Suspended Microchannel Resonator for Mass Cytometry

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Solution Overview

Problem

Current flow cytometry methods are expensive, bulky, and limited in accessibility due to high costs and reliance on optics, making them unsuitable for point-of-use applications and efficient counting of cells like CD4+ T lymphocytes, bacteria, and viruses.

Innovation Solution

A mass cytometry method using a suspended microchannel resonator that monitors resonant frequency changes to count cells, employing nanoparticles and adjusting solution density to enhance signal detection, allowing for a compact, low-cost, and handheld device capable of detecting cells and viruses with high precision.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional flow cytometry with optical readout is used, then cell counting capability is achieved, but device cost and complexity increase significantly

Engineering Contradiction:
Improvecell counting capabilityVSAvoidoptical system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces the optical detection system with a mass spectrometry-based detection system. Instead of using lasers and fluorescent detectors to measure cell properties, the invention uses mass spectrometry to directly measure the mass of cells and viral particles, thereby eliminating complex optical components while maintaining measurement precision for cell counting and viral load detection

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The invention changes the measurement parameter from optical properties (fluorescence intensity, light scattering) to mass properties (mass-to-charge ratio). This parameter transformation enables the use of mass spectrometry for cell analysis, fundamentally altering how cells are detected and counted while reducing device complexity

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If bench-top flow cytometers are used, then accurate cell counting is achieved, but portability and accessibility are limited

Engineering Contradiction:
Improvecell counting accuracyVSAvoiddevice portability
Core Design Contradiction:
Measurement precisionVSWeight of moving object

Solution Approach 1:

The patent segments the cell analysis function into discrete components that can be integrated into a compact platform. By separating the mass spectrometry core from bulky optical systems and integrating it with microfluidic sample handling, the invention creates a modular system that maintains counting accuracy while enabling portability for point-of-use applications

Inventive Principle:
Principle #1Segmentation

3Measurement precision

If nanoparticles are added to enhance cell mass signal, then detection sensitivity improves, but background signal and interference increase

Engineering Contradiction:
Improvedetection sensitivityVSAvoidbackground signal interference
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The invention applies local quality differentiation by using nanoparticles of specific masses (e.g., 10 nm gold nanoparticles with known mass) that bind selectively to target cells. This localized mass addition creates a distinct signal pattern that can be differentiated from background, improving detection sensitivity while minimizing interference through careful selection of nanoparticle properties

Inventive Principle:
Principle #3Local quality

4Measurement precision

If solution density is adjusted to match cell density, then nanoparticle attachment requirements are reduced, but solution preparation complexity increases

Engineering Contradiction:
Improvesignal detection efficiencyVSAvoidsolution preparation complexity
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent changes the physical parameter of solution density to match cell density, thereby reducing the mass difference between cells and surrounding medium. This parameter adjustment minimizes the number of nanoparticles needed for detection while maintaining signal clarity, balancing detection efficiency with preparation complexity

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

The method provides a cost-effective, portable solution for cell counting with high dynamic range and sensitivity, enabling new applications and improving accessibility for clinical and diagnostic purposes, particularly for CD4+ T lymphocyte counting and viral load measurement.

Implementation Method 1

The sample is transported through a suspended microchannel resonator, and the resonant frequency is monitored

Methodology Applied
Scientific EffectResonant frequency: Resonance

Implementation Method 2

material functionalized with affinity molecules for the at least one cell type

Methodology Applied
Scientific EffectAffinity binding: Adsorption

Implementation Method 3

A mass cytometry method using a suspended microchannel resonator that monitors resonant frequency changes to count cells

Methodology Applied
Scientific EffectMass-sensitive readout:

Data Source

PatentUS8722419B2Flow cytometry methods and immunodiagnostics with mass sensitive readout
Publication Date: 2014.05.13 MASSACHUSETTS INST OF TECH
  • US8722419B2 patent drawing
  • US8722419B2 patent drawing
  • US8722419B2 patent drawing

AI summary

Mass cytometry method. In one aspect, the method includes providing a sample having at least one cell type and mixing the sample with material such as nanoparticles functionalized with affinity molecules for the at least one cell type. The sample is transported through a suspended microchannel resonator to record a mass histogram and a cell count for the at least one cell type is determined from the histogram.