Novel Readout Circuit for Memristive Biosensors in Cancer Detection

We present a novel circuit for the automated and quick characterization of an array of experimental memristive nanowires that are functionalized as biosensors. Successfully functionalized nanowires will express the concentration of target molecules by hysteretic gaps of the zero crossing of their mem- ristive I/V characteristics as the voltage across them is swept up and down. The width of the voltage gap is directly proportional to the target molecule concentration. The characterization circuit sorts out faulty, i.e. non-conducting nanowires in the array, and performs an analog to digital conversion of the voltage gap to assess successful functionalization of the others, and thus significantly reduces the time for functional testing. Many of the test parameters are configurable: the speed and range of the voltage sweep and the resolution of the measurements. An initial prototype 2x2 array of the circuit has been layed out in 0.35μm CMOS technology within an area of 0.429 mm2 and has been thoroughly characterized in simulation, has been layed out, and is ready for fabrication

SiNW-based Biosensors for Profiling Biomarkers in Breast Tumor Tissues

Breast cancer is the most common life-threatening malignancy in women of most developed countries today, with approximately 200,000 new cases diagnosed every year. About 30% of these cases progress to metastatic disease and death. Considering that one-third of these cancer deaths could be decreased if detected and treated early, new strategies for early breast cancer detection are needed to improve the efficacy of current diagnostics. The sensitive analysis of proteins such as breast cancer biomarkers has become the focus of intensive research due to its relevance to tumor diagnosis. However, the state-of-the-art diagnostic tools still lack the level of resolution needed for the detection of biomarkers at the very early stage of the disease, when treatments have more probability of success, and when protein concentration in tumor tissue is still very low. Nanotechnologies have shown great potential for the development of high-sensitive, portable devices for clinical applications. In particular, SiNWs with their unique properties such as the high surface-to-volume ratio and size, combined with the specificity of immune-sensing, are natural candidates for the fabrication of nanosensors. Thanks to their compatibility with conventional CMOS technology, SiNWs have been incorporated in standard FETs. In biosensing, SiNW-FETs have been shown a promising method for the label-free detection of trace amounts of biomolecules. However, detection of Antigen using Antibody immobilized SiNW-FETs is limited by ionic screening effects that reduce the sensor responsiveness and limit their applicability in tumor tissue. Here, we propose novel SiNW-based biosensing strategies with the aim of overcoming current sensitivity limitations of conventional SiNW-FET biosensors for the detection of breast cancer biomarkers in real human samples. Specifically, we address this goal by investigating two different approaches of biosensing. In the first method, we push the sensitivity of SiNW-FETs to their limits by proposing an alternative way of doing sensing in dry conditions. We show that in-air electrical measurements of Ab-Ag binding have the big advantage of increased Debye screening length in non-bulk solutions, and enable highly sensitive and specific measurements in breast tumor extract. Then, we present a completely novel biosensing paradigm that shows, for the first time, the use of memristive effects in fabricated SiNWs for biodetection purposes. This novel detection method has been named Voltage Gap (VoG)-biosensing as it is based on the changes of the VoG parameter, observed in the hysteretic characteristic of memristive devices, as a function of biomolecules. In this research, we demonstrate the use of the memristive-based VoG effect in Schottky Barrier SiNWs for the high-resolution sensing of ionic and biological species both in ideal buffer solutions and in tumor tissue extracts. Moreover, we propose an original theory enabling the physical interpretation and prediction of the mechanisms underlying the VoG-biosensing method in memristive devices. Finally, we demonstrate the potential of our system for future integration in a multi-panel VoG-biosensing platform. We fabricated a PDMS microfluidics enabling selective and high-quality functionalization of the NWs. We also realized a CMOS readout circuit for multiplexed VoG acquisition. The simulations demonstrate the feasibility of the approach and the potential for the integration of the reader with a portable and automated biosensing platform. Microfluidics and VoG reader will enable fast, concurrent detection ofmultiple angiogenic and inflammatory ligands in tumor tissue. This will highly improve the level of knowledge of the cancer disease by capturing the heterogeneity and the complexity of the tumor microenvironment, thus leading to novel opportunities in breast cancer diagnosis

Label-Free Ultrasensitive Memristive Aptasensor

We present the very first worldwide ever-reported electrochemical biosensor based on a memristive effect and DNA aptamers. This novel device is developed to propose a completely new approach in cancer diagnostics. In this study, an affinity-based technique is presented for the detection of the prostate specific antigen (PSA) using DNA aptamers. The hysteretic properties of memristive silicon nanowires functionalized with these DNA aptamers provide a label-free and ultrasensitive biodetection technique. The ultrasensitive detection is hereby demonstrated for PSA with a limit of detection down to 23 aM, best ever published value for electrochemical biosensors in PSA detection. The effect of polyelectrolytes on our memristive devices is also reported to further show how positive or negative charges affect the memristive hysteresis. With such an approach, combining memristive nanowires and aptamers, memristive aptamer-based biosensors can be proposed to detect a wide range of cancer markers with unprecedent ultrasensitivities to also address the issue of an early detection of cancer

Memristive Biosensors Under Varying Humidity Conditions

We attempt to examine the potential of silicon nanowire memristors in the field of nanobiosensing. The mem- ristive devices are crystalline Silicon (Si) Nanowires (NWs) with Nickel Silicide (NiSi) terminals. The nanowires are fabricated on a Silicon-on-Insulator (SOI) wafer by an Ebeam Lithography Technique (EBL) process that allows high resolution at the nanoscale. A Deep Reactive Ion Etching (DRIE) technique is used to define free-standing nanowires. The close alignment between Silicon (Si) and Nickel-Silicide (NiSi) terminals forms a Schottky- barrier at their junction. The memristive effect of the fabricated devices matches well with the memristor theory. An equivalent circuit reproducing the memristive effect in current-voltage (I- V) characteristics of our silicon nanowires is presented too. The memristive silicon nanowire devices are then functionalized with anti-human VEGF (Vascular Endothelial Growth Factor) antibody and I-V characteristics are examined for the nanowires prior to and after protein functionalization. The uptake of bio- molecules linked to the surface of the memristive NWs is con- firmed by the increased voltage gap in the hysteresis curve. The effects of varying humidity conditions on the conductivity of bio- modified memristive silicon nanowires are deeply investigate

Organic Bioelectronics Development in Italy: A Review

In recent years, studies concerning Organic Bioelectronics have had a constant growth due to the interest in disciplines such as medicine, biology and food safety in connecting the digital world with the biological one. Specific interests can be found in organic neuromorphic devices and organic transistor sensors, which are rapidly growing due to their low cost, high sensitivity and biocompatibility. This trend is evident in the literature produced in Italy, which is full of breakthrough papers concerning organic transistors-based sensors and organic neuromorphic devices. Therefore, this review focuses on analyzing the Italian production in this field, its trend and possible future evolutions

Adaptive extreme edge computing for wearable devices

Wearable devices are a fast-growing technology with impact on personal healthcare for both society and economy. Due to the widespread of sensors in pervasive and distributed networks, power consumption, processing speed, and system adaptation are vital in future smart wearable devices. The visioning and forecasting of how to bring computation to the edge in smart sensors have already begun, with an aspiration to provide adaptive extreme edge computing. Here, we provide a holistic view of hardware and theoretical solutions towards smart wearable devices that can provide guidance to research in this pervasive computing era. We propose various solutions for biologically plausible models for continual learning in neuromorphic computing technologies for wearable sensors. To envision this concept, we provide a systematic outline in which prospective low power and low latency scenarios of wearable sensors in neuromorphic platforms are expected. We successively describe vital potential landscapes of neuromorphic processors exploiting complementary metal-oxide semiconductors (CMOS) and emerging memory technologies (e.g. memristive devices). Furthermore, we evaluate the requirements for edge computing within wearable devices in terms of footprint, power consumption, latency, and data size. We additionally investigate the challenges beyond neuromorphic computing hardware, algorithms and devices that could impede enhancement of adaptive edge computing in smart wearable devices