The COVID-19 pandemic is an ongoing global challenge for public health systems. Ultrasensitive and early identification of infection is critical to prevent widespread COVID-19 infection by presymptomatic and asymptomatic individuals, especially in the community and in-home settings. We demonstrate a multiplexed, portable, wireless electrochemical platform for ultra-rapid detection of COVID-19: the SARS-CoV-2 RapidPlex. It detects viral antigen nucleocapsid protein, IgM and IgG antibodies, as well as the inflammatory biomarker C-reactive protein, based on our mass-producible laser-engraved graphene electrodes. We demonstrate ultrasensitive, highly selective, and rapid electrochemical detection in the physiologically relevant ranges. We successfully evaluated the applicability of our SARS-CoV-2 RapidPlex platform with COVID-19 positive and negative blood and saliva samples. Based on this pilot study, our multiplexed immunosensor platform may allow for high frequency at-home testing for COVID-19 telemedicine diagnosis and monitoring.
The management of the COVID-19 pandemic has relied on cautious contact tracing, quarantine, and sterilization protocols while we await a vaccine to be made widely available. Telemedicine or mobile health (mHealth) is well-positioned during this time to reduce potential disease spread and prevent overloading of the healthcare system through at-home COVID-19 screening, diagnosis, and monitoring. With the rise of mass-fabricated electronics for wearable and portable sensors, emerging telemedicine tools have been developed to address shortcomings in COVID-19 diagnostics, monitoring, and management. In this Perspective, we summarize current implementations of mHealth sensors for COVID-19, highlight recent technological advances, and provide an overview on how these tools may be utilized to better control the COVID-19 pandemic.
Wearable sensors hold great potential in empowering personalized health monitoring, predictive analytics, and timely intervention toward personalized healthcare. Advances in flexible electronics, materials science, and electrochemistry have spurred the development of wearable sweat sensors that enable the continuous and noninvasive screening of analytes indicative of health status. Existing major challenges in wearable sensors include: improving the sweat extraction and sweat sensing capabilities, improving the form factor of the wearable device for minimal discomfort and reliable measurements when worn, and understanding the clinical value of sweat analytes toward biomarker discovery. This review provides a comprehensive review of wearable sweat sensors and outlines stateof-the-art technologies and research that strive to bridge these gaps. The physiology of sweat, materials, biosensing mechanisms and advances, and approaches for sweat induction and sampling are introduced. Additionally, design considerations for the system-level development of wearable sweat sensing devices, spanning from strategies for prolonged sweat extraction to efficient powering of wearables, are discussed. Furthermore, the applications, data analytics, commercialization efforts, challenges, and prospects of wearable sweat sensors for precision medicine are discussed.
Nanorobotic manipulation to access subcellular organelles remains unmet due to the challenge in achieving intracellular controlled propulsion. Intracellular organelles, such as mitochondria, are an emerging therapeutic target with selective targeting and curative efficacy. We report an autonomous nanorobot capable of active mitochondria-targeted drug delivery, prepared by facilely encapsulating mitochondriotropic doxorubicin-triphenylphosphonium (DOX-TPP) inside zeolitic imidazolate framework-67 (ZIF-67) nanoparticles. The catalytic ZIF-67 body can decompose bioavailable hydrogen peroxide overexpressed inside tumor cells to generate effective intracellular mitochondriotropic movement in the presence of TPP cation. This nanorobot-enhanced targeted drug delivery induces mitochondria-mediated apoptosis and mitochondrial dysregulation to improve the in vitro anticancer effect and suppression of cancer cell metastasis, further verified by in vivo evaluations in the subcutaneous tumor model and orthotopic breast tumor model. This nanorobot unlocks a fresh field of nanorobot operation with intracellular organelle access, thereby introducing the next generation of robotic medical devices with organelle-level resolution for precision therapy.
Leptospirosis is a neglected zoonotic disease with worldwide endemicity and continues to be a significant public health burden on resource-limited populations. Previously, we produced three highly purified recombinant antigens (rLipL32, rLipL41, and rLigA-Rep) and evaluated their performance of detecting -specific antibodies in enzyme-linked immunosorbent assay (ELISA) as compared with the microscopic agglutination test (MAT). The overall sensitivity of this assay approached 90%. Recently, another recombinant antigen (rLigB-Rep) was prepared. We tested each individual antigen and a 1:1:1:1 mixture of these four antigens for the detection of-specific antibodies in ELISA. The performance of these recombinant antigens was evaluated with a much larger febrile patient panel (337 MAT-confirmed positive sera and 92 MAT-negative sera from febrile patients). Combining the detection results of immunoglobulin M and immunoglobulin G from these four individual antigens, the overall sensitivity was close to 90% but the specificity was only 66%, based on the MAT reference method. The overall sensitivity and specificity of the four-antigen mixture were 82% and 86%, respectively. The mixture of four antigens also exhibited a broader reactivity with MAT-positive samples of 18 serovars from six major pathogenic species. Given the limitations of MAT, the data were further analyzed by Bayesian latent class model, showing that ELISA using a 1:1:1:1 mixture still maintained high sensitivity (79%) and specificity (88%) as compared with the sensitivity (90%) and specificity (83%) of MAT. Therefore, ELISA using a mixture of these four antigens could be a very useful test for seroprevalence studies.
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