Isovolumetric Red Blood Cell Spheroidization via Acoustic Heating

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Solution Overview

Problem

Current hematology analyzers face challenges in achieving high throughput and precise analysis of blood cells without significant dilution or thermal-induced changes, particularly in maintaining cells in their original state for accurate imaging and analysis.

Innovation Solution

The use of a piezoelectric heating method to spherify cells isovolumetrically within an acoustic wave field, eliminating the need for hypotonic buffers and avoiding thermal changes, allowing for precise image analysis without staining or marking, and enabling cells to be brought into focus for high-resolution imaging.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Shape

If conventional heating methods (water bath) are used to spherify red blood cells, then spheroidization can be achieved, but thermal-induced changes and agglutination occur that alter cell morphology

Engineering Contradiction:
Improvecell spheroidizationVSAvoidthermal-induced changes and agglutination
Core Design Contradiction:
ShapeVSObject-affected harmful factors

Solution Approach 1:

The patent replaces thermal heating (water bath) with acoustic field heating using piezoelectric elements. The piezoelectric elements generate acoustic waves that heat the red blood cells isovolumetrically without causing thermal-induced changes or agglutination, thus achieving spheroidization while preserving cell morphology.

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

Solution Approach 2:

The patent changes the heating parameter from conventional thermal conduction (water bath) to acoustic wave-based heating via piezoelectric elements. This parameter change enables isovolumetric heating that achieves spheroidization without the harmful thermal effects associated with conventional methods.

Inventive Principle:
Principle #35Parameter changes

2Shape

If hypotonic buffers and cell membrane destabilizing agents are used for spheroidization, then red blood cells can be spherulized, but significant dilution occurs and cells are altered from native state

Engineering Contradiction:
Improvecell spheroidizationVSAvoidsample dilution
Core Design Contradiction:
ShapeVSQuantity of substance

Solution Approach 1:

The patent replaces chemical spheroidization methods (hypotonic buffers and membrane destabilizing agents) with acoustic field-based isovolumetric heating using piezoelectric elements. This substitution eliminates the need for significant sample dilution and preserves cells in a native-like state while achieving spheroidization.

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

3Measurement precision

If high magnification optical microscopy is used to image cells, then resolution is improved, but depth of field becomes too shallow to capture entire cell depth

Engineering Contradiction:
Improveimage resolutionVSAvoiddepth of field
Core Design Contradiction:
Measurement precisionVSLength of stationary object

Solution Approach 1:

The patent applies preliminary acoustic field heating to spherulize red blood cells before optical imaging. This preliminary action transforms the biconcave cells into spherical shapes with uniform thickness, ensuring that the entire cell depth falls within the shallow depth of field of high-magnification objective lenses, thereby enabling complete cell imaging at high resolution.

Inventive Principle:
Principle #10Preliminary action

4Shape

If conventional heating to spherulize cells is performed, then spheroidization occurs, but overheating causes protein agglutination and morphological changes

Engineering Contradiction:
Improvecell spheroidizationVSAvoidcell morphology preservation
Core Design Contradiction:
ShapeVSManufacturing precision

Solution Approach 1:

The patent replaces conventional thermal heating with acoustic wave-based heating using piezoelectric elements. This substitution enables precise isovolumetric heating that achieves spheroidization without overheating, thereby preventing protein agglutination and preserving cell morphology.

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

Solution Approach 2:

The patent changes the heating mechanism from thermal conduction to acoustic wave heating, which provides more uniform and controllable temperature distribution. This parameter change prevents localized overheating and protein agglutination while achieving the desired spheroidization and morphology preservation.

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 allows for efficient, high-throughput analysis of blood cells with minimal dilution and thermal impact, maintaining cells in a native-like state for precise volume determination and imaging, avoiding agglutination and morphological changes, thus enhancing analytical accuracy.

Implementation Method 1

an acoustic wave field is generated by means of a piezo element operated with a voltage and a frequency, and wherein the cell is located in the wave field and is heated by the wave field

Methodology Applied
Scientific EffectAcoustic wave field heating: Ultrasonic Vibration

Implementation Method 2

a piezo element operated by applying a voltage and a frequency and thereby generates an acoustic wave field

Methodology Applied
Scientific EffectPiezoelectric effect: Piezoelectric Effect

Data Source

PatentEP3647767B1Isovolumetric balling of red blood cells
Publication Date: 2024.09.25 SIEMENS HEALTHINEERS AG
  • EP3647767B1 patent drawingFigure 1~2
  • EP3647767B1 patent drawingFigure 3~4

AI summary

The invention relates to an automatic analyzer for analyzing a medical sample, the analyzer comprising an analysis cell for the sample, a piezoelectric element and an analysis device, wherein the piezoelectric element can be operated by applying a voltage and a frequency and thereby generates an acoustic wave field, wherein a sample located in the analysis cell is in the acoustic wave field when the piezoelectric element is operated.