Ligand-Imaging Conjugate Flow Cytometry for Pathogenic Cell Detection
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Solution Overview
Problem
Current methods for detecting and quantifying pathogenic cells in ex vivo patient body fluids lack sensitivity and biocompatibility, making it difficult to accurately diagnose and monitor diseases such as cancer at early stages.
Innovation Solution
The use of ligand-imaging agent conjugates that bind to pathogenic cells, combined with flow cytometry techniques, allows for the detection and quantification of these cells in ex vivo samples, enhancing sensitivity and specificity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional ex vivo detection methods are used, then the sample volume required is large, but the sensitivity of detection is low
Solution Approach 1:
The patent changes the chemical structure parameters of the detection probe by incorporating PEG linkers of specific lengths (e.g., 2-atom, 7-atom, 16-atom, 24-atom spacers) between the ligand and imaging agent. This parameter optimization enhances the probe's ability to bind to pathogenic cells while maintaining biocompatibility, thereby improving detection sensitivity with smaller sample volumes
Solution Approach 2:
The patent creates composite detection probes by conjugating ligands (such as folate or PSMA inhibitors) with imaging agents through PEG linkers. This composite structure combines the target-specific binding capability of the ligand with the detection capability of the imaging agent, achieving high sensitivity detection in small sample volumes
2Reliability
If conventional ex vivo techniques are used, then the detection can be performed, but the biocompatibility is insufficient
Solution Approach 1:
The patent introduces PEG linkers as intermediary structures between the ligand and imaging agent. These PEG spacers improve biocompatibility by reducing non-specific binding and enhancing the probe's solubility and stability in physiological environments, while maintaining detection accuracy through optimized linker lengths
Solution Approach 2:
The patent optimizes the physical-chemical parameters of the detection probe by varying the PEG linker length and composition. This parameter tuning enhances biocompatibility by reducing immunogenicity and improving cellular uptake, while preserving detection precision through maintained ligand-receptor binding affinity
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 the early detection and quantification of pathogenic cells, improving cancer prognosis and monitoring, and can be applied to various body fluids, providing a more accurate and sensitive method for disease diagnosis.
Implementation Method 1
combining with an ex vivo patient sample a composition comprising a conjugate or complex of the general formula Ab-X, wherein the group Ab comprises a ligand that binds to the pathogenic cells
Implementation Method 2
detecting the pathogenic cells that express a receptor for the ligand using flow cytometry
Data Source
AI summary
The invention relates to a method for diagnosing a disease state mediated by pathogenic cells. The method comprises the steps of combining with an ex vivo patient sample a composition comprising a conjugate or complex of the general formulaAb-Xwherein the group Ab comprises a ligand that binds to the pathogenic cells and the group X comprises an imaging agent, and detecting the pathogenic cells that express a receptor for the ligand using flow cytometry.