Fluorescence-Labeled Probe Cells for Antibody Detection

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Solution Overview

Problem

Current blood group antigen antibody detection systems are inadequate for accurately identifying specific antibodies, particularly in cases of pan-agglutination, auto-reactive antibodies, or antibodies against rare antigens, leading to false interpretations and potential missed serious antibodies, and lack robust, rapid, and affordable tests for platelets and granulocytes.

Innovation Solution

A method using fluorescence-labeled cells specific for each antigen, where a sample is contacted with probing cells expressing detectable labels and an antibody binding agent, allowing for the detection of antibody presence through signal detection, and a method for removing antibodies by trapping them with antigen-expressing cells, enabling precise identification and depletion of antibodies in serum samples.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional cell panels are used for antibody detection, then the method is simple and widely applicable, but accuracy deteriorates in cases of pan-agglutination, auto-reactive antibodies, or antibodies against rare antigens

Engineering Contradiction:
Improveantibody detection accuracyVSAvoidapplicability to all antibody types
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent segments the antibody detection process by creating separate probe cells for different antigen types (RBC antigens, platelet antigens, granulocyte antigens). Each probe cell is specifically engineered to express only one or a limited set of antigens, allowing targeted detection of specific antibody species without interference from pan-agglutination or auto-reactive antibodies. This segmentation enables accurate identification of antibodies against rare antigens that would be missed in conventional mixed panels.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent applies local quality by赋予ing each probe cell specific characteristics - different probe cells express different antigen combinations tailored to detect specific antibody specificities. The probe cells are locally optimized with fluorescent labeling and specific antigen expression patterns to enhance detection sensitivity for particular antibody types while maintaining overall system versatility.

Inventive Principle:
Principle #3Local quality

2Productivity

If standard diagnostic tests are used, then routine cases are handled effectively, but specific situations like pan-agglutination or rare antigen antibodies lead to false interpretations

Engineering Contradiction:
Improvethroughput for routine casesVSAvoiddiagnostic reliability in complex cases
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent performs preliminary action by pre-engineering probe cells with specific antigen expressions and fluorescent labels before the detection process. The probe cells are prepared in advance with known antigen profiles, allowing the system to automatically differentiate between various antibody specificities based on predetermined reaction patterns. This preliminary preparation ensures that even complex cases like pan-agglutination can be reliably interpreted through systematic analysis of probe cell reactions.

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If fluorescence-labeled probe cells are used, then detection accuracy improves, but system complexity increases

Engineering Contradiction:
Improveantibody species identification accuracyVSAvoidsystem structure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent employs color changes through fluorescent labeling of probe cells to achieve precise antibody identification. Different probe cells are labeled with distinct fluorescent markers that emit different colors or wavelengths, enabling multiplex detection of multiple antibody specificities simultaneously. This optical differentiation allows the system to accurately identify antibody species while managing complexity through standardized fluorescent labeling protocols and automated optical detection systems.

Inventive Principle:
Principle #32Color changes

4Ease of manufacture

If conventional methods are used for platelet and granulocyte antibody detection, then the process is simplified, but robustness and standardization deteriorate

Engineering Contradiction:
Improvetest preparation simplicityVSAvoidtest robustness and standardization
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent applies copying by creating standardized probe cell lines that replicate specific antigen expressions for platelet and granulocyte antigens. These engineered probe cells serve as consistent, reproducible copies of the target antigens, enabling standardized detection protocols across different laboratories and time points. The probe cells are manufactured with defined genetic constructs that ensure consistent antigen expression levels and patterns, thereby achieving both ease of manufacture through cell line propagation and high reliability through standardized antigen presentations.

Inventive Principle:
Principle #26Copying

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 simplifies the detection of blood group antigens on RBCs, platelets, and granulocytes, improving accuracy and reducing false positives, and allows for the removal of specific antibodies from serum samples, enhancing diagnostic capabilities and transfusion safety.

Implementation Method 1

The system uses fluorescence labeled cells specific for each antigen and hence, for each antibody species

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

an antibody binding agent, wherein the antibody binding agent is coupled to a first detectable label and is capable of binding antibodies

Methodology Applied
Scientific EffectAntibody-antigen binding:

Implementation Method 3

a method for removing antibodies from a sample such as a serum sample

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentUS10670587B2Antibody detection method and system
Publication Date: 2020.06.02 DRK BLUTSPENDEDIENST BADEN WURTTEMBERG HESSEN GGMBH
  • US10670587B2 patent drawing
  • US10670587B2 patent drawing
  • US10670587B2 patent drawing

AI summary

The present invention provides a cellular system for the detection of the presence of one or more antibody species in sample, preferably a serum or plasma sample. The method is in particular useful for the analysis of patients who have been sensitized against blood group antigens expressed on erythrocytes, platelets or granulocytes. The system uses fluorescence labeled cells specific for each antigen and hence, for each antibody species. Provided are the methods, system and diagnostic kits for performing the methods of the invention. In addition, the present invention discloses a method for removing antibodies from a sample such as a serum sample. Such a method is useful for absorbing antibodies from poly-agglutinating sera.