Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.

Technology Roadmap for Flexible Sensors.

Osteoarthritis affects millions of people worldwide but current treatments using analgesics or anti-inflammatory drugs only alleviate symptoms of this disease. Here, we present an injectable, biodegradable piezoelectric hydrogel, made of short electrospun poly-L-lactic acid nanofibers embedded inside a collagen matrix, which can be injected into the joints and self-produce localized electrical cues under ultrasound activation to drive cartilage healing. In vitro, data shows that the piezoelectric hydrogel with ultrasound can enhance cell migration and induce stem cells to secrete TGF-β1, which promotes chondrogenesis. In vivo, the rabbits with osteochondral critical-size defects receiving the ultrasound-activated piezoelectric hydrogel show increased subchondral bone formation, improved hyaline-cartilage structure, and good mechanical properties, close to healthy native cartilage. This piezoelectric hydrogel is not only useful for cartilage healing but also potentially applicable to other tissue regeneration, offering a significant impact on the field of regenerative tissue engineering. 

Injectable and biodegradable piezoelectric hydrogel for osteoarthritis treatment

Moisture detection plays a crucial role in physiological monitoring and wearable electronics. Nevertheless, most of the humidity sensors were restricted by the power supply, hindering their applicability in internet of things and mobile healthcare. Herein, we reported a hierarchical piezoelectric composite film for active humidity detection and wearable biomonitoring. The as-electrospun piezoelectric transducing textile consists of samarium-modified lead magnesium niobate lead titanate piezoceramic fillers and polyvinylidene fluoride matrix, while the spin coated polyimide film serves as the humidity sensitive layer. By tuning the thickness ratio between transducing layer and the humidity sensing layer as well as the porosity of the electrode, an optimal moisture-sensing performance was accomplished with a high response of ∼500% and rapid response/recovery time of 23 s/31 s. Furthermore, a theoretical modeling of active humidity sensing mechanism was established by combining thermodynamic derivation and finite element calculation.

Hierarchical piezoelectric composite film for self-powered moisture detection and wearable biomonitoring

Fabrication of novel rational Ti-Sn doped Cu-ferrite nanoparticles for robust photocatalysis reaction, magnetic resonance imaging, and chemo-magneto-photo-thermal therapy

Modern healthcare is transforming from hospital-centric to individual-centric systems. Emerging implantable and wearable medical (IWM) devices are integral parts of enabling affordable and accessible healthcare. Early disease diagnosis and preventive measures are possible by continuously monitoring clinically significant physiological parameters. However, most IWM devices are battery-operated, requiring replacement, which interrupts the proper functioning of these devices. For the continuous operation of medical devices for an extended period of time, supplying uninterrupted energy is crucial. A sustainable and health-compatible energy supply will ensure the high-performance real-time functioning of IWM devices and prolong their lifetime. Therefore, harvesting energy from the human body and ambient environment is necessary for enduring precision healthcare and maximizing user comfort. Energy harvesters convert energy from various sources into an equivalent electrical form. This paper presents a state-of-the-art comprehensive review of energy harvesting techniques focusing on medical applications. Various energy harvesting approaches, working principles, and the current state are discussed. In addition, the advantages and limitations of different methods are analyzed and existing challenges and prospects for improvement are outlined. This paper will help with understanding the energy harvesting technologies for the development of high-efficiency, reliable, robust, and battery-free portable medical devices.

/pdf/energy-harvesting-in-implantable-and-wearable-medical-h2e5k5xx.pdf

Energy Harvesting in Implantable and Wearable Medical Devices for Enduring Precision Healthcare

Supplying wireless power is a challenging technical problem of great importance for implantable biomedical devices. Here, we introduce a novel implantable piezoelectric ultrasound energy–harvesting device based on Sm-doped Pb(Mg1/3Nb2/3)O3-PbTiO3 (Sm-PMN-PT) single crystal. The output power density of this device can reach up to 1.1 W/cm2 in vitro, which is 18 times higher than the previous record (60 mW/cm2). After being implanted in the rat brain, under 1-MHz ultrasound with a safe intensity of 212 mW/cm2, the as-developed device can produce an instantaneous effective output power of 280 μW, which can immediately activate the periaqueductal gray brain area. The rat electrophysiological experiments under anesthesia and behavioral experiments demonstrate that our wireless-powered device is well qualified for deep brain stimulation and analgesia applications. These encouraging results provide new insights into the development of implantable devices in the future.

Piezoelectric ultrasound energy–harvesting device for deep brain stimulation and analgesia applications

Determining the amount of a drug transferred into breast milk is critical for benefit-risk analysis of breastfeeding when a lactating mother takes medications. In this study, we developed a human mammary epithelial cell (MEC)-based permeability assay to assess drug permeability across the mammary epithelium. Human MEC cell MCF10F formed tight junctions when cultured on Transwells with culture medium containing insulin, hydrocortisone and epidermal growth factor (EGF). Formation of integral cell barrier and morphology of the cells were confirmed by assessing trans-epithelial electrical resistance (TEER), flux of fluorescent tracers and imaging with transmission electron microscopy (TEM). MCF10F cells showed consistent P-glycoprotein (P-gp) transporter expression when culturing on Transwell inserts versus on petri dish. A few P-gp transporter drug substrates were used to estimate the permeability from this assay. Human plasma and breast milk were used as incubation medium in basolateral and apical chambers respectively to mimic physiological conditions. The predicted milk to plasma (M/P) ratios were reasonably good. The current effort to develop the MEC-based permeability assay to facilitate M/P ratio prediction showed promising results. This assay may have a potential to be developed as a useful in vitro technique for determining the transfer of small-molecule therapeutic drugs into breast milk. 

https://doi.org/10.1016/j.ijpx.2022.100122

An in vitro human mammary epithelial cell permeability assay to assess drug secretion into breast milk

The solidification microstructure and the microhardness of Al-11Mg-4.5Zn alloy under high pressure were researched by optical microscope, scanning electron microscope (SEM), X-ray diffraction(XRD) and microhardness tester. The results revealed that high pressure solidification refined the dendrite structure, and made the primary dendrite arms grow long. The alloy all consisted of α-Al phase and Mg32(Al, Zn)49 phase whether under normal pressure or high pressure solidification conditions. However, the morphology of the Mg32(Al, Zn)49 phases changed from fork-like of normal pressure to the graininess of high pressure, the size of them reduced, and that of the amount decreased. Furthermore, the solid solubility of Mg and Zn in α-Al phase increased comparing with those of normal pressure, and they were the largest at 4GPa high pressure, reaching 11.37% and 4.15%, respectively. The microhardness of Al-Mg-Zn alloy had an increment with the pressure increasing.

Research on High Pressure Solidification Microstructure and the Microhardness of Al-Mg-Zn Alloy

Ribonucleotide reductase M2 subunit silencing suppresses tumorigenesis in pancreatic cancer via inactivation of PI3K/AKT/mTOR pathway.

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Piezoelectric ultrasound energy–harvesting device for deep brain stimulation and analgesia applications

An in vitro human mammary epithelial cell permeability assay to assess drug secretion into breast milk

Research on High Pressure Solidification Microstructure and the Microhardness of Al-Mg-Zn Alloy

Ribonucleotide reductase M2 subunit silencing suppresses tumorigenesis in pancreatic cancer via inactivation of PI3K/AKT/mTOR pathway.