Spectrum Measuring Device for Direct Cellular Metabolic State Analysis

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Solution Overview

Problem

Existing methods for measuring the metabolic state of cells in bio-processes are prone to contamination, labor-intensive, and provide indirect results, as they measure the culture solution rather than the cells directly, making it difficult to determine if cells are utilizing resources like glucose for energy.

Innovation Solution

A spectrum measuring device and method that irradiates a culture solution with excitation light, receives fluorescence, and calculates the fluorescence spectrum of cells by subtracting the medium's spectrum, allowing for precise measurement of the metabolic state of cells through autofluorescence analysis, minimizing the impact of internal shields and medium interference.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If sampling method is used to measure metabolic state, then measurement can be performed, but contamination risk increases and measurement time increases

Engineering Contradiction:
Improvemeasurement accuracyVSAvoidmeasurement time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent replaces the mechanical sampling process with an optical measurement system. Instead of physically removing samples for analysis, the system uses fluorescence spectroscopy to measure metabolic state directly in the bioreactor, eliminating contamination risks and time losses associated with sampling while maintaining measurement accuracy.

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

2Ease of operation

If culture solution is measured instead of direct cell measurement, then measurement process is simplified, but measurement precision decreases as results are indirect

Engineering Contradiction:
Improvemeasurement simplicityVSAvoidmetabolic state measurement accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent applies local quality by selectively measuring fluorescence from cells rather than the entire culture solution. By using spectral subtraction to remove medium fluorescence and focusing on cell-specific fluorescence signals, the system achieves both operational simplicity and high measurement precision for cellular metabolic state.

Inventive Principle:
Principle #3Local quality

3Quantity of substance

If deep fluorescence region is measured, then more cellular information is obtained, but internal shield increases reducing measurement accuracy

Engineering Contradiction:
Improvefluorescence signal amountVSAvoidfluorescence spectrum accuracy
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The patent extracts the harmful internal shield effect through spectral subtraction. By measuring the fluorescence spectrum of the medium separately and subtracting it from the culture solution spectrum, the system removes the medium's contribution and isolates the cellular fluorescence signal, thereby eliminating the internal shield problem while maintaining adequate signal quantity.

Inventive Principle:
Principle #2Taking out (Extraction)

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 accurate, direct measurement of cellular metabolic states, reducing labor and contamination risks, and allowing for in-line analysis without sampling, thereby improving process control and resource utilization assessment.

Implementation Method 1

a light source device for irradiating a first surface of the space with excitation light, a light receiving device for receiving fluorescence occurring from the first surface

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

the arithmetic device calculates the fluorescence spectrum of the cells by subtracting the fluorescence spectrum of the medium from the spectrum of the fluorescence of the culture solution

Methodology Applied
Scientific EffectSpectral subtraction:

Data Source

PatentUS11391630B2Spectrum measuring device and spectrum measuring method
Publication Date: 2022.07.19 AZBIL CORP
  • US11391630B2 patent drawing
  • US11391630B2 patent drawing
  • US11391630B2 patent drawing

AI summary

A spectrum measuring device according to the present disclosure includes an accommodation part having a space for accommodating a culture solution containing a medium and cells, a light source device for irradiating a first surface of the space with excitation light, a light receiving device for receiving fluorescence occurring from the first surface, and an arithmetic device for spectral analysis of the fluorescence received by the light receiving device. In the space, the depth from the first surface of a fluorescence region where fluorescence is produced by incident excitation light is a value giving an internal shield of a prescribed level of less in the fluorescence region. The arithmetic device calculates the fluorescence spectrum of the cells by subtracting the fluorescence spectrum of the medium from the spectrum of the fluorescence of the culture solution obtained by the light receiving device.