Functionalized Mesh for High-Throughput CTC Capture
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Solution Overview
Problem
Current methods for capturing circulating tumor cells (CTCs) from blood samples face challenges such as low throughput, poor efficiency, high false positive rates, and difficulties in industrialization, with existing technologies either being costly, consuming excessive blood, or unable to capture living cells for RNA sequencing and medication guidance.
Innovation Solution
A method utilizing a functionalized mesh apparatus with antibodies specifically binding to epithelial cell adhesion molecules, allowing for high-throughput capture and sorting of CTCs, involving steps of medium flow, debris removal, cell detachment, and collection, with the mesh substrate coated with gold or noble metals and antibodies attached using Traut's reagent or biotin-avidin linkage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional magnetic activated cell sorting method is used, then sensitivity and specificity are improved, but operation speed and throughput deteriorate
Solution Approach 1:
The invention divides the capture surface into multiple functionalized posts arranged in arrays, where each post can independently capture cells. This segmentation allows parallel processing of multiple cells simultaneously, thereby increasing throughput while maintaining the high specificity of magnetic-activated cell sorting through targeted antibody-functionalized posts.
Solution Approach 2:
The invention introduces functionalized posts with magnetic beads as intermediaries between the magnetic field and target cells. The magnetic beads attached to antibody-functionalized posts serve as mediators that enable specific cell capture through magnetic activation, combining the specificity of antibody binding with the speed of magnetic manipulation for high-throughput sorting.
2Ease of operation
If membrane microfiltration or density gradient centrifugation is used, then ease of operation is improved, but specificity deteriorates with high false positive rate
Solution Approach 1:
The invention applies local quality by functionalizing specific regions (posts) with targeted antibodies that recognize specific cell surface markers. This localized functionalization ensures that only cells expressing the target antigen are captured with high specificity, while maintaining the simple operational workflow of passing samples through the device without complex preparation steps.
3Ease of operation
If microfluidic devices with functionalized posts are used, then ease of operation is improved, but cost and false negative rate increase
Solution Approach 1:
The invention uses replicated arrays of functionalized posts that can be manufactured through scalable techniques. By copying the functionalized post structure across multiple locations in the device, the system achieves high throughput capability while maintaining consistent capture performance, reducing false negatives through redundant capture opportunities, and lowering per-unit cost through规模化 production.
4Measurement precision
If Cell Search device is used, then sensitivity and specificity are improved, but blood consumption and cost increase
Solution Approach 1:
The invention transitions from a two-dimensional surface capture approach to a three-dimensional array of functionalized posts extending into the flow path. This dimensional change increases the effective capture surface area within a compact volume, allowing high-sensitivity detection with smaller blood sample volumes by providing multiple capture opportunities as cells pass through the three-dimensional post array.
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
The method achieves high specificity and efficiency in capturing CTCs, reducing clogging risks, enabling live cell collection, and facilitating RNA sequencing, while being more cost-effective and scalable compared to existing microfluidic devices.
Implementation Method 1
said functional layer comprises capturing substances that can specifically bind with said target cells or molecules
Implementation Method 2
said mesh substrate comprises: a stainless steel body; and a surface coating provided on the surface of said stainless steel body, wherein said surface coating is made of gold or other noble metal
Data Source
AI summary
Disclosed is a method for capturing target cells or molecules in solution, comprising steps of: (I) getting medium containing said target cells or molecules into an apparatus comprising a capturing device for capturing said target cells or molecules; (II) getting said medium flow through said capturing device; (III) removing unbound debris, cells and molecules; (IV) getting said target cells or molecules detached from the capturing device; and (V) collecting said target cells or molecules; wherein said capturing device comprises at least one functionalized mesh comprising a mesh substrate and a functional layer formed on said mesh substrate, wherein said functional layer comprises capturing substances that can specifically bind with said target cells or molecules. The method has high specificity, as well as high throughput, and is suitable for capturing cells or molecules in a solution or expressed at the surface of cell membranes. It is particularly suited to capture and sort circulating tumor cells.