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Silicon-Based Integrated Label-Free Optofluidic Biosensors: Latest Advances and Roadmap
By virtue of the well-developed micro- and nanofabrication technologies and rapidly progressing surface functionalization strategies, silicon-based devices have been widely recognized as a highly promising platform for the next-generation lab-on-a-chip bioanalytical systems with a great potential for point-of-care medical diagnostics. Herein, an overview of the latest advances in silicon-based integrated optofluidic label-free biosensing technologies relying on the efficient interactions between the evanescent light field at the functionalized surface and specifically bound analytes is presented. State-of-the-art technologies demonstrating label-free evanescent wave-based biomarker detection mainly encompass three device configurations, including on-chip waveguide-based interferometers, microring resonators, and photonic-crystal-based cavities. Moreover, up-to-date strategies for elevating the sensitivities and also simplifying the sensing processes are discussed. Emerging laboratory prototypes with advanced integration and packaging schemes incorporating automatic microfluidic components or on-chip optoelectronic devices lead to one significant step forward in real applications of decentralized diagnostics. Besides, particular attention is paid to currently commercialized label-free optical bioanalytical models on the market. Finally, the prospects are elaborated with several research routes toward chip-scale, low-cost, highly sensitive, multi-functional, and user-friendly bioanalytical systems benefiting to global healthcare. © 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei
A handheld high-sensitivity micro-NMR CMOS platform with B-field stabilization for multi-type biological/chemical assays
We report a micro-nuclear magnetic resonance (NMR) system compatible with multi-type biological/chemical lab-on-a-chip assays. Unified in a handheld scale (dimension: 14 x 6 x 11 cm³, weight: 1.4 kg), the system is capable to detect<100 pM of Enterococcus faecalis derived DNA from a 2.5 μL sample. The key components are a portable magnet (0.46 T, 1.25 kg) for nucleus magnetization, a system PCB for I/O interface, an FPGA for system control, a current driver for trimming the magnetic (B) field, and a silicon chip fabricated in 0.18 μm CMOS. The latter, integrated with a current-mode vertical Hall sensor and a low-noise readout circuit, facilitates closed-loop B-field stabilization (2 mT → 0.15 mT), which otherwise fluctuates with temperature or sample displacement. Together with a dynamic-B-field transceiver with a planar coil for micro-NMR assay and thermal control, the system demonstrates: 1) selective biological target pinpointing; 2) protein state analysis; and 3) solvent-polymer dynamics, suitable for healthcare, food and colloidal applications, respectively. Compared to a commercial NMR-assay product (Bruker mq-20), this platform greatly reduces the sample consumption (120x), hardware volume (175x), and weight (96x)
Field Effect Transistor Nanosensor for Breast Cancer Diagnostics
Silicon nanochannel field effect transistor (FET) biosensors are one of the most promising technologies in the development of highly sensitive and label-free analyte detection for cancer diagnostics. With their exceptional electrical properties and small dimensions, silicon nanochannels are ideally suited for extraordinarily high sensitivity. In fact, the high surface-to-volume ratios of these systems make single molecule detection possible. Further, FET biosensors offer the benefits of high speed, low cost, and high yield manufacturing, without sacrificing the sensitivity typical for traditional optical methods in diagnostics. Top down manufacturing methods leverage advantages in Complementary Metal Oxide Semiconductor (CMOS) technologies, making richly multiplexed sensor arrays a reality. Here, we discuss the fabrication and use of silicon nanochannel FET devices as biosensors for breast cancer diagnosis and monitoring
Characterization-Based Modeling of Retriggering and Afterpulsing for Passively Quenched CMOS SPADs
The current trend in the design of systems based on CMOS SPADs is to adopt smaller technological nodes, allowing the co-integration of additional electronics for the implementation of complex digital systems on chip. Due to their simplicity, a way to reduce the area occupied by the integrated electronics is the use of passive quenching circuits (PQCs) instead of active (AQCs) or mixed (MQCs) ones. However, the recharge phase in PQCs is slower, so the device can be retriggered before this phase ends. This paper studies the phenomena of afterpulsing and retriggering, depending on the characteristics of the SPADs and the working conditions. In order to do that, a test chip containing SPADs of different size has been characterized in several operating environments. A mathematical model has been proposed for fitting afterpulsing phenomenon. It is shown that retriggering can be also described in terms of this model, suggesting that it is linked to carriers trapped in the shallow levels of the semiconductor and that should be taken into account when considering the total amount of afterpulsing events.Junta de Andalucía TIC 233
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