Chuji Wang

Breath Analysis Using Laser Spectroscopic Techniques: Breath Biomarkers, Spectral Fingerprints, and Detection Limits

Breath analysis, a promising new field of medicine and medical instrumentation, potentially offers noninvasive, real-time, and point-of-care (POC) disease diagnostics and metabolic status monitoring. Numerous breath biomarkers have been detected and quantified so far by using the GC-MS technique. Recent advances in laser spectroscopic techniques and laser sources have driven breath analysis to new heights, moving from laboratory research to commercial reality. Laser spectroscopic detection techniques not only have high-sensitivity and high-selectivity, as equivalently offered by the MS-based techniques, but also have the advantageous features of near real-time response, low instrument costs, and POC function. Of the approximately 35 established breath biomarkers, such as acetone, ammonia, carbon dioxide, ethane, methane, and nitric oxide, 14 species in exhaled human breath have been analyzed by high-sensitivity laser spectroscopic techniques, namely, tunable diode laser absorption spectroscopy (TDLAS), cavity ringdown spectroscopy (CRDS), integrated cavity output spectroscopy (ICOS), cavity enhanced absorption spectroscopy (CEAS), cavity leak-out spectroscopy (CALOS), photoacoustic spectroscopy (PAS), quartz-enhanced photoacoustic spectroscopy (QEPAS), and optical frequency comb cavity-enhanced absorption spectroscopy (OFC-CEAS). Spectral fingerprints of the measured biomarkers span from the UV to the mid-IR spectral regions and the detection limits achieved by the laser techniques range from parts per million to parts per billion levels. Sensors using the laser spectroscopic techniques for a few breath biomarkers, e.g., carbon dioxide, nitric oxide, etc. are commercially available. This review presents an update on the latest developments in laser-based breath analysis.

A Study on Breath Acetone in Diabetic Patients Using a Cavity Ringdown Breath Analyzer: Exploring Correlations of Breath Acetone With Blood Glucose and Glycohemoglobin A1C

Acetone is qualitatively known as a biomarker of diabetes; however, the quantitative information on acetone concentration in diabetic breath is incomplete, and the knowledge of correlations of breath acetone with diabetic diagnostic parameters, namely, blood glucose (BG) and glycohemoglobin A1C (A1C), are unknown. We utilized a pilot-scale breath acetone analyzer based on the cavity ringdown spectroscopy (CRDS) technique to conduct breath tests with 34 Type 1 diabetic (T1D), ten Type 2 diabetic (T2D) patients, and 15 apparently healthy individuals. Relations between breath acetone and BG, A1C, and several other bio indices, such as the type of diabetes, onset-time, gender, age, and weight were investigated. Our observations show that a linear correlation between the mean group acetone and the mean group BG level does exist (R = 0.98, P < 0.02) when all the T1D subjects tested are grouped by different BG levels, 40-100, 101-150, 151-200, and 201-419 mg/dL. Similarly, among the T1D subjects studied, when their A1Cs are grouped by < 7, 7-9.9, and 10-13, a linear correlation between the mean group A1C and the mean group acetone concentration is observed (R = 0.98, P < 0.02). No strong correlations are observed when the BG and A1C numbers are not grouped. The mean breath acetone concentration in the T1D subjects studied in this work is determined to be 2.19 ppmv (parts per million by volume), which is higher than the mean breath acetone concentration, 0.48 ppmv, in the 15 healthy people tested.

Fiber ringdown pressure sensors

An exploratory study on a novel fiber ringdown pressure sensor is presented. With this technique, pressure measurements are achieved in a time domain by measurement of ringdown times. The proof-of-concept device consists of a diode laser light source, two 2 x 1 fiber couplers, a section of fused-silica single-mode fiber, a photodetector, and an electronic control. The sensors performance in the areas of stability, repeatability, and dynamic range is explored. The results demonstrate the new concept of fiber pressure sensors and the technical feasibility of developing a new generation of fiber sensors for pressure measurements.

Fiber loop ringdown for physical sensor development: pressure sensor.

A new method of developing optical fiber pressure sensors by use of a fiber loop ringdown scheme is described. The fiber loop ringdown system is characterized in terms of the ringdown baseline stability, fiber transmission loss, and fiber refractive index. The overall sensor performance is demonstrated by use of sensing forces applied to the sensor head. The current device can sense pressures in the range of 0 to 9.8 x 10(6) Pa, converted approximately from the applied forces. The sensors linear response, repeatability, detection sensitivity, measuring dynamic range, and temperature tolerance are explored.

Fiber Loop Ringdown — a Time-Domain Sensing Technique for Multi-Function Fiber Optic Sensor Platforms: Current Status and Design Perspectives

Fiber loop ringdown (FLRD) utilizes an inexpensive telecommunications light source, a photodiode, and a section of single-mode fiber to form a uniform fiber optic sensor platform for sensing various quantities, such as pressure, temperature, strain, refractive index, chemical species, biological cells, and small volume of fluids. In FLRD, optical losses of a light pulse in a fiber loop induced by changes in a quantity are measured by the light decay time constants. FLRD measures time to detect a quantity; thus, FLRD is referred to as a time-domain sensing technique. FLRD sensors have near real-time response, multi-pass enhanced high-sensitivity, and relatively low cost (i.e., without using an optical spectral analyzer). During the last eight years since the introduction of the original form of fiber ringdown spectroscopy, there has been increasing interest in the FLRD technique in fiber optic sensor developments, and new application potential is being explored. This paper first discusses the challenging issues in development of multi-function, fiber optic sensors or sensor networks using current fiber optic sensor sensing schemes, and then gives a review on current fiber optic sensor development using FLRD technique. Finally, design perspectives on new generation, multi-function, fiber optic sensor platforms using FLRD technique are particularly presented.

An acetone breath analyzer using cavity ringdown spectroscopy: an initial test with human subjects under various situations

We have developed a portable breath acetone analyzer using cavity ringdown spectroscopy (CRDS). The instrument was initially tested by measuring the absorbance of breath gases at a single wavelength (266 nm) from 32 human subjects under various conditions. A background subtraction method, implemented to obtain absorbance differences, from which an upper limit of breath acetone concentration was obtained, is described. The upper limits of breath acetone concentration in the four Type 1 diabetes (T1D) subjects, tested after a 14 h overnight fast, range from 0.80 to 3.97 parts per million by volume (ppmv), higher than the mean acetone concentration (0.49 ppmv) in non-diabetic healthy breath reported in the literature. The preliminary results show that the instrument can tell distinctive differences between the breath from individuals who are healthy and those with T1D. On-line monitoring of breath gases in healthy people post-exercise, post-meals and post-alcohol-consumption was also conducted. This exploratory study demonstrates the first CRDS-based acetone breath analyzer and its potential application for point-of-care, non-invasive, diabetic monitoring.

High-sensitivity fiber-loop ringdown evanescent-field index sensors using single-mode fiber

We combine the evanescent-field scattering sensing mechanism with the fiber-loop ringdown detection scheme to create a new type of fiber optic index sensor using partially cladded single-mode fiber as a sensing element. A detection limit for an optical index change of 3.2x10(-5) is demonstrated in the initial examination by using certified refractive index oils and laboratory-made sodium chloride solutions. This is the highest sensitivity for a fiber optic index sensor to date (to our knowledge) without using any chemical coating, delicate fiber components, and/or sophisticated architecture at the sensor head. A potential detection limit can be of the order of 10(-6).

Fiber ringdown temperature sensors

A new method of developing fiber temperature sensors using a fiber Bragg grating-loop ringdown scheme is introduced. With this new technique, temperature measurements are converted to measuring time constants. Temperature sensing up to 593°C has been demonstrated using a proof-of-concept device. The sensors stability, repeatability, sensitivity, and dynamic range are also explored.

Measurements of Cavity Ringdown Spectroscopy of Acetone in the Ultraviolet and Near-Infrared Spectral Regions: Potential for Development of a Breath Analyzer

We report a study on the cavity ringdown spectroscopy of acetone in both the ultraviolet (UV) and the near-infrared (NIR) spectral regions to explore the potential for development of a breath analyzer for disease diagnostics. The ringdown spectrum of acetone in the UV (282.4–285.0 nm) region is recorded and the spectrum is in good agreement with those obtained by other spectral techniques reported in the literature. The absorption cross-section of the C–H stretching overtone of acetone in the NIR (1632.7–1672.2 nm) is reported for the first time and the maximum absorption cross-section located at 1666.7 nm is 1.2 × 10−21 cm2. A novel, compact, atmospheric cavity with a cavity length of 10 cm has been constructed and implemented to investigate the technical feasibility of the potential instrument size, optical configuration, and detection sensitivity. The detection limit of such a mini cavity employing ringdown mirrors of reflectivity of 99.85% at 266 nm, where acetone has the strongest absorption, is ∼1.5 ppmv based on the standard 3σ criteria. No real breath gas samples are used in the present study. Discussions on the detection sensitivity and background spectral interferences for the instrument development are presented. This study demonstrates the potential of developing a portable, sensitive breath analyzer for medical applications using the cavity ringdown spectral technique.

A new acetone detection device using cavity ringdown spectroscopy at 266 nm: evaluation of the instrument performance using acetone sample solutions

Acetone in human breath gas has been established as a biomarker for type-1 diabetes (T1D). Non-invasive breath gas analysis for diabetes diagnostics using breath acetone as a biomarker depends on the availability of a portable, fast-response and sensitive acetone detection device. So far such an instrument is not available yet. We report on the first acetone detection device using cavity ringdown spectroscopy and evaluate its performance prior to breath gas testing. Taking advantage of the coincidence of the largest absorption cross-section of acetone in the UV being at 266 nm with the availability of the palm-size 266 nm laser source, we construct a portable ringdown acetone detection device. The high quality single mode laser beam allows us to simplify the optical design for coupling the laser beam into the cavity, which consists of a pair of high reflectivity mirrors (R = 99.87%) separated by 45 cm. The ringdown signal observed by a miniature detector is processed by a laptop computer. The instrument performance on sensitivity, response time and sampling methods is evaluated using acetone diluted in deionized water in the concentration range of 6 drops l?1 to 0.5 drop l?1. The device operating with two different sampling methods is investigated and shows different measurement sensitivities and response times. The minimum detectable concentration of acetone sample solutions is 0.5 drop l?1 or 7.9 ?g l?1, which corresponds to a gas concentration of 0.49 ppmv derived from the measured absorbance (based on 1-?). The typical measuring time in the second sampling method, including the times for the sample introduction, the purge of the gas cell and the data processing, is less than 50 s. Since the average concentration of acetone in healthy human breath gas is approximately 0.79?1.4 ppmv, this instrument has sufficient sensitivity to detect breath acetone with elevated concentrations. Issues in future developments towards an instrument suitable for breath gas testing are discussed.