In an illustrative embodiment, automated multi-module cell editing instruments are provided to automate multiple edits into nucleic acid sequences inside one or more cells.

The present disclosure provides a HTP microbial genomic engineering platform that is computationally driven and integrates molecular biology, automation, and advanced machine learning protocols. This integrative platform utilizes a suite of HTP molecular tool sets to create HTP genetic design libraries, which are derived from, inter alia, scientific insight and iterative pattern recognition. The HTP genomic engineering platform described herein is microbial strain host agnostic and therefore can be implemented across taxa. Furthermore, the disclosed platform can be implemented to modulate or improve any microbial host parameter of interest.

A method of controlling a needle actuator to interact with a cell is provided, the method comprising: providing an actuator comprising a tower, a stage and a needle, wherein the needle is mounted on the stage; applying an electrostatic potential between the tower and the stage to retract the needle; moving the actuator towards the cell; reducing the potential so as to allow the stage and needle to move towards the cell; applying calibration data to detect when the needle has pierced the cell; and reducing the potential further once it has been detected that the needle has pierced the cell. The cell can be a biological cell. The needle can be a micro-needle and the stage can be a micro-stage.

The present disclosure provides a HTP microbial genomic engineering platform that is computationally driven and integrates molecular biology, automation, and advanced machine learning protocols. This integrative platform utilizes a suite of HTP molecular tool sets to create HTP genetic design libraries, which are derived from, inter alia, scientific insight and iterative pattern recognition. The HTP genomic engineering platform described herein is microbial strain host agnostic and therefore can be implemented across taxa. Furthermore, the disclosed platform can be implemented to modulate or improve any microbial host parameter of interest.

In an illustrative embodiment, automated multi-module cell editing instruments are provided to automate multiple edits into nucleic acid sequences inside one or more cells.

A 3D-printed in vitro model biological microenvironment in examples discussed below may have one or more of the following features: (a) a gel matrix 3D-printed scaffold, wherein the gel matrix comprises a chemical composition configured to culture a first type of live cells, (b) a target chemical disposed at one or more locations within the gel matrix, the target chemical forming a chemical depot from which a chemical gradient is created within the gel matrix, (c) a conduit disposed within the gel matrix and defining a lumen comprising a second type of live cells, wherein the conduit is configured to enable at least some of the first type of live cells to migrate through the conduit and facilitate flow of at least: some of the live cells to an outlet of the conduit, or enable introduction of at least one of other cells, Achemical mediators, or drugs into the 3D-printed microenvironment.

Disclosed herein are apparatus and methods to perform in-vitro probing of cell interior using a nanoneedle. Some aspects of the present application relate to an apparatus with a vertical nanoneedle disposed in a flow channel, wherein the flow channel is shaped to facilitate immobilization of a cell recirculating in a fluid in the flow channel with the nanoneedle and penetration of the cell membrane with the nanoneedle. Aspects of the present application also provide an integration between the flow channel and a cell sorter to form a medical system that selectively and continuously communicates intracellularly with screened cells of interests.

The invention relates to a method for providing a cell line having a desired target protein expression and to a device for selecting cell lines having a desired target protein expression.

In an illustrative embodiment, automated multi-module cell editing instruments are provided to automate multiple edits into nucleic acid sequences inside one or more cells.

In an illustrative embodiment, automated multi-module cell editing instruments are provided to automate multiple edits into nucleic acid sequences inside one or more cells.