-capillaries.

Provided herein is generally tubular container, preferably including a plurality of reservoirs defined therein. The container can be adapted for acoustic ejection of a fluid disposed within at least one of the reservoirs of the plurality of reservoirs. Alternatively, the container can be adapted for extraction of a fluid disposed within at least one of the reservoirs of the plurality of reservoirs using a non-acoustic liquid handling method.

High-throughput methods for screening large populations of variant proteins are provided. The methods utilize large-scale arrays of microcapillaries, where each microcapillary comprises a solution containing a variant protein, an immobilized target molecule, and a reporter element. Immobilized target molecules may include any molecule of interest, including proteins, nucleic acids, carbohydrates, and other biomolecules. The association of a variant protein with a molecular target is assessed by measuring a signal from the reporter element. The contents of microcapillaries identified in the assays as containing variant proteins of interest can be isolated, and cells expressing the variant proteins of interest can be characterized. Also provided are systems for performing the disclosed screening methods.

High-throughput methods for screening large populations of variant proteins are provided. The methods utilize large-scale arrays of microcapillaries, where each microcapillary comprises a solution containing a variant protein, an immobilized target molecule, and a reporter element. Immobilized target molecules may include any molecule of interest, including proteins, nucleic acids, carbohydrates, and other biomolecules. The association of a variant protein with a molecular target is assessed by measuring a signal from the reporter element. The contents of microcapillaries identified in the assays as containing variant proteins of interest can be isolated, and cells expressing the variant proteins of interest can be characterized. Also provided are systems for performing the disclosed screening methods.

The present invention provides methods, systems, assemblies, and articles for capturing single cells with a polymer capture film. In certain embodiments, the polymer capture films comprise a plurality of individual channels with top and bottom openings, where the channels are dimensioned such that a single cell is: i) is captured inside the channel, partially or substantially occluding the channel, when negative pressure is provided to the bottom opening; or ii) is captured by the top opening, but does not enter the channel, when negative pressure is provided to the bottom opening. In some embodiments, the channels of the polymer capture film align with the wells of a multi-well chip such that the cell, or the contents of the single cell, may be transferred to a corresponding well.

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.

The invention features methods of making devices, or platens, having a high-density array of through-holes, as well as methods of cleaning and refurbishing the surfaces of the platens. The invention further features methods of making high-density arrays of chemical, biochemical, and biological compounds, having many advantages over conventional, lower-density arrays. The invention includes methods by which many physical, chemical or biological transformations can be implemented in serial or in parallel within each addressable through-hole of the devices. Additionally, the invention includes methods of analyzing the contents of the array, including assaying of physical properties of the samples.

A flowcell for a sequencing instrument. The flowcell includes a fluid inlet, a fluid outlet, a flow channel formed between an at least partially transparent cover and a base and fluidly connecting the fluid inlet to the fluid outlet, and a capture substrate provided in the flow channel. The capture substrate includes microretainers configured to each receive a single microspot having a microspot diameter, and microretainer is separated from adjacent microretainers by an interstitial gap distance that is equal to or greater than the microspot diameter. A particle separator may be fluidly connected to the flowcell. The particle separator may include a microfluidic channel having an array of micropillars to transfer a plurality of the microspots to a loading buffer that may be delivered to the flowcell.