Automated Single Cell Processing System for High-Throughput Analysis

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Solution Overview

Problem

Current single cell processing and analysis systems are time-consuming, prone to user errors, and require expert intervention, limiting their accessibility and throughput due to the lack of automation and high costs associated with high-throughput single-cell gene expression profiling and biomarker analysis.

Innovation Solution

An automated system for single cell sample processing that includes a deck supporting sample processing elements, a gantry for actuating tools, and a base with control subsystems, enabling integrated and real-time imaging, fluid handling, and temperature control, which automates steps like cell capture, lysis, reverse transcription, and library preparation, reducing user intervention and increasing efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If manual single cell processing is performed, then flexibility and adaptability are maintained, but processing time increases and throughput decreases

Engineering Contradiction:
ImprovethroughputVSAvoidautomation level
Core Design Contradiction:
ProductivityVSExtent of automation

Solution Approach 1:

The system performs self-service through automated pipetting, heating, cooling, and sample processing steps without requiring manual intervention. The automated liquid handling system delivers reagents and performs processing steps autonomously, enabling high-throughput single-cell analysis while maintaining protocol consistency and reducing user skill requirements.

Inventive Principle:
Principle #25Self-service

2Productivity

If automated single cell processing is implemented, then throughput increases, but system complexity increases

Engineering Contradiction:
ImprovethroughputVSAvoidsystem complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The system is divided into modular functional components including an automated liquid handling system, temperature control subsystems, imaging systems, and data processing modules. Each module performs a specific function and can operate independently, making the overall complex system manageable and easier to maintain while achieving high-throughput processing.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The automated liquid handling system serves multiple functions including reagent dispensing, sample transfer, and protocol execution. The temperature control system manages both heating and cooling operations. This multi-functionality reduces the need for separate dedicated devices, thereby managing system complexity while maintaining high throughput capability.

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

3Ease of operation

If expert user intervention is required, then processing accuracy is maintained, but accessibility and ease of operation decrease

Engineering Contradiction:
Improveuser accessibilityVSAvoidprocessing accuracy
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The system incorporates feedback mechanisms where the control system monitors and adjusts processing parameters in real-time. The automated liquid handling system tracks reagent volumes and flow rates, while temperature control systems continuously regulate conditions. This feedback ensures consistent processing accuracy without requiring expert user intervention, thereby improving both accessibility and reliability.

Inventive Principle:
Principle #23Feedback

4Adaptability or versatility

If high-cost cutting edge instrument systems are used, then analysis capability is improved, but cost-effectiveness decreases and access is limited

Engineering Contradiction:
Improveanalysis capabilityVSAvoidcost-effectiveness
Core Design Contradiction:
Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The system merges multiple high-cost individual instruments into a single integrated platform that performs cell capture, lysis, reverse transcription, library preparation, and imaging in one unified system. This consolidation reduces overall system cost while maintaining cutting-edge analysis capability, making advanced cytometry tools more accessible and cost-effective.

Inventive Principle:
Principle #5Merging (Combining)

Data Source

PatentUS20230338952A1System and method for automated single cell processing and analyses
Publication Date: 2023.10.26 BIO RAD LABORATORIES INC
  • US20230338952A1 patent drawing
  • US20230338952A1 patent drawing
  • US20230338952A1 patent drawing

AI summary

A system and method for automated single cell capture and processing is described, where the system includes a deck supporting and positioning a set of sample processing elements (including an integrated imaging subsystem); a gantry for actuating tools for interactions with the set of sample processing elements supported by the deck; and a base supporting various processing subsystems and a control subsystems in communication with the processing subsystems. The system can automatically execute workflows associated with single cell processing, including antibody detection, other protein detection, mRNA detection, and/or other applications associated with spatial transcriptomics.