Automated Multi-Module Cell Editing Instruments

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Solution Overview

Problem

Current genome editing methods with engineered nucleases are not compatible with automation due to low efficiencies and challenges with cell transformation, growth measurement, and cell selection, limiting the complexity and nature of cell populations that can be created.

Innovation Solution

Automated multi-module cell editing instruments and systems that integrate nucleic acid introduction, editing, and cell growth, allowing for recursive genome editing and the generation of libraries of living cells with desired genomic changes using nuclease-directed genome editing techniques.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Extent of automation

If traditional genome editing methods with engineered nucleases are used, then cell editing can be performed, but automation compatibility is poor due to low efficiencies and challenges with cell transformation, growth measurement, and cell selection

Engineering Contradiction:
Improveautomation compatibilityVSAvoidediting efficiency
Core Design Contradiction:
Extent of automationVSReliability

Solution Approach 1:

The genome editing process is divided into separate modular stages including cell preparation, nucleic acid introduction, editing, growth measurement, and cell selection. Each stage can be independently optimized and automated, resolving the contradiction between automation compatibility and editing efficiency by allowing specialized automation for each step rather than requiring complete automation of a single integrated process

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces intermediate steps and components such as selectable markers, reporter genes, and standardized cell culture protocols that mediate between the editing process and automation systems. These intermediaries enable automated detection and selection while maintaining high editing efficiency through standardized, measurable outcomes

Inventive Principle:
Principle #24Intermediary (Mediator)

2Adaptability or versatility

If complex cell populations are generated through multiple rounds of editing, then genomic diversity increases, but the process becomes more cumbersome and less scalable

Engineering Contradiction:
Improvegenomic diversityVSAvoidprocess complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent establishes universal protocols and standardized components that can be applied across multiple editing rounds and different cell types. This includes standardized nucleic acid introduction methods, universal selectable markers, and common growth measurement protocols that reduce process complexity while enabling generation of diverse cell populations through recursive editing

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

Multiple genome editing operations are nested within a standardized automated workflow framework. Each editing round follows the same structured protocol, with inner editing steps contained within the outer framework of cell preparation, transformation, selection, and analysis, allowing complex multi-round editing to be managed through repetitive application of a simple core protocol

Inventive Principle:
Principle #7Nested doll (Nesting)

3Productivity

If manual cell processing methods are used, then flexibility in protocol adjustment is maintained, but productivity and scalability are limited

Engineering Contradiction:
ImprovescalabilityVSAvoidprotocol flexibility
Core Design Contradiction:
ProductivityVSEase of operation

Solution Approach 1:

The patent employs standardized parameters and controlled variables in cell culture and editing protocols that can be systematically adjusted through defined parameter changes rather than arbitrary protocol modifications. This allows automated systems to maintain productivity while enabling flexibility through systematic parameter optimization rather than manual protocol rewriting

Inventive Principle:
Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Enables efficient and automated introduction of nucleic acids into cells, facilitating the creation of diverse cell libraries with specific genomic edits, improving editing efficiency and scalability in generating complex cell populations.

Implementation Method 1

a flow-through electroporation device to introduce the assembled nucleic acids into the electrocompetent cells

Methodology Applied
Scientific EffectElectroporation: Electrical Impedance Tomography

Data Source

PatentUS11597921B2Automated cell processing methods, modules, instruments, and systems
Publication Date: 2023.03.07 INSCRIPTA INC
  • US11597921B2 patent drawing
  • US11597921B2 patent drawing
  • US11597921B2 patent drawing

AI summary

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.