Personalized Microfiltration for CTC Isolation

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Solution Overview

Problem

Current microfiltration systems for detecting circulating tumor cells (CTCs) lack personalized approaches and fail to achieve high efficiency and purity due to fixed parameters, ignoring individual differences in blood viscosity and mechanical properties between cancer patients and healthy individuals.

Innovation Solution

A method involving pretreatment of blood samples to remove red blood cells, measuring hemorheological parameters, determining filtration parameters based on these measurements, and subjecting the samples to microfiltration using optimized capillary number (Ca) and normalized cell diameter (d*) for efficient CTC isolation, along with optional steps for cell identification and protein/miRNA detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If fixed filtration parameters are used in microfiltration systems, then the system structure is simple and easy to operate, but the capture efficiency and purity of CTCs are insufficient due to ignoring individual differences in blood viscosity

Engineering Contradiction:
Improvecapture efficiency of CTCsVSAvoidcomplexity of microfiltration system
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent measures hemorheological parameters (blood viscosity, cell deformability) before microfiltration to determine personalized filtration parameters. This preliminary characterization enables optimized CTC capture by adjusting the capillary number based on individual patient properties, resolving the contradiction between simple fixed-parameter systems and efficient personalized separation.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent dynamically adjusts filtration parameters (flow rate, pressure, capillary number) based on measured hemorheological properties of each patient's blood sample. By changing parameters according to individual blood viscosity and cell mechanical properties, the system achieves high capture efficiency without requiring complex adaptive hardware, thus resolving the contradiction between simplicity and effectiveness.

Inventive Principle:
Principle #35Parameter changes

2Manufacturing precision

If fixed filtration parameters are applied to all patients, then the operation process is standardized and simple, but the purity of isolated CTCs is reduced due to variations in blood properties among individuals

Engineering Contradiction:
Improvepurity of CTC isolationVSAvoidsimplicity of filtration procedure
Core Design Contradiction:
Manufacturing precisionVSEase of operation

Solution Approach 1:

The system performs preliminary measurement of hemorheological parameters for each patient before filtration. This advance characterization allows determination of personalized filtration conditions that account for individual blood viscosity and cell deformability differences, achieving high purity CTC isolation while maintaining procedural simplicity through automated parameter selection.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent implements a feedback mechanism where measured hemorheological parameters from each patient's blood sample inform the selection of optimal filtration parameters. This closed-loop approach ensures high purity CTC isolation by adapting to individual patient characteristics, while the automated feedback process maintains ease of operation without requiring manual intervention for each parameter adjustment.

Inventive Principle:
Principle #23Feedback

3Measurement precision

If personalized filtration parameters are determined for each patient, then the capture efficiency and purity of CTCs are improved, but the detection process becomes more complex and time-consuming

Engineering Contradiction:
Improvedetection sensitivity of CTCsVSAvoidtime for sample processing
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent performs rapid preliminary measurement of hemorheological parameters (viscosity, cell deformability) before filtration to enable personalized parameter selection. This quick pre-characterization allows determination of optimal capillary number and filtration conditions without significant time investment, achieving high detection sensitivity while minimizing additional processing time.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The system efficiently adjusts filtration parameters based on measured patient-specific properties, optimizing the capillary number for each individual. This targeted parameter adjustment achieves high CTC detection sensitivity with minimal time loss, as the parameter selection is guided by rapid hemorheological measurements rather than extensive trial-and-error procedures.

Inventive Principle:
Principle #35Parameter changes

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 efficient and personalized isolation of CTCs with high capture efficiency and purity, adaptable to individual variations in blood properties, improving detection sensitivity and specificity compared to existing methods.

Implementation Method 1

Though it is well accepted that CTCs are generally larger and less deformable than normal blood cells, by far most reports on these microfiltration systems only focus on size differences

Methodology Applied
Scientific EffectSize-based filtration: Filter (physical)

Implementation Method 2

measuring hemorheological parameters of the sample

Methodology Applied
Scientific EffectRheological measurement: Rheometer

Data Source

PatentUS11096612B2Methods of personalized microfiltration to detect cells from blood
Publication Date: 2021.08.24 THE HONG KONG UNIV OF SCI & TECH
  • US11096612B2 patent drawing
  • US11096612B2 patent drawing
  • US11096612B2 patent drawing

AI summary

The present application provides a Capillary number-based method of isolating circulating rare cells from a blood sample from a subject using filtration parameters determined based on the measurement of hemorheological parameters of the sample. The present application also provides a method for determining filtration parameters in a microfluidic elasto-filtration process for isolating circulating rare cells from a blood sample from a subject. The present application further provides a device for isolating circulating rare cells from a blood sample from a subject and a non-transitory computer storage medium for performing methods described in the present application.