For a long time, non-communicable diseases have posed one of the greatest challenges to global health and development, with cardiovascular diseases (CVD) standing as the number one killer [1]. The occurrence and development of CVD are progressive. Thus, it is imperative to diagnose and prevent them at an early stage and activate timely warnings for vulnerable individuals to mitigate the risk. Currently, most CVD screenings rely on outpatient testing, with limited continuous monitoring of a patient's status for prevention and control. Over the years, advances in flexible electronic technology have enabled continuous monitoring of physiological status. This includes oxygen sensors using photoplethysmography (PPG) [2], blood pressure sensors based on vibrations [3], or featuring ultrasound [4]. However, these sensors often fall short in terms of precision and richness of characterization necessary for CVD monitoring. Consequently, the challenge of providing real-time prevention, control, and warning for CVD using flexible sensors remains significant.

Influenced by optoacoustic (OA), also known as photoacoustic (PA), multifunctional imaging, our team proposed a flexible optoacoustic blood ‘stethoscope’ (OBS). The OBS is conceived around the OA effect, which delivers light into the blood to induce mechanical vibrations in blood chromophores and subsequently detects the resulting blood signals as acoustic waves. This multilayered device consists of a micro-lens array with pre-drilled holes for light delivery and an alternating piezoelectric sensor array that acts as the acoustic receiver. Designed as a flexible apparatus, the OBS can adhere to the skin, embodying flexible electronic technology. We named our device a blood ‘stethoscope’ because, akin to a traditional stethoscope, it 'listens' to the acoustic waves to ascertain blood properties. Leveraging this pioneering technology, the OBS offers the potential for continuous monitoring of various blood parameters, addressing enduring challenges in the field.






Fig. 1 | Design and working principle of the OBS. a Schematic illustration of the OBS laminated on the surface of the hand. The OBS is based on the optoacoustic effect and can monitor hypoxia, exogenous agent decay, vascular compliance, and endothelial dysfunction. Meanwhile, OBS can map the blood information to a 3D distribution model. b Schematic layout of the OBS: a multi-layered integration of optical (micro-lens), and acoustic (piezo-layer) elements with connection, insulation, electrode, and encapsulation layers. See Methods and Supplementary Figs. 1–2 for the detailed OBS fabrication process. c Photograph of the OBS under bending. d Photograph of the OBS with flexible connecting circuits closely attached to the human wrist. e The cross-distributed acoustic and optical nodes. f, g An exploded view of a single optical (f) and acoustic (g) node.

Distinct from the design principles in recently published flexible ultrasound probes [4-7], our endeavor was to architect a novel design framework that incorporates OA principles. We discerned that the pivotal challenge centered on optimizing the coupling between the optical and acoustic fields. For effective OA imaging, light illumination must be both broad and uniform, while acoustic receivers demand a closely-packed arrangement to guarantee comprehensive signal reception coverage. An intuitive approach to these prerequisites would suggest a fully transparent ultrasound probe that facilitates unhindered light transmission. However, neither the presently available transparent electrodes nor the piezoelectric materials can satisfactorily meet the sensitivity requirements of OA detection. Instead of delving into new materials, our team elected to achieve a structural innovation. We conceived an array probe wherein optical and acoustic elements are organized in a cross pattern, maximizing acoustic field coverage while maintaining light transmission via the pre-drilled holes and layering a focusing microlens array. This design merges the probe's compactness with the robustness of both the optical and acoustic fields.

Addressing the coupling of light and sound also entails considerations for delivering light from the laser to the OBS. Free-space light delivery beyond the imaging window might drastically diminish the OBS's transmission efficiency. Stray light hitting the electrode could potentially generate spike noise or even harm the device. After multiple years of endeavors, our team introduced a discrete fiber bundle light delivery system, significantly enhancing the utilization of light energy, reducing the excitation light fluence needs, and permitting the application of less powerful laser sources.

Emerging from these groundbreaking insights, the flexible OBS was realized. Subsequent to its inception, we embarked on a meticulous validation procedure through a sequence of experimental assessments. Initial tests on mice allowed the OBS to effectively image the oxygen saturation in arteries and veins and monitor the metabolism of exogenous contrast agents in the blood. Further experiments on human subjects evaluated venous elasticity and measured arterial Flow Mediated Dilation (FMD). These persuasive outcomes indicate the prospective application of the OBS for continuous cardiovascular status monitoring, shedding new light on preventative strategies for CVD.

This study entitled " A flexible optoacoustic blood ‘stethoscope’ for noninvasive multiparametric cardiovascular monitoring" has been published in Nature Communications (https://doi.org/10.1038/s41467-023-40181-5).

Reference
[1] Al-Mawali, Adhra. "Non-communicable diseases: shining a light on cardiovascular disease, Oman’s biggest killer." Oman medical journal 30.4 (2015): 227.
[2] Hosanee, Manish, et al. "Cuffless single-site photoplethysmography for blood pressure monitoring." Journal of clinical medicine 9.3 (2020): 723.
[3] Meng, Keyu, et al. "Flexible weaving constructed self‐powered pressure sensor enabling continuous diagnosis of cardiovascular disease and measurement of cuffless blood pressure." Advanced Functional Materials 29.5 (2019): 1806388.
[4] Wang, Chonghe, et al. "Monitoring of the central blood pressure waveform via a conformal ultrasonic device." Nature biomedical engineering 2.9 (2018): 687-695.
[5] Hu, Hongjie, et al. "Stretchable ultrasonic transducer arrays for three-dimensional imaging on complex surfaces." Science advances 4.3 (2018): eaar3979.
[6] Wang, Chonghe, et al. "Continuous monitoring of deep-tissue haemodynamics with stretchable ultrasonic phased arrays." Nature biomedical engineering 5.7 (2021): 749-758.
[7] Lin, Muyang, et al. "A fully integrated wearable ultrasound system to monitor deep tissues in moving subjects." Nature Biotechnology (2023): 1-10.