Sample Transfer Apparatus for Mass Cytometry

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Solution Overview

Problem

Existing methods for transferring particles in a sample for mass cytometry, particularly those involving elemental tagged cells or beads suspended in an aqueous solution, face challenges such as droplet agglomeration and signal abnormalities due to high velocity sprays and thermal effects, which affect the accuracy and integrity of particle analysis.

Innovation Solution

A decelerator tube and elongate accelerator chamber system that decelerates and then accelerates the sample spray using a sheath gas, reducing droplet size and promoting recirculation to minimize agglomeration and thermal disruptions, while maintaining particle integrity and focusing for precise mass analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If a high velocity spray is used to transfer particles to ICP, then transfer efficiency is improved, but droplet agglomeration and signal abnormalities occur

Engineering Contradiction:
Improvetransfer efficiencyVSAvoidsignal quality
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The transfer process is divided into distinct stages: a deceleration zone where high velocity spray is slowed down, and an acceleration zone where particles are re-accelerated toward the ICP. This segmentation allows the spray to be decelerated to prevent agglomeration during transfer, then re-accelerated to maintain transfer efficiency, resolving the contradiction between transfer efficiency and signal quality

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

A sheath gas flow is introduced as an intermediary medium between the sample spray and the ICP. The sheath gas carries the decelerated particles through the transfer interface, providing a controlled environment that prevents droplet agglomeration while maintaining particle integrity and signal quality

Inventive Principle:
Principle #24Intermediary (Mediator)

2Manufacturing precision

If thermal effects are applied to reduce droplet size, then spray drying is improved, but particle integrity is compromised

Engineering Contradiction:
Improvedroplet size controlVSAvoidparticle integrity
Core Design Contradiction:
Manufacturing precisionVSStability of the object's composition

Solution Approach 1:

Thermal drying methods are replaced with a mechanical/aerodynamic approach using controlled gas flows. The sheath gas provides mechanical drying and particle transport without the thermal stress that would compromise particle integrity, achieving droplet size control through aerodynamic forces rather than thermal effects

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

3Reliability

If droplet recirculation is implemented, then agglomeration is reduced, but transfer time increases

Engineering Contradiction:
Improvedroplet separationVSAvoidtransfer time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The transfer interface is segmented into a deceleration zone where recirculation occurs to prevent agglomeration, and a separate acceleration zone that quickly propels particles toward the ICP. This segmentation allows recirculation to occur only where needed for droplet separation, while minimizing the time particles spend in the system overall

Inventive Principle:
Principle #1Segmentation

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 system effectively decelerates and accelerates the sample spray, enhancing particle separation and analysis accuracy, as evidenced by lower coefficient of variation in particle detection and improved signal quality compared to prior art methods.

Implementation Method 1

The acceleration channel and the outlet end can have a configuration to form a pressure reduction through the outlet end, so as to accelerate the sheath gas, and along with it the emerging decelerated sample spray, through the outlet end

Methodology Applied
Scientific EffectPressure drop: Pressure Drop

Implementation Method 2

an inductively coupled plasma for ionizing the accelerated sample spray of dispersion of particles

Methodology Applied
Scientific EffectIonization: Ionisation

Implementation Method 3

a nebulizer, for example, a pneumatic assisted nebulizer, for generating a sample spray of dispersion of particles

Methodology Applied
Scientific EffectNebulization:

Data Source

PatentEP2771667B1Sample transferring apparatus for mass cytometry
Publication Date: 2017.01.04 FLUIDIGM CANADA INC
  • EP2771667B1 patent drawingFigure 1
  • EP2771667B1 patent drawingFigure 2A~2B
  • EP2771667B1 patent drawingFigure 3

AI summary

In a mass cytometer or mass spectrometer, a sample of elemental tagged particles is transferred from a dispersion to a gas flow through a carrier aerosol spray for atomization and ionization by inductively coupled plasma (ICP) source. The configuration of the sample transfer apparatus allow for total consumption of the sample by passing the sample spray through a deceleration stage to decelerate the spray of particles from its high velocity expansion. Following the deceleration stage, the decelerated sample of particles can be accelerated and focused through an acceleration stage for transferring into the ICP. This effectively improves the particle transfer between the sample spray and the ICP.