Mid-Infrared Photoacoustic Detection of Glucose in Human Skin: Towards Non-Invasive Diagnostics.

Diabetes mellitus is a widespread metabolic disease without cure. Great efforts are being made to develop a non-invasive monitoring of the blood glucose level. Various attempts have been made, including a number of non-optical approaches as well as optical techniques involving visible, near- and mid-infrared light. However, no true breakthrough has been achieved so far, i.e., there is no fully non-invasive monitoring device available. Here we present a new study based on mid-infrared spectroscopy and photoacoustic detection. We employ two setups, one with a fiber-coupled photoacoustic (PA) cell and a tunable quantum cascade laser (QCL), and a second setup with two QCLs at different wavelengths combined with PA detection. In both cases, the PA cells are in direct skin contact. The performance is tested with an oral glucose tolerance test. While the first setup often gives reasonable qualitative agreement with ordinary invasive blood glucose measurements, the dual-wavelength approach yields a considerably improved stability and an uncertainty of only ±30 mg/dL of the blood glucose concentration level at a confidence level of 90%. This result is achieved without advanced data treatment such as principal component analysis involving extended wavelength ranges.

Quantitative chemical analysis of surgical smoke generated during laparoscopic surgery with a vessel-sealing device.

BACKGROUND: Exposure to surgical smoke in the operation room has been a long-standing concern. Smoke generated by the interaction between lasers or electrocautery devices with biological tissue contains several toxic and carcinogenic substances, but only a few studies so far have provided quantitative data necessary for risk assessment. METHODS: With laser and Fourier-transform infrared spectroscopy, we investigated the chemical composition of smoke produced with a vessel-sealing device in an anoxic environment during laparoscopic surgery. RESULTS: Harmless concentrations of methane (<34 ppm), ethane (<2 ppm), and ethylene (<10 ppm) were detected. Traces of carbon monoxide (<3.2 ppm) and of the anesthetic sevoflurane (<450 ppm) were also found. CONCLUSIONS. Gas leaking or gas being released from the pneumoperitoneum could therefore increase pollution by waste anesthetic gas in the operating room. Most toxic compounds found in earlier studies remained undetected. Adverse health effects for operating room personnel due to some of those substances (e.g., toluene, styrene, xylene) can be excluded, assuming no significant losses or changes in the chemical composition of the samples occurred between our sampling and measurements.

Mid-infrared fiber-coupled photoacoustic sensor for biomedical applications.

Biomedical devices employed in therapy, diagnostics and for self-monitoring often require a high degree of flexibility and compactness. Many near infrared (NIR) optical fiber-coupled systems meet these requirements and are employed on a daily basis. However, mid-infrared (MIR) fibers-based systems have not yet found their way to routine application in medicine. In this work we present the implementation of the first MIR fiber-coupled photoacoustic sensor for the investigation of condensed samples in the MIR fingerprint region. The light of an external-cavity quantum-cascade laser (1010-1095 cm(-1)) is delivered by a silver halide fiber, which is attached to the PA cell. The PA chamber is conically shaped to perfectly match the beam escaping the fiber and to minimize the cell volume. This results in a compact and handy sensor for investigations of biological samples and the monitoring of constituents both in vitro and in vivo. The performance of the fiber-coupled PA sensor is demonstrated by sensing glucose in aqueous solutions. These measurements yield a detection limit of 57 mg/dL (SNR = 1). Furthermore, the fiber-coupled sensor has been applied to record human skin spectra at different body sites to illustrate its flexibility.

Vapor-phase infrared laser spectroscopy: from gas sensing to forensic urinalysis.

Numerous gas-sensing devices are based on infrared laser spectroscopy. In this paper, the technique is further developed and, for the first time, applied to forensic urinalysis. For this purpose, a difference frequency generation laser was coupled to an in-house-built, high-temperature multipass cell (HTMC). The continuous tuning range of the laser was extended to 329 cm(-1) in the fingerprint C-H stretching region between 3 and 4 microm. The HTMC is a long-path absorption cell designed to withstand organic samples in the vapor phase (Bartlome, R.; Baer, M.; Sigrist, M. W. Rev. Sci. Instrum. 2007, 78, 013110). Quantitative measurements were taken on pure ephedrine and pseudoephedrine vapors. Despite featuring similarities, the vapor-phase infrared spectra of these diastereoisomers are clearly distinguishable with respect to a vibrational band centered at 2970.5 and 2980.1 cm(-1), respectively. Ephedrine-positive and pseudoephedrine-positive urine samples were prepared by means of liquid-liquid extraction and directly evaporated in the HTMC without any preliminary chromatographic separation. When 10 or 20 mL of ephedrine-positive human urine is prepared, the detection limit of ephedrine, prohibited in sports as of 10 microg/mL, is 50 or 25 microg/mL, respectively. The laser spectrometer has room for much improvement; its potential is discussed with respect to doping agents detection.

Glucose sensing in human epidermis using mid-infrared photoacoustic detection.

No reliable non-invasive glucose monitoring devices are currently available. We implemented a mid-infrared (MIR) photoacoustic (PA) setup to track glucose in vitro in deep epidermal layers, which represents a significant step towards non-invasive in vivo glucose measurements using MIR light. An external-cavity quantum-cascade laser (1010-1095 cm(-1)) and a PA cell of only 78 mm(3) volume were employed to monitor glucose in epidermal skin. Skin samples are characterized by a high water content. Such samples investigated with an open-ended PA cell lead to varying conditions in the PA chamber (i.e., change of light absorption or relative humidity) and cause unstable signals. To circumvent variations in relative humidity and possible water condensation, the PA chamber was constantly ventilated by a 10 sccm N(2) flow. By bringing the epidermal skin samples in contact with aqueous glucose solutions with different concentrations (i.e., 0.1-10 g/dl), the glucose concentration in the skin sample was varied through passive diffusion. The achieved detection limit for glucose in epidermal skin is 100 mg/dl (SNR=1). Although this lies within the human physiological range (30-500 mg/dl) further improvements are necessary to non-invasively monitor glucose levels of diabetes patients. Furthermore spectra of epidermal tissue with and without glucose content have been recorded with the tunable quantum-cascade laser, indicating that epidermal constituents do not impair glucose detection.

Laser fibre deterioration and loss of power output during photo-selective 80-w potassium-titanyl-phosphate laser vaporisation of the prostate.

BACKGROUND: The potassium-titanyl-phosphate (KTP) laser technique for photo-selective vaporisation of the prostate (PVP) has been regularly improved over the last decade. Nonetheless, decreasing efficiency of tissue vaporisation during the course of the operation and macroscopic alterations of the laser fibre's tip are regularly observed and seem to affect the outcome of this procedure. OBJECTIVE: To investigate the course of power output and to determine the type and extent of fibre deterioration during PVP. DESIGN, SETTING, AND PARTICIPANTS: Forty laser fibres were investigated during PVP in 35 consecutive patients with prostatic bladder outflow obstruction between January 2007 and August 2007 in a university hospital. INTERVENTION: All patients underwent PVP performed by three different surgeons using the 80-W KTP laser. MEASUREMENTS: Power output was measured at the beginning and regularly throughout PVP and throughout in vitro vaporisation without fibre-tissue contact. Microscopic documentation of the fibre tip was performed after the procedure. RESULTS AND LIMITATIONS: Carbonisation and melting of the fibre tip was regularly visible and appeared to be more pronounced as more energy was applied. Additionally, 90% of the fibres showed a significant decrease of power output during PVP, resulting in an end-of-lifespan (ie, 275-kilojoule) median power output of 20% of the initial value. Final median power output after in vitro vaporisation was 83% of the starting value. The extent of the structural and functional changes might only be valid for the operative technique performed in this investigation. CONCLUSIONS: Fibre deterioration caused significant reduction of power output during PVP. This finding is an explanation for the often observed decreasing efficiency of tissue ablation and may also be responsible for some of the typical drawbacks and complications of PVP. Hence, improvements in fibre quality are necessary to advance the efficiency of this technique.

Spectroscopic investigation of methylated amines by a cavity-ringdown-based spectrometer.

High-resolution absorption spectra of gas-phase monomethylamine (MMA, CH(3)NH(2)) and dimethylamine [DMA, (CH(3))(2)NH] in the region of the first overtone of the NH stretch vibration are reported. Measurements were performed with a near-infrared laser spectrometer based on the cavity-ringdown (CRD) detection technique. The minimum detectable absorption coefficient for the CRD detection setup is alpha(min)=1.55 x 10(-8) cm(-1) (for SNR = 1). This corresponds to detection limits of 350 parts in 10(9) (ppb) for MMA and 1.6 parts in 10(6) (ppm) for DMA in synthetic gas mixtures under interference-free conditions, or 10 ppm and 60 ppm for MMA and DMA, respectively, in the case of gas mixtures such as exhaled human breath containing H(2)O, CO(2), and other absorbing gases in this range.