CELIF Spectroscopy for Breath Acetone Quantification

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Solution Overview

Problem

Current methods for diagnosing and monitoring diabetes-related ketoacidosis, particularly in children and pregnant women, face challenges due to invasive blood sampling, inaccurate ketone measurements, and the need for timely and accurate detection of acetone levels in exhaled breath, which is complicated by the presence of other gases and high selectivity requirements.

Innovation Solution

The use of Cavity-Enhanced Laser-Induced Fluorescence (CELIF) spectroscopy, which combines cavity ring-down spectroscopy and laser-induced fluorescence to provide a non-invasive, portable, and real-time measurement of acetone concentration in exhaled breath, overcoming limitations of sensitivity, selectivity, and portability in existing techniques.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional blood sampling methods are used for ketone measurement, then measurement accuracy can be achieved, but invasive procedures and sampling difficulty increase

Engineering Contradiction:
Improveketone measurement accuracyVSAvoidsampling difficulty
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent replaces invasive mechanical blood sampling with non-invasive breath analysis. Instead of drawing blood to measure ketones, the system analyzes acetone in exhaled breath using optical detection, eliminating the need for needles, tubes, and laboratory processing while maintaining measurement capability.

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

Solution Approach 2:

The patent uses acetone in breath as an intermediary marker to indirectly measure ketone levels. Rather than directly measuring ketones in blood, the system detects acetone which correlates with ketone body breakdown, providing a convenient proxy that avoids invasive sampling while maintaining diagnostic accuracy.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If blood pH measurement is used to monitor DKA response, then treatment monitoring can be performed, but results may be masked by hypochloraemia and timing is delayed

Engineering Contradiction:
Improvetreatment monitoring accuracyVSAvoidresult reporting delay
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent replaces laboratory-based blood pH measurement with portable breath acetone analysis. The system uses optical detection in a handheld device that provides immediate results at the point of care, eliminating the need for sample transport, laboratory processing, and delayed result reporting.

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

Solution Approach 2:

The patent enables self-service monitoring at the point of care. The portable device allows healthcare providers to immediately measure breath acetone levels during treatment without requiring referral to a laboratory, providing real-time feedback that guides treatment decisions without delay.

Inventive Principle:
Principle #25Self-service

3Manufacturing precision

If laser spectroscopic techniques are used for breath analysis, then selectivity can be improved, but sensitivity for very low concentrations remains difficult to achieve

Engineering Contradiction:
Improvegas selectivityVSAvoidacetone detection sensitivity
Core Design Contradiction:
Manufacturing precisionVSMeasurement precision

Solution Approach 1:

The patent combines multiple laser spectroscopic techniques (cavity ring-down spectroscopy and laser-induced fluorescence) into a hybrid system. This merging of methods allows the system to leverage the high selectivity of CRDS while using LIF enhancement to achieve the sensitivity needed for detecting very low acetone concentrations in breath.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent optimizes detection parameters including laser wavelength, cavity length, and detection sensitivity to simultaneously achieve high selectivity and sensitivity. By carefully selecting the laser wavelength to match acetone absorption features and optimizing the optical cavity parameters, the system achieves both gas-specific detection and low-concentration sensitivity.

Inventive Principle:
Principle #35Parameter changes

4Ease of operation

If point-of-care portable devices are developed, then ease of operation and real-time measurement are improved, but device complexity and cost increase

Engineering Contradiction:
Improveportability and real-time measurementVSAvoidinstrumentation complexity
Core Design Contradiction:
Ease of operationVSDevice complexity

Solution Approach 1:

The patent merges the optical detection system with portable breath sampling capabilities into a single integrated device. The handheld unit combines the laser source, optical cavity, detection electronics, and breath sampling interface in one portable package, eliminating the need for separate laboratory equipment while maintaining measurement capability.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent designs a universal platform that can monitor multiple breath biomarkers including acetone, formaldehyde, and hydrogen cyanide using the same optical detection system. This multi-functional design allows a single device to track different metabolic states and disease conditions, justifying the investment in portable technology through versatile clinical application.

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

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

CELIF enables accurate, absolute, and real-time quantification of acetone in breath, facilitating timely and confident treatment decisions, reducing uncertainty and improving diabetes management by providing a reliable point-of-care solution.

Implementation Method 1

Cavity ring-down spectroscopy (CRDS) measures the absorption of light by the sample. CRDS is implemented by injecting a laser pulse into a stable optical cavity consisting of two highly reflective mirrors.

Methodology Applied
Scientific EffectCavity ring-down spectroscopy: Absorption (EM radiation)

Implementation Method 2

Laser-induced fluorescence (LIF) is an indirect detection technique. When an analyte molecule absorbs light it is excited into a higher energy state. This excited molecule can release its energy by emitting light (fluorescence) that is detected by a photodetector

Methodology Applied
Scientific EffectLaser-induced fluorescence: Fluorescence

Data Source

PatentEP3331428B1Determination of acetone in breath by fluorescence analysis
Publication Date: 2024.06.19 UNIVERSITY OF DURHAM
  • EP3331428B1 patent drawingFigure 1a
  • EP3331428B1 patent drawingFigure 1b
  • EP3331428B1 patent drawingFigure 2

AI summary

A method and apparatus for quantifying an analyte in a gas phase or liquid sample comprises: a pulsed or continuous, coherent or incoherent light source (10), a pair of reflective mirrors (13) located on the optical axis forming an optical cavity, and a cell (4) located between the mirrors (13), the cell (4) having a gas inlet (3) and a gas outlet (5); a fluorescence detector (17) located off the cavity axis and arranged to provide a first signal in response to fluorescence within the cavity; a photon detector (14) located axially external to the cavity and arranged to provide a second signal; wherein the apparatus including the axial photon detector (14) is configured to comprise a cavity enhanced absorption spectrometer; wherein apparatus including the off-axis photon detector is configured to comprise a cavity-enhanced laser-induced fluorescence (CELIF) spectrophotometer; means for supplying a pure sample or an analyte-containing sample to the cavity; a processor (9) adapted to receive a first signal to calibrate the apparatus and to receive a second signal to provide a measurement of the concentration of the analyte in the sample.