STn-Coated CTC Isolation Surfaces for High-Purity Cell Capture
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Solution Overview
Problem
Current methods for isolating circulating tumor cells (CTCs) are inefficient, leading to low recovery rates and contamination with blood cells, particularly due to the lack of a biomarker that is universally expressed across different cancer types and not present in blood cells, resulting in underrepresentation of aggressive CTC populations and inaccurate clinical assessments.
Innovation Solution
Utilizing sialyl-Tn antigen (STn) antibodies to coat CTC isolation devices, which selectively capture CTCs from various cancer types by targeting STn, and employing glycoside hydrolase enzymes like α-neuraminidase for enzymatic detachment, ensuring high purity and viability of captured cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If EpCAM antibodies are used to isolate CTCs, then epithelial cell capture is improved, but metastatic CTC recovery is reduced due to loss of EpCAM expression
Solution Approach 1:
The patent changes the biomarker parameter from EpCAM to STn antigen, which is expressed in both non-metastatic and metastatic CTCs. This parameter change allows consistent capture across different cancer states, resolving the contradiction between reliable epithelial cell capture and metastatic CTC recovery
2Quantity of substance
If current CTC isolation methods are used, then some CTCs are captured, but blood cell contamination occurs reducing purity
Solution Approach 1:
The patent uses STn antigen as an intermediary marker that is specific to CTCs but absent from blood cells. This intermediary enables selective capture of CTCs without co-capture of contaminating blood cells, simultaneously improving quantity and purity
3Reliability
If EpCAM-based isolation is performed, then epithelial cells are enriched, but significant blood cell contamination remains
Solution Approach 1:
The patent extracts the harmful contamination problem by using STn antigen specificity to selectively bind only CTCs while leaving blood cells unbound. This extraction approach removes the contamination issue while maintaining epithelial cell enrichment
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
Enhances the efficiency and specificity of CTC isolation, allowing for accurate assessment of metastasis risk, disease progression, and treatment response by capturing a broader range of CTCs without blood cell contamination, facilitating downstream molecular studies.
Implementation Method 1
contacting the biological sample with a functionalized surface, article or device which is coated with a composition comprising an antibody with affinity for the sialyl-Tn antigen (STn)
Implementation Method 2
detaching the cancer cells bound to the functionalized surface in a viable state using a specific enzymatic treatment
Data Source
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AI summary
The present invention refers to the use of antibodies against sialyl-Tn antigen (STn) or other agents with affinity for STn in a composition for coating Circulating Tumour Cells (CTCs) isolation devices. The present invention further refers to a functionalized surface or article comprising the composition with a STn capturing agent. Another aspect of this invention further refers to a method to produce the article or surface with a coating comprising the said composition and a method to detach the cells bound to this surface employing the use of glycoside hydrolase enzymes such as α- neuraminidase. The composition, surface and methods may be advantageously applied to coating devices to capture CTCs in blood or other body fluids, to improve their efficiency and specificity in isolating CTCs and to improve their accuracy in assessing the risk of metastization, prognostication, monitoring of disease progression, detection of residual disease and evaluation of response to treatment. Thus, the present invention falls within the technical field of medicine, pharmaceutics and biochemistry.