Analytical and numerical modeling methods for impedance analysis of single cells on-chip

Electrical impedance spectroscopy (EIS) is a noninvasive method for characterizing the dielectric properties of biological particles. The technique can differentiate between cell types and provide information on cell properties through measurement of the permittivity and conductivity of the cell membrane and cytoplasm. In terms of lab-on-a-chip (LOC) technology, cells pass sequentially through the microfluidic channel at high speed and are analyzed individually, rather than as traditionally done on a mixture of particles in suspension. This paper describes the analytical and numerical modeling methods for EIS of single cell analysis in a microfluidic cytometer. The presented modeling methods include Maxwell’s mixture theory, equivalent circuit model and finite element method. The difference and advantages of these methods have been discussed. The modeling work has covered the static case — an immobilized cell in suspension and the dynamic case — a moving cell in the channel

Phase-Coherent Dynamics of a Superconducting Flux Qubit with Capacitive-Bias Readout

We present a systematic study of the phase-coherent dynamics of a superconducting three-Josephson-junction flux qubit. The qubit state is detected with the integrated-pulse method, which is a variant of the pulsed switching DC SQUID method. In this scheme the DC SQUID bias current pulse is applied via a capacitor instead of a resistor, giving rise to a narrow band-pass instead of a pure low-pass filter configuration of the electromagnetic environment. Measuring one and the same qubit with both setups allows a direct comparison. With the capacitive method about four times faster switching pulses and an increased visibility are achieved. Furthermore, the deliberate engineering of the electromagnetic environment, which minimizes the noise due to the bias circuit, is facilitated. Right at the degeneracy point the qubit coherence is limited by energy relaxation. We find two main noise contributions. White noise is limiting the energy relaxation and contributing to the dephasing far from the degeneracy point. 1/f-noise is the dominant source of dephasing in the direct vicinity of the optimal point. The influence of 1/f-noise is also supported by non-random beatings in the Ramsey and spin echo decay traces. Numeric simulations of a coupled qubit-oscillator system indicate that these beatings are due to the resonant interaction of the qubit with at least one point-like fluctuator, coupled especially strongly to the qubit.Comment: Minor changes. 21 pages, 15 figure

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)

Energy-Efficient PRBS Impedance Spectroscopy on a Digital Versatile Platform

partially_open6siThis research has been partially funded by the Italian Ministry of University and Research (MUR) through the program “Dipartimenti di Eccellenza” (2018-2022). The research has also received partial support from the Italian Ministry of University and Research (MUR) and the Eranet FLAG ERA initiative within CONVERGENCE project (CUP B84I16000030005) through the IUNET Consortium.This paper presents the digital design of a versatile and low-power broadband impedance spectroscopy (IS) system based on pseudo-random binary sequence (PRBS) excitation. The PRBS technique allows fast, and low-power estimation of the impedance spectrum over a wide bandwidth with adequate accuracy, proving to be a good candidate for portable medical devices, especially. This paper covers the low-power design of the firmware algorithms and implements them on a versatile and reconfigurable digital platform that can be easily adjusted to the specific application. It will analyze the digital platform with the aim of reducing power consumption while maintaining adequate accuracy of the estimated spectrum. The paper studies two main algorithms (time-domain and frequency-domain) used for PRBS-based IS and implements both of them on the ultra-low-power GAP-8 digital platform. They are compared in terms of accuracy, measurement time, and power budget, while general design trade-offs are drawn out. The time-domain algorithm demonstrated the best accuracy while the frequency-domain one contributes more to save power and energy. However, analysis of the energy-per-error FOM revealed that the time-domain algorithm outperforms the frequency-domain algorithm offering better accuracy for the same energy consumption. Numerical methods and microprocessor resources are exploited to optimize the implementation of both algorithms achieving 27 ms in processing time, power consumption as low as 1.4 mW and a minimum energy consumption per measurement of 0.5 mJ, for a dense impedance spectrum estimation of 214 points.embargoed_20210525Luciani G.; Crescentini M.; Romani A.; Chiani M.; Benini L.; Tartagni M.Luciani G.; Crescentini M.; Romani A.; Chiani M.; Benini L.; Tartagni M

When self-consistency makes a difference

Compound semiconductor power RF and microwave device modeling requires, in many cases, the use of selfconsistent electrothermal equivalent circuits. The slow thermal dynamics and the thermal nonlinearity should be accurately included in the model; otherwise, some response features subtly related to the detailed frequency behavior of the slow thermal dynamics would be inaccurately reproduced or completely distorted. In this contribution we show two examples, concerning current collapse in HBTs and modeling of IMPs in GaN HEMTs. Accurate thermal modeling is proved to be be made compatible with circuit-oriented CAD tools through a proper choice of system-level approximations; in the discussion we exploit a Wiener approach, but of course the strategy should be tailored to the specific problem under consideratio

Towards CMOS Nuclear Magnetic Resonance Spectroscopy: Design, Implementation and Experimental Results

Nuclear Magnetic Resonance (NMR) Spectroscopy is used intensively along with other ancillary spectroscopic and characterization techniques. The design and implementation of High Throughput NMR Spectroscopy is a key challenge to accelerate the drug discovery process. On the other hand, the current conventional NMR technologies are expensive and bulky. The development of novel handheld NMR spectroscopy is a key challenge towards NMR spectroscopy for Point-of-Care (PoC) diagnostics applications. This thesis addresses the above-mentioned challenges of High Throughput NMR Spectroscopy and Handheld NMR spectroscopy by developing new integrated circuits dedicated to NMR spectroscopy using Complementary Metal Oxide Semiconductor (CMOS) technology. Simulation and characterization results were also used to prove the functionality and applicability of the proposed techniques. We have designed two CMOS chips using 0.13-m technology, first chip includes number of new vertical microcoils and LNA with 780 pV/Hz at 300 MHz and the second one is a new dual-path NMR receiver

Electrochemical Sensors and On-chip Optical Sensors

abstract: The microelectronics technology has seen a tremendous growth over the past sixty years. The advancements in microelectronics, which shows the capability of yielding highly reliable and reproducible structures, have made the mass production of integrated electronic components feasible. Miniaturized, low-cost, and accurate sensors became available due to the rise of the microelectronics industry. A variety of sensors are being used extensively in many portable applications. These sensors are promising not only in research area but also in daily routine applications. However, many sensing systems are relatively bulky, complicated, and expensive and main advantages of new sensors do not play an important role in practical applications. Many challenges arise due to intricacies for sensor packaging, especially operation in a solution environment. Additional problems emerge when interfacing sensors with external off-chip components. A large amount of research in the field of sensors has been focused on how to improve the system integration. This work presents new methods for the design, fabrication, and integration of sensor systems. This thesis addresses these challenges, for example, interfacing microelectronic system to a liquid environment and developing a new technique for impedimetric measurement. This work also shows a new design for on-chip optical sensor without any other extra components or post-processing.Dissertation/ThesisDoctoral Dissertation Electrical Engineering 201