Electrochemical Lateral Flow Immunoassay with Built-In Electrodes for Ultrasensitive and Wireless Detection of Inflammatory Biomarkers.

Paper-based lateral flow immunoassays (LFIAs) are cost-effective, portable, and simple methods for detection of diverse analytes, which however only provide qualitative or semiquantitative results and lack sufficient sensitivity. A combination of LFIA and electrochemical detection, namely, electrochemical lateral flow immunoassay (eLFIA), enables quantitative detection of analytes with high sensitivity, but the integration of external electrodes makes the system relatively expensive and unstable. Herein, the working, counter, and reference electrodes were prepared directly on the nitrocellulose membrane using screen printing, which remarkably simplified the structure of eLFIA and decreased the cost. Moreover, a horseradish peroxidase (HRP)-based electrochemical signal amplification strategy was used for further increasing the analytical sensitivity. HRP captured on the working electrode can catalyze the oxidation of tetramethylbenzidine (TMB) to form the TMB-TMBox precipitate on the electrode surface, which as an electrochemically active product can output an amplified current for quantification. We demonstrated that the eLFIA could detect low-abundant inflammatory biomarkers in human plasma samples with limits of detection of 0.17 and 0.54 pg mL-1 for interleukin-6 and C-reactive protein, respectively. Finally, a fully portable system was fabricated by integrating eLFIA with a flexible and wireless electrochemical workstation, realizing the point-of-care detection of interleukin-6.

In Vivo Electrochemical Measurement of Glucose Variation in the Brain of Early Diabetic Mice.

Diabetes is a chronic disease caused by a decrease in insulin level or insulin resistance. Diabetes also has detrimental effects on the brain, which can lead to the injury of the blood-brain barrier and influence the glucose transport. In this study, we use in vivo electrochemical measurement to explore the glucose variation in the brain of early diabetic mice. The glucose level in mice brain is measured using a carbon fiber microelectrode modified with the osmium-derivatized polymer and glucose oxidase. The electrode shows an excellent electrochemical performance, antibiofouling ability, and high stability, which can work stably in the mice brain for 2 h. By monitoring the glucose level in the brain of normal and diabetic mice after injection of concentrated glucose solution into the abdominal cavity, it is found that the variation of cerebral glucose decreases by ∼2 fold for diabetic mice. It is proposed that diabetes can downregulate the activity of glucose transporter in the brain and finally inhibit the brain glucose uptake.

An integrated microfluidic electrochemiluminescence device for point-of-care testing of acute myocardial infarction.

Heart-type fatty acid binding protein (H-FABP) is an early biomarker for acute myocardial infarction. The concentration of H-FABP in circulation sharply increases during myocardial injury. Therefore, fast and accurate detection of H-FABP is of vital significance. In this study, we developed an electrochemiluminescence device integrated with microfluidic chip (designed as m-ECL device) for on-site detection of H-FABP. The m-ECL device is consisted of a microfluidic chip that enable easy liquid handling as well as an integrated electronic system for voltage supply and photon detection. A sandwich-type ECL immunoassay strategy was employed for H-FABP detection by using Ru (bpy)32+ loaded mesoporous silica nanoparticles as ECL probes. This device can directly detect H-FABP in human serum without any pre-treatment, with a wide linear range of 1-100 ng/mL and a low limit of detection of 0.72 ng/mL. The clinical usability of this device was evaluated using clinical serum samples from patients. The results obtained from m-ECL device are well matched with those obtained from ELISA assays. We believe this m-ECL device has extensive application prospects for point-of-care testing of acute myocardial infarction.

Spike-based adenovirus vectored COVID-19 vaccine does not aggravate heart damage after ischemic injury in mice.

An unprecedented number of COVID-19 vaccination campaign are under way worldwide. The spike protein of SARS-CoV-2, which majorly binds to the host receptor angiotensin converting enzyme 2 (ACE2) for cell entry, is used by most of the vaccine as antigen. ACE2 is highly expressed in the heart and has been reported to be protective in multiple organs. Interaction of spike with ACE2 is known to reduce ACE2 expression and affect ACE2-mediated signal transduction. However, whether a spike-encoding vaccine will aggravate myocardial damage after a heart attack via affecting ACE2 remains unclear. Here, we demonstrate that cardiac ACE2 is up-regulated and protective after myocardial ischemia/reperfusion (I/R). Infecting human cardiac cells or engineered heart tissues with a spike-based adenovirus type-5 vectored COVID-19 vaccine (AdSpike) does not affect their survival and function, whether subjected to hypoxia-reoxygenation injury or not. Furthermore, AdSpike vaccination does not aggravate heart damage in wild-type or humanized ACE2 mice after I/R injury, even at a dose that is ten-fold higher as used in human. This study represents the first systematic evaluation of the safety of a leading COVID-19 vaccine under a disease context and may provide important information to ensure maximal protection from COVID-19 in patients with or at risk of heart diseases.

Real time detection of 3-nitrotyrosine using smartphone-based electrochemiluminescence.

As an oxidase stress biomarker, 3-nitrotyrosine is closely associated with many cardiovascular diseases. Thus, early diagnosis and real time detection of 3-nitrotyrosine at bedside are highly important. Herein, we developed a handheld electrochemiluminescence (ECL) analysis device, which integrates printed circuit board (PCB) for electrical stimulation and smartphone for optical signals readout. Fast and accurate determination of 3-nitrotyrosine was achieved with Antibody/Ru(dcpy)32+@AuNPs/MoS2 modified Au electrode (Ab/Ru@AuNPs/MoS2) for ECL analysis. The linear range of 3-nitrotyrosine detection was from 10-8 mol/L to 10-6 mol/L with a detection limit of 8.4 × 10-9 mol/L. In addition, an Android application was developed to realize real time analysis of ECL emissions and results readout for detection. To confirm the usage of the device, spiked serum with different concentrations was tested and the results indicated the practical reliability and stability of this device. The operating procedure for ECL analysis in this device is extremely easy and electrical stimulation was adjustable from 0 V to 5 V for general ECL systems. Thus, we believe this handheld device for ECL analysis has extensive prospects for application in Point-of-care testing and health caring.

Implantable platinum nanotree microelectrode with a battery-free electrochemical patch for peritoneal carcinomatosis monitoring.

As a severe stage of cancers, peritoneal carcinomatosis should be frequently monitored by means of ascites analysis. Nevertheless, the analysis process is traumatic and time-consuming in clinical practice. In this study, an implantable platinum nanotree microelectrode with a wireless, battery-free and flexible electrochemical patch was developed for in vivo and real-time peritoneal glucose detection to monitor peritoneal carcinomatosis. As the core of implantable microelectrode, platinum trees were synthesized by one-step electrodeposition method and highly sensitive to glucose detection. The platinum nanotree microelectrode was implantable in peritoneal cavity in minimally invasive way. A flexible circuit patch could execute electrochemical test and realize wireless power harvesting and data interaction with a near field communication (NFC)-enabled smartphone. The whole system could detect glucose dynamics in vivo in rat peritoneal cavity. Furthermore, the accuracy of this system was validated in ascites of patients. In this way, the system could offer hassle-free, rapid and minimally invasive opportunities toward peritoneal carcinomatosis monitoring.

Wireless, battery-free and wearable device for electrically controlled drug delivery: sodium salicylate released from bilayer polypyrrole by near-field communication on smartphone.

Compared with traditional drug delivery methods, transdermal drug delivery has many advantages in avoiding the side effects in gastrointestinal tract, reducing the fluctuations in drug concentration, and improving patients' compliance. Among them, electrically controlled drug delivery is a promising solution. This work presents a wireless, battery-free and wearable device with electrically controlled drug delivery capability. The electronic component of the device is a flexible circuit board with a temperature sensor and a near-field communication module. With the help of smartphone, the device could wirelessly obtain energy and implement data transmission. The drug delivery component is a paper-based electrode modified with polypyrrole, in which non-steroidal anti-inflammatory drug sodium salicylate was encapsulated. The applied potential for electrically controlled drug delivery was more negative than -0.6 V. The drug release dose and release rates could be controlled by applying potentials with different amplitudes and durations through this device. It provided a minimalized wearable transdermal drug delivery platform for monitoring diseases such as gout. This wearable device shows promising potential in develop closed-loop drug delivery and monitoring systems for the treatment of various diseases.

Salivary Cortisol Determination on Smartphone-Based Differential Pulse Voltammetry System.

Cortisol is commonly used as a significant biomarker of psychological or physical stress. With the accelerated pace of life, non-invasive cortisol detection at the point of care (POC) is in high demand for personal health monitoring. In this paper, an ultrasensitive immunosensor using gold nanoparticles/molybdenum disulfide/gold nanoparticles (AuNPs/MoS2/AuNPs) as transducer was explored for non-invasive salivary cortisol monitoring at POC with the miniaturized differential pulse voltammetry (DPV) system based on a smartphone. Covalent binding of cortisol antibody (CORT-Ab) onto the AuNPs/MoS2/AuNPs transducer was achieved through the self-assembled monolayer of specially designed polyethylene glycol (PEG, SH-PEG-COOH). Non-specific binding was avoided by passivating the surface with ethanolamine. The miniaturized portable DPV system was utilized for human salivary cortisol detection. A series current response of different cortisol concentrations decreased and exhibited a linear range of 0.5-200 nM, the detection limit of 0.11 nM, and high sensitivity of 30 µA M-1 with a regression coefficient of 0.9947. Cortisol was also distinguished successfully from the other substances in saliva. The recovery ratio of spiked human salivary cortisol and the variation of salivary cortisol level during one day indicated the practicability of the immunosensor based on the portable system. The results demonstrated the excellent performance of the smartphone-based immunosensor system and its great potential application for non-invasive human salivary cortisol detection at POC.