Translating Cap Meniscus Fluid Delivery for Biological Staining

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Solution Overview

Problem

Current automated staining methods for biological samples are limited by the slow diffusion of large biomolecules into tissue sections, requiring high concentrations and long incubation times, which leads to wasteful usage of expensive reagents and non-specific background staining due to large reagent volumes and inefficient mixing.

Innovation Solution

A method and apparatus using a translating cap with a curved surface to form a moving liquid meniscus layer between the cap and the biological sample, allowing for faster and more efficient delivery of conjugate biomolecules, with the cap moving back and forth over the sample to enhance mixing and rinsing through capillary action and serial dilution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If large volumes of reagent are used in direct contact with tissue sections, then conjugate biomolecules can diffuse into tissue, but this results in wasteful usage of expensive reagents and non-specific background staining

Engineering Contradiction:
Improvereagent volumeVSAvoidconjugate waste
Core Design Contradiction:
Quantity of substanceVSLoss of substance

Solution Approach 1:

The patent uses a hydrodynamic approach where a stream of reagent flows tangentially across the tissue section surface, creating a thin liquid layer through fluid dynamics rather than using large static pools. The reagent stream is directed at an angle to create shear flow that enhances mixing and conjugate delivery while minimizing reagent volume.

Inventive Principle:
Principle #29Pneumatics and hydraulics

Solution Approach 2:

The patent transforms the static incubation process into a dynamic flow system. The reagent continuously flows across the tissue surface rather than remaining stationary, creating dynamic mixing conditions that enhance conjugate penetration while reducing the total reagent volume needed compared to static puddle methods.

Inventive Principle:
Principle #15Dynamics

2Productivity

If high concentrations of conjugate are used to increase diffusion rate, then processing time is reduced, but this causes excessive conjugate to be entrapped in tissue and causes high levels of non-specific background staining

Engineering Contradiction:
Improveprocessing speedVSAvoidstaining specificity
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The tangential flow creates a hydrodynamic environment where the reagent stream continuously moves across the tissue surface. This flow pattern enhances the delivery of conjugate to the tissue while the continuous movement prevents excessive conjugate accumulation and entrapment, maintaining staining specificity even at higher concentrations.

Inventive Principle:
Principle #29Pneumatics and hydraulics

Solution Approach 2:

The system uses periodic or continuous flow of reagent across the tissue surface, creating repeated cycles of conjugate delivery and removal. This periodic action allows sufficient conjugate to penetrate the tissue for rapid staining while excess conjugate is continuously washed away, preventing non-specific background staining.

Inventive Principle:
Principle #19Periodic action

3Area of stationary object

If large pools of reagent are used for incubation, then tissue can be adequately covered, but this requires large volumes of rinse liquid to physically displace the reagent which produces large volumes of hazardous waste

Engineering Contradiction:
Improvetissue coverageVSAvoidwaste liquid volume
Core Design Contradiction:
Area of stationary objectVSLoss of substance

Solution Approach 1:

The patent replaces large static reagent pools with a focused tangential flow stream that covers the tissue surface efficiently. This hydrodynamic approach reduces the reagent volume from hundreds of microliters to just a few microliters while maintaining adequate tissue coverage through the shearing action of the flow.

Inventive Principle:
Principle #29Pneumatics and hydraulics

Solution Approach 2:

The patent extracts only the essential function of reagent coverage from the traditional large-pool approach. By using a targeted tangential flow, the system delivers reagent coverage where needed on the tissue surface without requiring large volumes, thereby eliminating the need for large rinse volumes and reducing hazardous waste.

Inventive Principle:
Principle #2Taking out (Extraction)

4Stability of the object's composition

If present instruments mix reagent by alternating tangential air jets onto an overlaying oil layer, then evaporation is minimized, but this mixing is slow and not particularly vigorous

Engineering Contradiction:
Improveevaporation controlVSAvoidmixing efficiency
Core Design Contradiction:
Stability of the object's compositionVSProductivity

Solution Approach 1:

The patent uses direct liquid flow hydrodynamics instead of gas-liquid-oil multi-phase systems. The tangential stream of reagent creates vigorous mixing through shear forces and flow patterns, eliminating the need for air jets and oil layers. This approach provides both effective mixing and evaporation control through the continuous liquid flow.

Inventive Principle:
Principle #29Pneumatics and hydraulics

Solution Approach 2:

The patent creates dynamic mixing conditions through the moving tangential reagent stream, which continuously flows across the tissue surface. This dynamic approach produces vigorous mixing that is much more effective than the slow mixing achieved by alternating air jets, while the continuous flow naturally controls evaporation.

Inventive Principle:
Principle #15Dynamics

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

This approach enables quicker processing of biological samples with reduced reagent usage, minimizing non-specific staining and waste, while maintaining effective conjugate delivery and tissue handling.

Implementation Method 1

moving a curved surface wetted with a solution in proximity to said biological sample whereby the distance separating said wetted curved surface and said biological sample is sufficient to form a moving liquid meniscus layer between the two

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Data Source

PatentUS7820381B2Method and apparatus for applying fluids to a biological sample
Publication Date: 2010.10.26 VENTANA MEDICAL SYSTEMS INC
  • US7820381B2 patent drawing
  • US7820381B2 patent drawing
  • US7820381B2 patent drawing

AI summary

The invention is directed to a method of contacting a biological sample with a solution, comprising the steps of moving a curved surface wetted with the solution in proximity to the biological sample whereby the distance separating the wetted curved surface and the biological sample is sufficient to form a moving liquid meniscus layer between the two. The invention is also directed to an apparatus for contacting a biological sample suspected of containing a biomarker with a solution, comprising a platform for supporting a microscope slide having a biological sample thereon; a translating cap having a curved lower surface positioned above the platform, the curved lower surface being in proximity to a biological sample when in operation; means for moving the translating cap back and forth over the biological sample; and means for applying and removing liquid to and from the cap.