摘要： 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 offered 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 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.