Sample Carrier with Narrow Chamber for Pathogen Detection

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Solution Overview

Problem

Conventional light microscopes struggle to detect small biological objects like viruses due to their size being below the resolution limit and the interference from background fluorescence, making existing advanced microscopy methods like TIRF and confocal microscopy complex, costly, and unsuitable for high-throughput applications.

Innovation Solution

A sample carrier with a narrow sample space and transparent detection window, allowing for reduced background noise by limiting the sample space to only accommodate small objects and using a filter to prevent larger constituents from entering, along with an excitation window for selective excitation and detection of fluorescent markers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If TIRF microscopy is used to reduce background fluorescence, then background noise is reduced, but device complexity and cost increase

Engineering Contradiction:
Improvebackground fluorescenceVSAvoidmicroscopy method complexity
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The invention extracts and eliminates the source of background fluorescence by using a filter element with mesh size smaller than the objects to be detected. This physically removes larger constituents (cells, cell fragments, aggregates) that cause background noise, allowing simple wide-field microscopy to achieve background reduction without complex optical setups

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention employs disposable filter elements that can be integrated into standard sample carriers. These inexpensive filter components enable background reduction in routine microscopy without requiring expensive TIRF microscope systems, making the solution accessible for high-throughput applications

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Object-affected harmful factors

If TIRF microscopy is used to reduce background fluorescence, then background noise is reduced, but ease of operation deteriorates

Engineering Contradiction:
Improvebackground fluorescenceVSAvoidhandling complexity
Core Design Contradiction:
Object-affected harmful factorsVSEase of operation

Solution Approach 1:

The harmful background fluorescence is extracted and removed by physically filtering out larger constituents before detection. This eliminates the need for complex TIRF optical alignment and calibration procedures, allowing operators to use standard microscopy equipment with simple sample preparation

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The filter element performs preliminary separation of objects by size before detection occurs. By removing larger background-producing constituents in advance, the detection step becomes straightforward without requiring sophisticated calibration or specialized operational procedures

Inventive Principle:
Principle #10Preliminary action

3Ease of operation

If conventional light microscope is used for detection, then ease of operation is maintained, but measurement precision deteriorates for small objects

Engineering Contradiction:
Improvehandling simplicityVSAvoiddetection capability for small objects
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The invention converts the limitation of simple wide-field microscopy (which normally suffers from background fluorescence) into an advantage by using a size-based filter. The filter removes larger constituents that cause background noise, allowing the simple microscope to detect small objects with high precision while maintaining ease of operation

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The filter element introduces local size-selective quality to the sample preparation process. By allowing only objects smaller than the mesh size to pass through while blocking larger constituents, the system enables precise detection of small objects using simple microscopy without the complexity of advanced optical methods

Inventive Principle:
Principle #3Local quality

4Ease of operation

If wide field illumination is used for ease of operation, then ease of operation is maintained, but background fluorescence increases

Engineering Contradiction:
Improveillumination simplicityVSAvoidbackground fluorescence
Core Design Contradiction:
Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The source of background fluorescence is extracted and removed by filtering out larger constituents (cells, fragments, aggregates) before illumination and detection. This allows simple wide-field illumination to be used without generating excessive background noise, maintaining both operational simplicity and detection quality

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The filter element performs preliminary size-based separation before the illumination and detection steps. By removing larger background-producing constituents in advance, the subsequent wide-field illumination produces minimal background fluorescence, enabling simple operational procedures to achieve high-quality results

Inventive Principle:
Principle #10Preliminary action

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 the detection of small biological objects with reduced background noise and fluorescence, facilitating high-throughput detection without the need for complex calibration and handling, making it suitable for routine use and mass diagnosis.

Implementation Method 1

the wall has at least one region which is transparent to a detection radiation originating from the sample and which acts as detection window

Methodology Applied
Scientific EffectTransparency to detection radiation:

Implementation Method 2

One such solution from Xfold imaging is optimized to only one wavelength or a few wavelengths

Methodology Applied
Scientific EffectPhysical filtration: Filter (physical)

Implementation Method 3

Biological objects, in particular, can be provided with specific markings, for example proteins or probes (henceforth also: markers), which emit a detection radiation

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 4

TIRF (total internal reflection fluorescence) microscopy can be used as detection method. As a result of an evanescent field arising in a small space, it is only marked objects in the vicinity of for example a surface of a transilluminated sample carrier that are excited

Methodology Applied
Scientific EffectTotal internal reflection: Total Internal Reflection

Data Source

PatentUS20240342707A1Sample carrier, use thereof, and methods, in particular for detecting pathogens
Publication Date: 2024.10.17 CARL ZEISS MICROSCOPY GMBH
  • US20240342707A1 patent drawing
  • US20240342707A1 patent drawing
  • US20240342707A1 patent drawing

AI summary

The disclosure relates to a sample carrier, the use thereof, and methods, in particular for detecting pathogens. The sample carrier has a sample chamber for receiving a sample, which chamber is enclosed by a wall, and an access opening for filling the sample chamber with the sample; the wall has at least one region which is transparent to detection radiation coming from the sample and acts as a detection window. According to the invention, the sample chamber has, in a direction perpendicular to the transparent region of the wall, a clear distance between the opposing inner faces of the wall of at most 50 μm, in particular, at most 25 μm.