Microscope Stage Automation for Multi-Sample Fluid Handling

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Solution Overview

Problem

Manually pipetting samples in high-throughput experiments is time-consuming and prone to contamination, requiring multiple reagents to be added quickly while reactions may take minutes to days, necessitating automation to improve efficiency and reduce human error.

Innovation Solution

A microscope stage with a receiving surface and liquid handling head that allows automated dispensing and aspiration of fluids onto sample carriers, featuring a surface and head moving device for alignment with any sample area, and a replaceable fluidic link for rapid line changes, enabling flexible and efficient fluid handling.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Extent of automation

If manual pipetting is used for high-throughput experiments, then flexibility in handling samples is maintained, but time consumption increases and contamination risk increases

Engineering Contradiction:
Improveautomation of pipettingVSAvoidcomplexity of fluid handling system
Core Design Contradiction:
Extent of automationVSDevice complexity

Solution Approach 1:

The fluid handling system is segmented into modular components: a liquid handling head with multiple nozzles, a sample carrier with multiple sample areas, and a stage with independent movement capabilities. This segmentation allows each component to perform its function independently while maintaining overall system flexibility and reducing complexity through standardized interfaces.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The liquid handling head is designed with multiple nozzles that can dispense different reagents to multiple sample areas simultaneously. The stage can move in multiple directions to position any sample area under the imaging area. This multi-functionality allows a single device to handle various experiment configurations without requiring multiple specialized tools.

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

2Productivity

If multiple reagents are added quickly to samples, then experiment throughput is improved, but risk of contamination increases

Engineering Contradiction:
Improvethroughput of sample processingVSAvoidcontamination risk
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The system performs automated fluid handling without human intervention. The liquid handling head automatically dispenses reagents, the stage automatically positions samples, and the entire process can be controlled via software. This self-service capability eliminates human contact with samples during critical operations, preventing contamination while maintaining high throughput.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The automated liquid handling head acts as an intermediary between the reagent reservoirs and the samples. Instead of direct human contact, the system uses programmable robotic dispensing to transfer reagents, creating a barrier that prevents contamination while enabling rapid multi-reagent addition.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If human interaction is required for pipetting, then ease of operation is maintained, but experiment efficiency decreases

Engineering Contradiction:
Improveexperiment efficiencyVSAvoidease of automated operation
Core Design Contradiction:
ProductivityVSEase of operation

Solution Approach 1:

The patent replaces manual mechanical pipetting operations with an automated robotic system. The liquid handling head with programmable movement replaces the manual pipette, and the motorized stage replaces manual sample positioning. This substitution increases productivity by eliminating repetitive manual tasks while maintaining ease of operation through software control.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The system incorporates dynamic movement capabilities with the stage able to reposition between imaging and liquid handling areas, and the liquid handling head able to move between different sample areas. This dynamic design allows the system to adapt to different experiment protocols while being controlled through standardized interfaces, maintaining ease of operation.

Inventive Principle:
Principle #15Dynamics

4Adaptability or versatility

If the receiving surface position is fixed relative to the liquid handling head, then device complexity is reduced, but flexibility in dispensing fluids to different sample areas is limited

Engineering Contradiction:
Improveflexibility in fluid dispensingVSAvoidcomplexity of movement coordination
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent merges the movement functions of the stage and liquid handling head into a coordinated system. Both components can move independently but are controlled through a unified software interface that synchronizes their positions. This merging allows flexible dispensing to any sample area while managing complexity through integrated control.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The system adds dimensional flexibility by allowing movement in multiple directions: the stage moves samples in X-Y directions to different positions, and the liquid handling head moves in Z-direction for dispensing. This multi-dimensional movement capability provides versatility in fluid dispensing while the independent control of each axis manages the complexity.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Data Source

PatentEP4617639A1Microscope stage, replaceable fluidic link and method for examining a sample
Publication Date: 2025.09.17 LEICA MICROSYSTEMS CMS GMBH
  • EP4617639A1 patent drawingFigure 1
  • EP4617639A1 patent drawingFigure 2
  • EP4617639A1 patent drawingFigure 3

AI summary

In a first aspect, a microscope stage (100, 500, 600) is provided comprising a receiving surface (102) configured to receive at least a first sample carrier (104, 200) with a plurality of sample areas (202, 204), an imaging area (206), and a surface moving device (118) configured to move the receiving surface (102) along at least two directions, wherein the surface moving device (118) has a range of movement along the at least two directions such that any one of the sample areas of the plurality of sample areas (202, 204) is alignable with the imaging area (206). The microscope stage further comprises at least one liquid handling head (106, 502, 602) configured to dispense fluids onto the sample carrier (104, 200), and a head moving device (108, 110, 112) configured to move the at least one liquid handling head (106, 502, 602) along at least two directions, wherein the head moving device (108, 110, 112) has a range of movement along the at least two directions such that the at least one liquid handling head (106, 502, 602) is alignable with any one of the sample areas (202, 204) of the plurality of sample areas (202, 204). In further aspects a corresponding microscope and method are provided.