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)

A Biosensor-CMOS Platform and Integrated Readout Circuit in 0.18-μm CMOS Technology for Cancer Biomarker Detection

This paper presents a biosensor-CMOS platform for measuring the capacitive coupling of biorecognition elements. The biosensor is designed, fabricated, and tested for the detection and quantification of a protein that reveals the presence of early-stage cancer. For the first time, the spermidine/spermine N1 acetyltransferase (SSAT) enzyme has been screened and quantified on the surface of a capacitive sensor. The sensor surface is treated to immobilize antibodies, and the baseline capacitance of the biosensor is reduced by connecting an array of capacitors in series for fixed exposure area to the analyte. A large sensing area with small baseline capacitance is implemented to achieve a high sensitivity to SSAT enzyme concentrations. The sensed capacitance value is digitized by using a 12-bit highly digital successive-approximation capacitance-to-digital converter that is implemented in a 0.18 μm CMOS technology. The readout circuit operates in the near-subthreshold regime and provides power and area efficient operation. The capacitance range is 16.137 pF with a 4.5 fF absolute resolution, which adequately covers the concentrations of 10 mg/L, 5 mg/L, 2.5 mg/L, and 1.25 mg/L of the SSAT enzyme. The concentrations were selected as a pilot study, and the platform was shown to demonstrate high sensitivity for SSAT enzymes on the surface of the capacitive sensor. The tested prototype demonstrated 42.5 μS of measurement time and a total power consumption of 2.1 μW

On Chip Counting and Localisation of Magnetite Pollution Nanoparticles

Magnetic nanoparticles are generally smaller than 200 nm surrounding our environment and can easily enter the human brain through the respiratory system. The harm of such nanoparticles may endanger people’s health. This paper focuses on modelling and simulation based on a new kind of magnetic sensors, which can count and localize these magnetite nanoparticles. The proposed sensors could help to prevent these nanoparticles from the polluted environment and undoubtedly reduce their adverse risks to humans. The modelled magnetic system consists of a tunnelling magnetoresistive (TMR) sensor array, a conducting line, and the detected magnetite nanoparticles. The localization and quantization of these nanoparticles can be achieved by analysing total output voltages from the TMR sensor array

A CMOS Analog Front-End for Tunnelling Magnetoresistive Spintronic Sensing Systems

This paper presents a CMOS readout circuit for an integrated and highly-sensitive tunnel-magnetoresistive (TMR) sensor. Based on the characterization of the TMR sensor in the finite-element simulation, using COMSOL Multiphysics, the circuit including a Wheatstone bridge and an analogue front-end (AFE) circuit, were designed to achieve low-noise and low-power sensing. We present a transimpedance amplifier (TIA) that biases and amplifies a TMR sensor array using switched-capacitors external noise filtering and allows the integration of TMR sensors on CMOS without decreasing the measurement resolution. Designed using TSMC 0.18 μm 1V technology, the amplifier consumes 160 nA at 1.8 V supply to achieve a dc gain of 118 dB and a bandwidth of 3.8 MHz. The results confirm that the full system is able to detect the magnetic field in the pico-Tesla range with low circuit noise (2.297 pA/√Hz) and low power consumption (86 μW). A concurrent reduction in the power consumption and attenuation of noise in TMR sensors makes them suitable for long-term deployment in spintronic sensing systems

Interface Circuits for Microsensor Integrated Systems

ca. 200 words; this text will present the book in all promotional forms (e.g. flyers). Please describe the book in straightforward and consumer-friendly terms. [Recent advances in sensing technologies, especially those for Microsensor Integrated Systems, have led to several new commercial applications. Among these, low voltage and low power circuit architectures have gained growing attention, being suitable for portable long battery life devices. The aim is to improve the performances of actual interface circuits and systems, both in terms of voltage mode and current mode, in order to overcome the potential problems due to technology scaling and different technology integrations. Related problems, especially those concerning parasitics, lead to a severe interface design attention, especially concerning the analog front-end and novel and smart architecture must be explored and tested, both at simulation and prototype level. Moreover, the growing demand for autonomous systems gets even harder the interface design due to the need of energy-aware cost-effective circuit interfaces integrating, where possible, energy harvesting solutions. The objective of this Special Issue is to explore the potential solutions to overcome actual limitations in sensor interface circuits and systems, especially those for low voltage and low power Microsensor Integrated Systems. The present Special Issue aims to present and highlight the advances and the latest novel and emergent results on this topic, showing best practices, implementations and applications. The Guest Editors invite to submit original research contributions dealing with sensor interfacing related to this specific topic. Additionally, application oriented and review papers are encouraged.

The potential of microelectrode arrays and microelectronics for biomedical research and diagnostics

Planar microelectrode arrays (MEAs) are devices that can be used in biomedical and basic in vitro research to provide extracellular electrophysiological information about biological systems at high spatial and temporal resolution. Complementary metal oxide semiconductor (CMOS) is a technology with which MEAs can be produced on a microscale featuring high spatial resolution and excellent signal-to-noise characteristics. CMOS MEAs are specialized for the analysis of complete electrogenic cellular networks at the cellular or subcellular level in dissociated cultures, organotypic cultures, and acute tissue slices; they can also function as biosensors to detect biochemical events. Models of disease or the response of cellular networks to pharmacological compounds can be studied in vitro, allowing one to investigate pathologies, such as cardiac arrhythmias, memory impairment due to Alzheimer's disease, or vision impairment caused by ganglion cell degeneration in the retin

Bidirectional Neural Interface Circuits with On-Chip Stimulation Artifact Reduction Schemes

Bidirectional neural interfaces are tools designed to “communicate” with the brain via recording and modulation of neuronal activity. The bidirectional interface systems have been adopted for many applications. Neuroscientists employ them to map neuronal circuits through precise stimulation and recording. Medical doctors deploy them as adaptable medical devices which control therapeutic stimulation parameters based on monitoring real-time neural activity. Brain-machine-interface (BMI) researchers use neural interfaces to bypass the nervous system and directly control neuroprosthetics or brain-computer-interface (BCI) spellers. In bidirectional interfaces, the implantable transducers as well as the corresponding electronic circuits and systems face several challenges. A high channel count, low power consumption, and reduced system size are desirable for potential chronic deployment and wider applicability. Moreover, a neural interface designed for robust closed-loop operation requires the mitigation of stimulation artifacts which corrupt the recorded signals. This dissertation introduces several techniques targeting low power consumption, small size, and reduction of stimulation artifacts. These techniques are implemented for extracellular electrophysiological recording and two stimulation modalities: direct current stimulation for closed-loop control of seizure detection/quench and optical stimulation for optogenetic studies. While the two modalities differ in their mechanisms, hardware implementation, and applications, they share many crucial system-level challenges. The first method aims at solving the critical issue of stimulation artifacts saturating the preamplifier in the recording front-end. To prevent saturation, a novel mixed-signal stimulation artifact cancellation circuit is devised to subtract the artifact before amplification and maintain the standard input range of a power-hungry preamplifier. Additional novel techniques have been also implemented to lower the noise and power consumption. A common average referencing (CAR) front-end circuit eliminates the cross-channel common mode noise by averaging and subtracting it in analog domain. A range-adapting SAR ADC saves additional power by eliminating unnecessary conversion cycles when the input signal is small. Measurements of an integrated circuit (IC) prototype demonstrate the attenuation of stimulation artifacts by up to 42 dB and cross-channel noise suppression by up to 39.8 dB. The power consumption per channel is maintained at 330 nW, while the area per channel is only 0.17 mm2. The second system implements a compact headstage for closed-loop optogenetic stimulation and electrophysiological recording. This design targets a miniaturized form factor, high channel count, and high-precision stimulation control suitable for rodent in-vivo optogenetic studies. Monolithically integrated optoelectrodes (which include 12 µLEDs for optical stimulation and 12 electrical recording sites) are combined with an off-the-shelf recording IC and a custom-designed high-precision LED driver. 32 recording and 12 stimulation channels can be individually accessed and controlled on a small headstage with dimensions of 2.16 x 2.38 x 0.35 cm and mass of 1.9 g. A third system prototype improves the optogenetic headstage prototype by furthering system integration and improving power efficiency facilitating wireless operation. The custom application-specific integrated circuit (ASIC) combines recording and stimulation channels with a power management unit, allowing the system to be powered by an ultra-light Li-ion battery. Additionally, the µLED drivers include a high-resolution arbitrary waveform generation mode for shaping of µLED current pulses to preemptively reduce artifacts. A prototype IC occupies 7.66 mm2, consumes 3.04 mW under typical operating conditions, and the optical pulse shaping scheme can attenuate stimulation artifacts by up to 3x with a Gaussian-rise pulse rise time under 1 ms.PHDElectrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/147674/1/mendrela_1.pd

Electrostatic Discharge

As we enter the nanoelectronics era, electrostatic discharge (ESD) phenomena is an important issue for everything from micro-electronics to nanostructures. This book provides insight into the operation and design of micro-gaps and nanogenerators with chapters on low capacitance ESD design in advanced technologies, electrical breakdown in micro-gaps, nanogenerators from ESD, and theoretical prediction and optimization of triboelectric nanogenerators. The information contained herein will prove useful for for engineers and scientists that have an interest in ESD physics and design

A Fully Integrated CMOS Receiver.

The rapidly growing wireless communication market is creating an increasing demand for low-cost highly-integrated radio frequency (RF) communication systems. This dissertation focuses on techniques to enable fully-integrated, wireless receivers incorporating all passive components, including the antenna, and also incorporating baseband synchronization on-chip. Not only is the receiver small in size and requires very low power, but it also delivers synchronized demodulated data. This research targets applications such as implantable neuroprosthetic devices and environmental wireless sensors, which need short range, low data-rate wireless communications but a long lifetime. To achieve these goals, the super-regenerative architecture is used, since power consumption with this architecture is low due to the simplified receiver architecture. This dissertation presents a 5GHz single chip receiver incorporating a compact on-chip 5 GHz slot antenna (50 times smaller than traditional dipole antennas) and a digital received data synchronization. A compact capacitively-loaded 5 GHz standing-wave resonator is used to improve the energy efficiency. An all-digital PLL timing scheme synchronizes the received data clock. A new type of low-power envelope detector is incorporated to increase the data rate and efficiency. The receiver achieves a data rate up to 1.2 Mb/s, dissipates 6.6 mW from a 1.5 V supply. The novel on-chip capacitively-loaded, transmission-line-standing-wave resonator is employed instead of a conventional low-Q on-chip inductor. The simulated quality factor of the resonator is very high (35), and is verified by phase-noise measurements of a prototype 5GHz Voltage Control Oscillator (VCO) incorporating this resonator. The prototype VCO, implemented in 0.13 µm CMOS, dissipates 3 mW from a 1.2 V supply, and achieves a measured phase noise of -117 dBc/Hz at a 1 MHz offset. In the on-chip antenna an efficient shielding technique is used to shield the antenna from the low-resistivity substrate underneath. Two standalone on-chip slot antenna prototypes were designed and fabricated in 0.13 µm CMOS. The 9 GHz prototype occupies a die area of only 0.3 mm2, has an active gain of -4.4 dBi and an efficiency of 9%. The second prototype occupies a die area of 0.47 mm2, and achieves a passive gain of approximately -17.0 dBi at 5 GHz.Ph.D.Electrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/60739/1/shid_1.pd

An Integrated ISFET Sensor Array

A monolithically integrated ISFET sensor array and interface circuit are described. A new high-density, low-power source-drain follower was developed for the sensor array. ISFETs were formed by depositing Au/Ti extended-gate electrodes on standard MOSFETs, then thin silicon nitride layers using catalytic chemical vapor deposition and/or SU-8 protective layers were formed on the extended-gate electrodes. Applications for the array include: (1) pH detection by statistical distribution observing time and space fluctuations; (2) DNA detection using thiol-modified or silane-coupled oligonucleotides; (3) bio-image sensing by converting photons to electrons using Photosystem I of Thermosynechococcus elongatus, and sensing the converted electric charges by ISFETs