Time-domain photoacoustic waveform analysis for glucose measurement.

Photoacoustic (PA) effect is the product of light-ultrasound interactions and its time-domain waveform contains rich information. Besides optical absorption, the PA waveform inherently consists of other mechanical and thermal properties of the sample. They also have correlation with the target composition but have not been utilized in conventional PA spectroscopy. In this article, we propose a new concept named time-domain photoacoustic waveform spectroscopy (tPAWS) for chemical component quantification. It employs multiple variables inherently contained in the PA waveform excited by a single wavelength laser to extract informative features. The demonstration of glucose measurement in human blood serum (HBS) shows superior sensitivity and accuracy enhancement, compared to conventional amplitude-based PA measurement and NIR spectroscopy. Thanks to the sensitivity and accuracy of tPAWS, multiple wavelength sources and complex instrumentation used in conventional spectroscopic sensing methods can be avoided. TPAWS, as a novel physics-inspired sensing method, shows great potential for complementing or surpassing the current spectroscopic methods as a new sensing technique for chemical analysis.

Noninvasive Electromagnetic Wave Sensing of Glucose.

Diabetic patients need long-term and frequent glucose monitoring to assist in insulin intake. The current finger-prick devices are painful and costly, which places noninvasive glucose sensors in high demand. In this review paper, we list several advanced electromagnetic (EM)-wave-based technologies for noninvasive glucose measurement, including infrared (IR) spectroscopy, photoacoustic (PA) spectroscopy, Raman spectroscopy, fluorescence, optical coherence tomography (OCT), Terahertz (THz) spectroscopy, and microwave sensing. The development of each method is discussed regarding the fundamental principle, system setup, and experimental results. Despite the promising achievements that have been previously reported, no established product has obtained FDA approval or survived a marketing test. The limitations of, and prospects for, these techniques are presented at the end of this review.

Noninvasive photoacoustic measurement of glucose by data fusion.

We proposed a novel noninvasive method for glucose detection using a photoacoustic (PA) technique utilizing both the peak-to-peak value and peak arrival time delay information. Without increasing apparatus and system complexity, we demonstrated the accuracy enhancement of 29.5% and 33.63% for high (0-7 g dL-1) and low (0-350 mg dL-1) concentration of glucose solution, compared to conventional amplitude-based prediction.

Handheld Photoacoustic Imager for Theranostics in 3D.

A handheld approach to 3D photoacoustic imaging is essential in clinical applications. To this end, we develop a 3D handheld photoacoustic imager for dynamic (temporally and spatially) volumetric visualization. In this 3D imager, the optically transmitting part and the acoustically receiving part are integrated into a single handheld probe with a compact size about 160 mm ×64 mm ×40 mm. Besides, a dedicated imaging reconstruction algorithm for the heterogeneous medium is developed based on the phase-shift migration method in the frequency domain, which deals well with the stratified condition in the designed system. Dynamic 3D imaging supporting flexible handheld operation is demonstrated with needle biopsy and in vitro temperature measurement for photothermal therapy. The development of such a 3D handheld photoacoustic system paves the way for compact and handheld-operating implementations, and its further clinical exploration is promising.

"Guide Star" Assisted Noninvasive Photoacoustic Measurement of Glucose.

A novel "guide star" assisted photoacoustic (GSPA) method for noninvasive glucose measurement has been proposed. Instead of receiving PA signals that are directly generated by tissue, a virtual photodiode is employed to amplify the PA signal difference regarding amplitude and peak arrival time caused by glucose concentration variations in an indirect way. Being different from traditional PA spectroscopy, this method can improve sensitivity and accuracy by optimizing optical path lengths (or tissue thickness). On the other hand, being superior to near-infrared (NIR) spectroscopy, it utilizes both optical absorption and acoustic propagation velocity information confered by PA signals. Theoretical analysis and simulation have been done to illustrate how the concentration change affects the PA waveform. In vitro experiments on aqueous glucose solution were conducted with concentrations varying in human physiological range (50-350 mg/dL). Performance of quartz cuvettes with 1 mm and 2 mm optical path lengths were compared in terms of correlation quality ( R2), degree of agreement (Bland-Altman plot), and clinical accuracy (Clarke's Error Grid analysis) to demonstrate the scalability of sensitivity provided by the indirect method. Longer optical length shows better sensitivity and accuracy in this case. Moreover, detection was also done on human blood serum to further prove the potential of the proposed method for clinical application. Our proposed method provides a solution to enhance sensitivity, facilitating development of portable and low-cost PA sensors with low power laser diodes for noninvasive glucose monitoring and other applications.