Gravity-Driven Perfusion System for Drift-Free Microscopy

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Solution Overview

Problem

Conventional perfusion systems for microscopy suffer from sample drift, mechanical vibrations, hydrodynamic fluctuations, and heat dissipation issues, making them unsuitable for high-resolution and long-term imaging, especially for 3D localization microscopy.

Innovation Solution

A perfusion system utilizing a sample chamber with inlet and outlet openings, a reservoir positioned above the inlet, and a wick forming a fluid-tight connection with the outlet, creating a capillary-driven laminar flow that maintains a stable spatial pressure gradient and minimizes sample drift, suitable for 3D localization microscopy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If electrically-driven pumps are used to perfuse media through the sample chamber, then the perfusion flow can be controlled and maintained, but mechanical vibrations are generated that interfere with image capture events in optical high-resolution or super-resolution microscopy

Engineering Contradiction:
Improveperfusion flow controlVSAvoidmechanical vibrations
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces electrically-driven pumps with a gravity-driven perfusion system. The reservoir is positioned above the sample chamber, allowing media to flow through the chamber via gravity alone, eliminating mechanical vibrations while maintaining controlled perfusion flow.

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

Solution Approach 2:

The patent utilizes hydrostatic pressure principles by positioning the reservoir at a specific height above the sample chamber. This creates a controlled pressure gradient that drives media flow through the chamber without requiring mechanical pumping, thus avoiding vibrations.

Inventive Principle:
Principle #29Pneumatics and hydraulics

2Productivity

If electrically-driven pumps are used to perfuse media through the sample chamber, then media can be delivered to the sample, but hydrodynamic fluctuations and flow variations occur within the sample chamber that negatively affect imaging accuracy

Engineering Contradiction:
Improvemedia deliveryVSAvoidimaging accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent replaces dynamically controlled electric pumps with a static gravity-driven system. This eliminates pump cycles and hydrodynamic fluctuations, providing stable, steady flow conditions that improve imaging accuracy while maintaining effective media delivery.

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

3Productivity

If electrically-driven pumps are used to perfuse media through the sample chamber, then media flow can be regulated, but pressure is created within the sample chamber that causes deformation or loss of cellular adherence and sample drift

Engineering Contradiction:
Improvemedia flow regulationVSAvoidsample stability
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The patent replaces pressure-generating electric pumps with a gravity-driven system that delivers media through gentle gravitational force. This maintains soft pressure conditions that preserve cellular adherence and prevent sample drift while regulating media flow effectively.

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

4Productivity

If electrically-driven pumps are used to perfuse media through the sample chamber, then media can be circulated, but heat is dissipated into the perfusion media and sample chamber, affecting thermal characteristics and biochemical reactivity

Engineering Contradiction:
Improvemedia circulationVSAvoidthermal characteristics
Core Design Contradiction:
ProductivityVSTemperature

Solution Approach 1:

The patent replaces heat-generating electric pumps with a passive gravity-driven circulation system. This eliminates electrical heating and mechanical friction, maintaining stable thermal characteristics in the sample chamber while preserving effective media circulation.

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

5Productivity

If syringe and pipette are used to inject media through the sample chamber inlet, then media can be delivered to the sample, but mechanical position changes create pressure differentials that cause drift and deformation of the sample chamber

Engineering Contradiction:
Improvemedia injectionVSAvoidchamber stability
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The patent replaces mechanically actuated syringes and pipettes with a gravity-driven reservoir system. This eliminates mechanical position changes and associated pressure differentials, maintaining chamber stability while delivering media effectively through the inlet.

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

6Productivity

If syringe and pipette systems are used for perfusion, then media can be injected into the sample chamber, but an open chamber inlet port makes it difficult to control exposure of the sample chamber to ambient gases

Engineering Contradiction:
Improvemedia injection capabilityVSAvoidambient gas exposure
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces open syringe/pipette injection systems with a closed gravity-driven reservoir system. The reservoir and tubing form a closed loop that minimizes exposure to ambient gases while maintaining the ability to deliver media to the sample chamber through the inlet.

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

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

The system achieves drift-free imaging conditions over long acquisition times, ensuring accurate and high-resolution images by eliminating vibrations and heat dissipation, and allowing for even distribution of perfusion media, suitable for 3D localization microscopy.

Implementation Method 1

A capillary tension of the wick contributes to a laminar flow of fluid across an optical detection area of the sample chamber

Methodology Applied
Scientific EffectCapillary tension: Capillary Pressure

Implementation Method 2

a reservoir, which is in fluid communication with the inlet opening and positioned above the inlet opening in a direction opposite the force of gravity

Methodology Applied
Scientific EffectGravity: Gravitation

Data Source

PatentUS20230408838A1Perfusion systems for drift-free microscopy
Publication Date: 2023.12.21 FEI DEUT
  • US20230408838A1 patent drawing
  • US20230408838A1 patent drawing
  • US20230408838A1 patent drawing

AI summary

A perfusion system for reducing or eliminating sample drift during microscopy imaging includes a sample chamber that has an inlet opening associated therewith. The perfusion system also includes a reservoir, which is in fluid communication with the inlet opening and positioned above the inlet opening in a direction opposite the force of gravity. The perfusion system includes an outlet opening associated with the sample chamber. Furthermore, the perfusion system includes a wick. A first portion of the wick forms a fluid-tight connection with the outlet opening. A second portion of the wick is disposed within a waste tank. A capillary tension of the wick contributes to a laminar flow of fluid across an optical detection area of the sample chamber.