Harmonics Microscope Single RBC HbA1c Measurement

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Solution Overview

Problem

Current methods for measuring glycated hemoglobin fractions are limited by the need for large blood samples, inability to perform non-invasive measurements, and inability to resolve glucose fluctuations at the level of a single red blood cell, leading to misdiagnosis and limitations in monitoring diabetes complications.

Innovation Solution

A harmonics microscope system that uses a laser device, upright microscope, light splitter, and optical detector to measure glycated hemoglobin fractions of a single red blood cell through non-invasive means, generating multispectral images for accurate in vitro or in vivo analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional glycated hemoglobin measurement methods are used, then average blood glucose level can be evaluated, but measurement resolution at single red blood cell level cannot be achieved

Engineering Contradiction:
Improvemeasurement resolutionVSAvoidmeasurement system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the measurement process by isolating and measuring individual red blood cells separately rather than measuring bulk blood samples. The flow cell device enables single-cell suspension and sequential measurement, achieving single-cell resolution by dividing the measurement task into discrete cellular units

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces a flow cell device as an intermediary component that suspends single red blood cells and directs them through the measurement zone. This intermediary enables the transition from bulk measurement to single-cell measurement by providing a controlled environment for individual cell analysis

Inventive Principle:
Principle #24Intermediary (Mediator)

2Quantity of substance

If large blood samples are used for measurement, then sufficient material for analysis is obtained, but non-invasive measurement becomes impossible

Engineering Contradiction:
Improveblood sample volumeVSAvoidinvasiveness
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent extracts the essential measurement function from bulk blood analysis by measuring only the glycated hemoglobin content of individual red blood cells. This extraction approach reduces the required blood sample volume from milliliters to microliters, enabling minimally invasive or non-invasive measurement while maintaining analytical capability

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the measurement parameter from bulk average concentration to single-cell glycated hemoglobin fraction. By measuring the HbA1c fraction in individual cells rather than averaging across large blood volumes, the system achieves accurate diabetes monitoring with minimal blood sample requirements

Inventive Principle:
Principle #35Parameter changes

3Loss of information

If average glycated hemoglobin from large blood samples is measured, then overall glucose level is obtained, but glucose fluctuation information is lost

Engineering Contradiction:
Improveglucose fluctuation informationVSAvoidmeasurement throughput
Core Design Contradiction:
Loss of informationVSProductivity

Solution Approach 1:

The patent segments the blood sample into individual red blood cells and measures each cell's glycated hemoglobin content separately. This segmentation preserves information about individual cell variations that reflect glucose fluctuations, whereas bulk measurement averages out these variations and loses the fluctuation data

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent measures glycated hemoglobin in a subset of individual red blood cells rather than analyzing all cells in large blood volumes. By measuring hundreds of individual cells, the system obtains sufficient statistical data to characterize glucose patterns while maintaining high measurement throughput and preserving fluctuation information

Inventive Principle:
Principle #16Partial or excessive action

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 precise measurement of glycated hemoglobin fractions at the single red blood cell level, reducing misdiagnosis rates and providing detailed glucose fluctuation data without the need for large blood samples, thus improving diabetes diagnosis and monitoring.

Implementation Method 1

the laser device emits laser beams of different wavelengths; each of the laser beams has a central wavelength and a frequency to specifically optimize optical characteristics of glycated hemoglobin for measure the HbA1c fraction

Methodology Applied
Scientific EffectLaser: Laser

Implementation Method 2

the light splitter divides the harmonic observing beams into a first third harmonic generation (THG) segment, a second THG segment, a third THG segment, and a second harmonic generation (SHG) segment

Methodology Applied
Scientific EffectThird harmonic generation:

Implementation Method 3

the light splitter divides the harmonic observing beams into a first third harmonic generation (THG) segment, a second THG segment, a third THG segment, and a second harmonic generation (SHG) segment

Methodology Applied
Scientific EffectSecond harmonic generation: Second Harmonic Generation

Implementation Method 4

the optical detector receives the first THG segment, the second THG segment, the third THG segment, and the SHG segment from the light splitter; the optical detector detects the first THG segment, the second THG segment, the third THG segment, and the SHG segment to be converted into a first THG image signal, a second THG image signal, a third THG image signal, and an SHG image signal

Methodology Applied
Scientific EffectPhotoelectric detection: Photoelectric Effect

Data Source

PatentUS12188862B2Harmonics microscope for measuring glycated hemoglobin fraction of single red blood cell
Publication Date: 2025.01.07 NAT TAIWAN UNIV
  • US12188862B2 patent drawing
  • US12188862B2 patent drawing
  • US12188862B2 patent drawing

AI summary

A microscope is provided to measure HbA1c fraction. The microscope measures the HbA1c fraction of a single red blood cell (RBC) in a trace blood sample. The HbA1c fraction can be measured through a non-invasive way while the RBC flows in a human epidermal microvessel, too. The microscope comprises a laser device, an upright microscope, a light splitter, a light detector, and a mainframe. Unlike traditional methods, the HbA1c fraction can be measured in vitro or in vivo at the level of a single RBC. Accurate measurement is achieved. Misdiagnosis rate is reduced. The microscope provides HbA1c fractions from hundreds of RBCs, instead of averaging HbA1c fractions obtained from a large number of blood samples. Hence, the present invention is a method of detecting a HbA1c fraction of a single RBC, and is a microscope supporting blood-drawing measurement and non-invasive measurement simultaneously.