An Edible Rechargeable Battery.

Edible electronics is a growing field that aims to produce digestible devices using only food ingredients and additives, thus addressing many of the shortcomings of ingestible electronic devices. Edible electronic devices will have major implications for gastrointestinal tract monitoring, therapeutics, as well as rapid food quality monitoring. Recent research has demonstrated the feasibility of edible circuits and sensors, but to realize fully edible electronic devices edible power sources are required, of which there have been very few examples. Drawing inspiration from living organisms, which use redox cofactors to power biochemical machines, a rechargeable edible battery formed from materials eaten in everyday life is developed. The battery is realized by immobilizing riboflavin and quercetin, common food ingredients and dietary supplements, on activated carbon, a widespread food additive. Riboflavin is used as the anode, while quercetin is used as the cathode. By encapsulating the electrodes in beeswax, a fully edible battery is fabricated capable of supplying power to small electronic devices. The proof-of-concept battery cell operated at 0.65 V, sustaining a current of 48 µA for 12 min. The presented proof-of-concept will open the doors to new edible electronic applications, enabling safer and easier medical diagnostics, treatments, and unexplored ways to monitor food quality.

Point-of-Care Platform for Diagnosis of Venous Thrombosis by Simultaneous Detection of Thrombin Generation and D-Dimer in Human Plasma.

Venous thromboembolism (VTE) refers to a blood clot that starts in a vein. The risk of developing VTE is highest after major surgery or a major injury, or when someone has heart failure, cancer, or infectious disease (e.g., COVID-19). Without prompt treatment to break up clots and prevent more from forming, VTE can restrict or block blood flow and oxygen, which can damage the body tissue or organs. VTE can occur without any obvious signs, and imaging technologies are used. Alternatively rapid measurement of thrombin generation (TG) and D-dimer could be used to make a fast, portable, and easy-to-use diagnostic platform for VTE. Here, we have demonstrated a diagnostic sensing platform with the ability of simultaneous detection of TG and D-dimer in human plasma. Modifications were made to both the assay protocols to eliminate the need for sample dilution and incubation steps. Using a substantially reduced sample volume, the measurement results show comparable performance to the gold standard method. Our platform is able to deliver accurate and cost-effective results for both TG and D-dimer assays when using undiluted plasma in under 15 min. The assays presented are therefore a good candidate technology for use in a point-of-care platform to diagnose VTE.

Factor VIII companion diagnostic for haemophilia.

Haemophilia is predominantly an inherited disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding. The condition of this disease is complex to manage, but many patients do so through home therapy and often only see their core multidisciplinary healthcare team annually. There is an increasing need for patients to be able to monitor their condition efficiently at home while staying connected with their healthcare team. As a consequence, a low-cost handheld self-monitoring solution for clotting factor is required. Here we have demonstrated a suitable one-step Factor VIII companion diagnostic sensing approach based on a chromogenic assay for haemophilia A. The results show comparable performance to the gold standard method. Our approach is able to deliver accurate cost-effective results in under 5 min from undiluted human plasma. It has the potential to be able to reduce the human and monetary costs of over- or under-medication for haemophiliacs.

A Cybersecure P300-Based Brain-to-Computer Interface against Noise-Based and Fake P300 Cyberattacks.

In a progressively interconnected world where the Internet of Things (IoT), ubiquitous computing, and artificial intelligence are leading to groundbreaking technology, cybersecurity remains an underdeveloped aspect. This is particularly alarming for brain-to-computer interfaces (BCIs), where hackers can threaten the user's physical and psychological safety. In fact, standard algorithms currently employed in BCI systems are inadequate to deal with cyberattacks. In this paper, we propose a solution to improve the cybersecurity of BCI systems. As a case study, we focus on P300-based BCI systems using support vector machine (SVM) algorithms and EEG data. First, we verified that SVM algorithms are incapable of identifying hacking by simulating a set of cyberattacks using fake P300 signals and noise-based attacks. This was achieved by comparing the performance of several models when validated using real and hacked P300 datasets. Then, we implemented our solution to improve the cybersecurity of the system. The proposed solution is based on an EEG channel mixing approach to identify anomalies in the transmission channel due to hacking. Our study demonstrates that the proposed architecture can successfully identify 99.996% of simulated cyberattacks, implementing a dedicated counteraction that preserves most of BCI functions.

A monolithic single-chip point-of-care platform for metabolomic prostate cancer detection.

There is a global unmet need for rapid and cost-effective prognostic and diagnostic tools that can be used at the bedside or in the doctor's office to reduce the impact of serious disease. Many cancers are diagnosed late, leading to costly treatment and reduced life expectancy. With prostate cancer, the absence of a reliable test has inhibited the adoption of screening programs. We report a microelectronic point-of-care metabolite biomarker measurement platform and use it for prostate cancer detection. The platform, using an array of photodetectors configured to operate with targeted, multiplexed, colorimetric assays confined in monolithically integrated passive microfluidic channels, completes a combined assay of 4 metabolites in a drop of human plasma in under 2 min. A preliminary clinical study using l-amino acids, glutamate, choline, and sarcosine was used to train a cross-validated random forest algorithm. The system demonstrated sensitivity to prostate cancer of 94% with a specificity of 70% and an area under the curve of 0.78. The technology can implement many similar assay panels and hence has the potential to revolutionize low-cost, rapid, point-of-care testing.

Disposable Paper-on-CMOS Platform for Real-Time Simultaneous Detection of Metabolites.

OBJECTIVE: Early stage diagnosis of sepsis without overburdening health services is essential to improving patient outcomes. METHODS: A fast and simple-to-use platform that combines an integrated circuit with paper microfluidics for simultaneous detection of multiple-metabolites appropriate for diagnostics was presented. Paper based sensors are a primary candidate for widespread deployment of diagnostic or test devices. However, the majority of devices today use a simple paper strip to detect a single marker using the reflectance of light. However, for many diseases such as sepsis, one biomarker is not sufficient to make a unique diagnosis. In this work multiple measurements are made on patterned paper simultaneously. Using laser ablation to fabricate microfluidic channels on paper provides a flexible and direct approach for mass manufacture of disposable paper strips. A reusable photodiode array on a complementary metal oxide semiconductor chip is used as the transducer. RESULTS: The system measures changes in optical absorbance in the paper to achieve a cost-effective and easily implemented system that is capable of multiple simultaneous assays. Potential sepsis metabolite biomarkers glucose and lactate have been studied and quantified with the platform, achieving sensitivity within the physiological range in human serum. CONCLUSION: We have detailed a disposable paper-based CMOS photodiode sensor platform for real-time simultaneous detection of metabolites for diseases such as sepsis. SIGNIFICANCE: A combination of a low-cost paper strip with microfluidic channels and a sensitive CMOS photodiode sensor array makes our platform a robust portable and inexpensive biosensing device for multiple diagnostic tests in many different applications.

Multimodal Integrated Sensor Platform for Rapid Biomarker Detection.

Precision metabolomics and quantification for cost-effective rapid diagnosis of disease are the key goals in personalized medicine and point-of-care testing. At present, patients are subjected to multiple test procedures requiring large laboratory equipment. Microelectronics has already made modern computing and communications possible by integration of complex functions within a single chip. As More than Moore technology increases in importance, integrated circuits for densely patterned sensor chips have grown in significance. Here, we present a versatile single complementary metal-oxide-semiconductor chip forming a platform to address personalized needs through on-chip multimodal optical and electrochemical detection that will reduce the number of tests that patients must take. The chip integrates interleaved sensing subsystems for quadruple-mode colorimetric, chemiluminescent, surface plasmon resonance, and hydrogen ion measurements. These subsystems include a photodiode array and a single photon avalanche diode array with some elements functionalized to introduce a surface plasmon resonance mode. The chip also includes an array of ion sensitive field-effect transistors. The sensor arrays are distributed uniformly over an active area on the chip surface in a scalable and modular design. Bio-functionalization of the physical sensors yields a highly selective simultaneous multiple-assay platform in a disposable format. We demonstrate its versatile capabilities through quantified bio-assays performed on-chip for glucose, cholesterol, urea, and urate, each within their naturally occurring physiological range.