RESUMO
The rapid advancements in nucleic acid-based electrochemical sensors for implantable and wearable applications have marked a significant leap forward in the domain of personal healthcare over the last decade. This technology promises to revolutionize personalized healthcare by facilitating the early diagnosis of diseases, monitoring of disease progression, and tailoring of individual treatment plans. This review navigates through the latest developments in this field, focusing on the strategies for nucleic acid sensing that enable real-time and continuous biomarker analysis directly in various biofluids, such as blood, interstitial fluid, sweat, and saliva. The review delves into various nucleic acid sensing strategies, emphasizing the innovative designs of biorecognition elements and signal transduction mechanisms that enable implantable and wearable applications. Special perspective is given to enhance nucleic acid-based sensor selectivity and sensitivity, which are crucial for the accurate detection of low-level biomarkers. The integration of such sensors into implantable and wearable platforms, including microneedle arrays and flexible electronic systems, actualizes their use in on-body devices for health monitoring. We also tackle the technical challenges encountered in the development of these sensors, such as ensuring long-term stability, managing the complexity of biofluid dynamics, and fulfilling the need for real-time, continuous, and reagentless detection. In conclusion, the review highlights the importance of these sensors in the future of medical engineering, offering insights into design considerations and future research directions to overcome existing limitations and fully realize the potential of nucleic acid-based electrochemical sensors for healthcare applications.
Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Ácidos Nucleicos , Dispositivos Eletrônicos Vestíveis , Humanos , Ácidos Nucleicos/análise , Biomarcadores/análise , Biomarcadores/sangueRESUMO
Many systems have been designed for the detection of SARS-CoV-2, which is the virus that causes COVID-19. SARS-CoV-2 is readily transmitted, resulting in the rapid spread of disease in human populations. Frequent testing at the point of care (POC) is a key aspect for controlling outbreaks caused by SARS-CoV-2 and other emerging pathogens, as the early identification of infected individuals can then be followed by appropriate measures of isolation or treatment, maximizing the chances of recovery and preventing infectious spread. Diagnostic tools used for high-frequency testing should be inexpensive, provide a rapid diagnostic response without sophisticated equipment, and be amenable to manufacturing on a large scale. The application of these devices should enable large-scale data collection, help control viral transmission, and prevent disease propagation. Here we review functional nanomaterial-based optical and electrochemical biosensors for accessible POC testing for COVID-19. These biosensors incorporate nanomaterials coupled with paper-based analytical devices and other inexpensive substrates, traditional lateral flow technology (antigen and antibody immunoassays), and innovative biosensing methods. We critically discuss the advantages and disadvantages of nanobiosensor-based approaches compared to widely used technologies such as PCR, ELISA, and LAMP. Moreover, we delineate the main technological, (bio)chemical, translational, and regulatory challenges associated with developing functional and reliable biosensors, which have prevented their translation into the clinic. Finally, we highlight how nanobiosensors, given their unique advantages over existing diagnostic tests, may help in future pandemics.
Assuntos
Técnicas Biossensoriais , COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Teste para COVID-19 , Pandemias , Técnicas Biossensoriais/métodos , TecnologiaRESUMO
Personalized monitoring of female hormones (for example, oestradiol) is of great interest in fertility and women's health. However, existing approaches usually require invasive blood draws and/or bulky analytical laboratory equipment, making them hard to implement at home. Here we report a skin-interfaced wearable aptamer nanobiosensor based on target-induced strand displacement for automatic and non-invasive monitoring of oestradiol via in situ sweat analysis. The reagentless, amplification-free and 'signal-on' detection approach coupled with a gold nanoparticle-MXene-based detection electrode offers extraordinary sensitivity with an ultra-low limit of detection of 0.14 pM. This fully integrated system is capable of autonomous sweat induction at rest via iontophoresis, precise microfluidic sweat sampling controlled via capillary bursting valves, real-time oestradiol analysis and calibration with simultaneously collected multivariate information (that is, temperature, pH and ionic strength), as well as signal processing and wireless communication with a user interface (for example, smartphone). We validated the technology in human participants. Our data indicate a cyclical fluctuation in sweat oestradiol during menstrual cycles, and a high correlation between sweat and blood oestradiol was identified. Our study opens up the potential for wearable sensors for non-invasive, personalized reproductive hormone monitoring.
Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Dispositivos Eletrônicos Vestíveis , Humanos , Feminino , Ouro , Pele , EstradiolRESUMO
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.
Assuntos
Estruturas Metalorgânicas , Nanopartículas , Neoplasias , Humanos , Estruturas Metalorgânicas/farmacologia , Portadores de Fármacos/farmacologia , Sistemas de Liberação de Medicamentos , Doxorrubicina/farmacologia , Neoplasias/tratamento farmacológico , Nanopartículas/ultraestrutura , MitocôndriasRESUMO
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 state-of-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.
Assuntos
Técnicas Biossensoriais , Pele , Dispositivos Eletrônicos Vestíveis , Eletrônica , Monitorização Fisiológica , Medicina de Precisão , SuorRESUMO
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.
Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , COVID-19/terapia , Gerenciamento Clínico , SARS-CoV-2/genética , Telemedicina/métodos , Antígenos Virais/análise , Técnicas Biossensoriais/instrumentação , COVID-19/patologia , COVID-19/virologia , Teste para COVID-19/instrumentação , Busca de Comunicante/instrumentação , Humanos , Aplicativos Móveis/provisão & distribuição , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Nanotecnologia/instrumentação , Nanotecnologia/métodos , Distanciamento Físico , Sistemas Automatizados de Assistência Junto ao Leito/organização & administração , Testes Imediatos/organização & administração , Quarentena/organização & administração , SARS-CoV-2/imunologia , Telemedicina/instrumentaçãoRESUMO
The COVID-19 pandemic is an ongoing global challenge for public health systems. Ultrasensitive and early identification of infection is critical in preventing 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 COVID-19-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.
RESUMO
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 Leptospira-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 Leptospira-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 Leptospira 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.