Multi-Section Cytometer for Simultaneous Cell Phenotyping
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Solution Overview
Problem
Existing cell phenotyping techniques are limited to either mechanical or electrical properties, lacking multiparametric analysis that could enhance disease prognosis and diagnosis, as they fail to simultaneously measure undeformed cell diameter, surface charge, and stiffness.
Innovation Solution
A cytometer with multiple measurement sections and lock-in amplifiers measures undeformed cell diameter, surface charge, and stiffness by analyzing ripples produced as cells pass through channels of varying widths, using simultaneous equations to determine these properties from peak-to-peak amplitudes and times.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If single-parameter cell phenotyping techniques are used, then the measurement process is simple, but the phenotyping depth and diagnostic applicability are limited
Solution Approach 1:
The patent combines mechanical phenotyping (deformability cytometry) and electrical phenotyping (impedance cytometry) into a single integrated measurement system. Cells are subjected to both mechanical deformation in microchannels and electrical impedance measurement simultaneously, enabling multiparametric phenotyping that captures both mechanical and electrical properties of cells for comprehensive disease diagnosis
Solution Approach 2:
The measurement system is designed to perform multiple functions: mechanical deformation measurement, electrical impedance measurement, and integrated multiparametric analysis. This universal system can measure various cell properties including size, shape, elastic modulus, cytoplasmic viscosity, and electric permittivity within a single platform, eliminating the need for separate specialized devices
2Productivity
If mechanical and electrical properties are measured separately, then each measurement can be optimized independently, but the throughput and efficiency are reduced
Solution Approach 1:
The patent merges mechanical deformability measurement and electrical impedance measurement into a single integrated flow system. Cells flow through microchannels where they experience controlled mechanical deformation while passing through electromagnetic fields for impedance measurement, enabling simultaneous acquisition of both mechanical and electrical phenotypic data at high throughput
Solution Approach 2:
The system performs preliminary cell preparation and conditioning in a unified flow path before measurement. Cells are hydrodynamically focused and pre-positioned in the microchannel flow, ensuring optimal alignment and positioning before they enter the measurement zone where both mechanical and electrical properties are captured simultaneously, maximizing throughput
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
Enables simultaneous measurement of undeformed cell diameter, surface charge, and stiffness, providing a more comprehensive diagnostic/prognostic tool for cell classification.
Implementation Method 1
Known techniques of electrical cell phenotyping include impedance cytometry
Implementation Method 2
deformability cytometry which is based on microscopic imaging of cell deformation upon flow stresses in microchannels
Data Source
AI summary
A cytometer includes a plurality of measurement sections, each comprising first and second sidewalls and a base therebetween, the sidewalls and base defining a channel portion extending from an entrance to an exit; an electrode group arranged on the opposite sides of the base and part way between the entrance and exit, the electrode group comprising an upstream electrode, a centre electrode and a downstream electrode in the way of a trajectory between the entrance and exit, and in respective order; the measurement sections being connected together to form at least one measurement channel comprising a plurality of the channel portions connected together in series; and, a lock-in amplifier; the central electrode of each group connected to the excitation signal port of the lock-in amplifier, and the upstream and downstream electrodes connected to the voltage differential input ports of the lock-in amplifier.