Automated Sample Preparation for Flow Cytometry Concentration Control

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Solution Overview

Problem

Current flow cytometry methods require significant labor for accurately determining the mixing ratio of samples and detection reagents, and preparing measurement samples for multi-color analysis, especially for low-abundance antigens like stem cells, due to the need for precise concentration adjustments and multiple reagent combinations.

Innovation Solution

A sample preparation apparatus and method that includes a measurement unit, a sample preparation unit, and a control unit to automatically generate concentration information of measurement target particles, adjust reagent amounts, and prepare samples by mixing particles with appropriate fluorescently labeled antibodies, optimizing the concentration and number of samples for analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If manual determination of mixing ratio and sample amount is performed by examiner, then flexibility in adjusting reagent amounts is maintained, but labor intensity and time consumption increase significantly

Engineering Contradiction:
Improvemanual adjustment flexibilityVSAvoidlabor time for sample preparation
Core Design Contradiction:
Ease of operationVSLoss of time

Solution Approach 1:

The system performs self-adjustment of sample and reagent amounts based on automated particle concentration measurement. The control unit automatically calculates and dispenses appropriate volumes without requiring manual intervention, making the system self-sufficient in the sample preparation process

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

Manual mechanical operations for measuring and mixing are replaced by an automated control system that uses electronic sensors, processors, and dispensing mechanisms to perform the same functions with higher precision and without labor

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

2Adaptability or versatility

If multiple reagent combinations are used for multi-color analysis, then detection capability for multiple antigens is improved, but complexity of sample preparation increases

Engineering Contradiction:
Improvemulti-antigen detection capabilityVSAvoidsample preparation complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The control unit is designed to universally handle multiple reagent types and analysis modes through a single integrated system. It automatically identifies the required reagent combination based on the analysis type and performs all necessary preparations through standardized automated procedures, making the system adaptable to various detection requirements without increasing operational complexity

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

Solution Approach 2:

The sample preparation process is divided into distinct automated steps: particle concentration measurement, calculation of required amounts, and automated dispensing. This segmentation allows the system to handle multiple reagent combinations through a series of standardized modular operations rather than complex manual procedures

Inventive Principle:
Principle #1Segmentation

3Measurement precision

If concentration of measurement target particles is adjusted manually, then accuracy of detection for low-abundance antigens is improved, but precision of concentration adjustment decreases

Engineering Contradiction:
Improvedetection accuracy for low-abundance antigensVSAvoidconcentration adjustment precision
Core Design Contradiction:
Measurement precisionVSManufacturing precision

Solution Approach 1:

The system uses a feedback loop where particle concentration is first measured by the particle analyzer, then this measurement information is fed back to the control unit to calculate the precise amount of sample and reagent needed. This closed-loop feedback ensures accurate concentration adjustment based on actual measured values rather than manual estimation

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

Manual concentration adjustment is replaced by automated electronic control that uses precise electronic dispensing mechanisms driven by calculated values from the particle concentration measurement, achieving higher precision than manual mechanical operations

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

4Reliability

If sample amount is increased to detect low-abundance stem cells, then detection reliability is improved, but total volume of sample required increases

Engineering Contradiction:
Improvedetection reliability for stem cellsVSAvoidtotal sample volume required
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The system changes the concentration parameter of the sample through automated adjustment. By measuring initial particle concentration and calculating the appropriate dilution or concentration factor, the system optimizes the final sample concentration to ensure sufficient target particles are present for reliable detection while minimizing the total volume required

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 efficiently prepares measurement samples with high accuracy, reducing labor and improving the efficiency of flow cytometric analysis by automating the concentration adjustment and reagent mixing process, enabling precise detection of target antigens even at low abundance.

Implementation Method 1

detect the stained cells by an optical detection method

Methodology Applied
Scientific EffectOptical detection: Absorption Spectroscopy

Implementation Method 2

prepare a measurement sample by mixing a sample and any of a plurality of types of particle detection reagents including a particle labeling substance

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS11971342B2Sample preparation apparatus, sample preparation system, sample preparation method, and particle analyzer
Publication Date: 2024.04.30 SYSMEX CORP
  • US11971342B2 patent drawing
  • US11971342B2 patent drawing
  • US11971342B2 patent drawing

AI summary

The sample preparation apparatus includes a measurement unit configured to measure a sample containing particles acquired from a sample container and detect measurement target particles in the sample, a sample preparation unit capable of adjusting the concentration of measurement target particles in a sample acquired from a sample container and configured to prepare a measurement sample by mixing a sample and any of a plurality of types of particle detection reagents including a particle labeling substance, and a control unit for controlling the sample preparation unit so as to generate concentration information of the measurement target particles in the sample in the sample container based on the measurement data of the measurement unit and adjust the concentration of the measurement target particles in the sample acquired from the sample container according to the generated concentration information and the type of particle detection reagent used for preparing the measurement sample.