Massive Microfluidics Multiplexed CTC Counting

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Solution Overview

Problem

Current microfluidic devices face challenges in efficiently detecting and counting rare circulating tumor cells (CTCs) due to low assay throughput, high costs, and the need for extensive detection hardware, which is not feasible with large numbers of microfluidic channels.

Innovation Solution

The implementation of a massive microfluidic technique that reduces assay time through label-free multiplexed surface marker detection using transit-time analysis in ultra-high-throughput flow cytometry, allowing for efficient detection and sorting of CTCs with a significantly reduced number of electronic channels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If the number of microfluidic channels is increased to improve CTC detection throughput, then assay throughput is improved, but detection hardware complexity and cost increase

Engineering Contradiction:
Improveassay throughputVSAvoiddetection hardware complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

Multiple microfluidic channels share a common detection zone and detection electronics. The patent integrates several channels into a single detection region where cells from different channels are simultaneously analyzed by shared electronic components, eliminating the need for separate detectors per channel.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The detection electronics serve multiple functions by analyzing cells from multiple channels simultaneously. A single detection system performs the work of multiple independent detectors, providing universal detection capability across all microfluidic channels through time-multiplexed or spatial-multiplexed approaches.

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Measurement precision

If traditional detection methods are used for rare CTCs, then detection sensitivity is improved, but assay time increases

Engineering Contradiction:
Improvedetection sensitivityVSAvoidassay time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

Cells are pre-focused and concentrated into a narrow stream before entering the detection zone using hydrodynamic focusing or inertial forces. This preliminary action ensures that rare CTCs are positioned optimally for detection, increasing detection sensitivity without requiring longer assay times.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The system uses periodic sampling or time-multiplexed detection where cells are detected in rapid sequential intervals. This allows high-throughput analysis maintaining sensitivity by ensuring each cell receives adequate detection time while processing large numbers of cells efficiently.

Inventive Principle:
Principle #19Periodic action

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 high sensitivity, specificity, and multiplexed surface marker detection with reduced assay time and cost, achieving a more efficient design by dramatically increasing the number of microfluidic channels while minimizing detection hardware requirements.

Implementation Method 1

transit-time analysis in ultra-high-throughput flow cytometry

Methodology Applied
Scientific EffectTransit-time analysis:

Implementation Method 2

the use of dielectrophoresis (DEP) actuation to enhance cellular interaction with surface coated antibodies or other types of molecular recognition molecules

Methodology Applied
Scientific EffectDielectrophoresis (DEP):

Implementation Method 3

electrical impedance sensors

Methodology Applied
Scientific EffectElectrical impedance: Electrical Impedance Tomography

Data Source

PatentUS11266984B2Massive microfluidics for multiplexed counting
Publication Date: 2022.03.08 THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
  • US11266984B2 patent drawing
  • US11266984B2 patent drawing
  • US11266984B2 patent drawing

AI summary

A microfluidics device includes an inlet, a plurality of parallelized microfluidic channels, a splitter and a plurality of detection electrodes. The inlet receives a fluidic sample including biological particles. The parallelized microfluidic channels include interaction zones for analysis of the biological particles. The splitter transmits the fluidic sample into the parallelized microfluidic channels. Detection electrodes can conduct the analysis. Each detection electrode is shared among the parallelized microfluidic channels. The detection electrodes are spatially encoded electrodes arranged on locations of each of the parallelized microfluidic channels.