Design of a CMOS closed-loop system with applications to bio-impedance measurements

This paper proposes a method for impedance measurements based on a closed-loop implementation of CMOS circuits. The proposed system has been conceived for alternate current excited systems, performing simultaneously driving and measuring functions, thanks to feedback. The system delivers magnitude and phase signals independently, which can be optimized separately, and can be applied to any kind of load (resistive and capacitive). Design specifications for CMOS circuit blocks and trade-offs for system accuracy and loop stability have been derived. Electrical simulation results obtained for several loads agree with the theory, enabling the proposed method to any impedance measurement problem, in special, to bio-setups including electrodes.Ministerio de Ciencia e Innovación TEC2007-6807

A microscopy technique based on bio-impedance sensors

It is proposed a microscopy for cell culture applications based on impedance sensors. The imagined signals are measured with the Electrical Cell-Substrate Spectroscopy (ECIS) technique, by identifying the cell area. The proposed microscopy allows real-time monitoring inside the incubator, reducing the contamination risk by human manipulation. It requires specific circuits for impedance measurements, a two-dimensional sensor array (pixels), and employing electrical models to decode efficiently the measured signals. Analogue Hardware Description Language (AHDL) circuits for cell-microelectrode enables the use of geometrical and technological data into the system design flow. A study case with 8x8 sensor array is reported, illustrating the evolution and power of the proposed image acquisition.Junta de Andalucía P0-TIC-538

Sensing Cell-Culture Assays with Low-Cost Circuitry

An alternative approach for cell-culture end-point protocols is proposed herein. This new technique is suitable for real-time remote sensing. It is based on Electrical Cell-substrate Impedance Spectroscopy (ECIS) and employs the Oscillation-Based Test (OBT) method. Simple and straightforward circuit blocks form the basis of the proposed measurement system. Oscillation parameters – frequency and amplitude – constitute the outcome, directly correlated with the culture status. A user can remotely track the evolution of cell cultures in real time over the complete experiment through a web tool continuously displaying the acquired data. Experiments carried out with commercial electrodes and a well-established cell line (AA8) are described, obtaining the cell number in real time from growth assays. The electrodes have been electrically characterized along the design flow in order to predict the system performance and the sensitivity curves. Curves for 1-week cell growth are reported. The obtained experimental results validate the proposed OBT for cell-culture characterization. Furthermore, the proposed electrode model provides a good approximation for the cell number and the time evolution of the studied cultures.España, Feder TEC2013-46242-C3-1-

A neural probe with up to 966 electrodes and up to 384 configurable channels in 0.13 μm SOI CMOS

In vivo recording of neural action-potential and local-field-potential signals requires the use of high-resolution penetrating probes. Several international initiatives to better understand the brain are driving technology efforts towards maximizing the number of recording sites while minimizing the neural probe dimensions. We designed and fabricated (0.13-μm SOI Al CMOS) a 384-channel configurable neural probe for large-scale in vivo recording of neural signals. Up to 966 selectable active electrodes were integrated along an implantable shank (70 μm wide, 10 mm long, 20 μm thick), achieving a crosstalk of −64.4 dB. The probe base (5 × 9 mm2) implements dual-band recording and a 1

Generation of HDL models for bio-impedance sensor simulation based on microelectrodes

This paper presents a computer tool for automatic analysis of cell culture images. The program allows the extraction of relevant information from biological images for pre and post system analysis. In particular, this tool is being used for electrical characterization of electrode-solution-cell systems in which bio-impedance is the main parameter to be known. The correct modeling of this kind of systems enables both electronic system characterization for circuit design specifications and data decoding from measurements. The developed program allows cell culture image processing for geographic information extraction and sensor sizing, generating cell count and Analog Hardware Description Language (AHDL) equivalent circuits useful for whole system simulations

Towards Bio-impedance Based Labs: A Review

In this article, some of the main contributions to BI (Bio-Impedance) parameter-based systems for medical, biological and industrial fields, oriented to develop micro laboratory systems are summarized. These small systems are enabled by the development of new measurement techniques and systems (labs), based on the impedance as biomarker. The electrical properties of the life mater allow the straightforward, low cost and usually non-invasive measurement methods to define its status or value, with the possibility to know its time evolution. This work proposes a review of bio-impedance based methods being employed to develop new LoC (Lab-on-a-Chips) systems, and some open problems identified as main research challenges, such as, the accuracy limits of measurements techniques, the role of the microelectrode-biological impedance modeling in measurements and system portability specifications demanded for many applications.Spanish founded Project: TEC 2013-46242-C3-1-P: Integrated Microsystem for Cell Culture AssaysFEDE

Cell-Culture Measurements Using Voltage Oscillations

A comprehensive system for real-time monitoring of a set of cell-cultures using a Voltage Oscillation (VO) methodology is proposed. The main idea is to connect the bio-electrical elements (electrodes & cell-culture) in such a way that sequentially a suitable electrical oscillator, which only uses a DC power source, is built. Using the employed electrical models given in [1, 2], the attained oscillation parameters (frequency and amplitude) can be directly related to the biological test. A digital circuitry is developed to pick-up the experimental measurements, which are gathered and shown in real-time in a web application.Ministerio de Economía y Competitividad TEC2013-46242-C3-1-

A Sinusoidal Current Driver With an Extended Frequency Range and Multifrequency Operation for Bioimpedance Applications

This paper describes an alternative sinusoidal current driver suitable for bioimpedance applications where high frequency operation is required. The circuit is based on a transconductor and provides current outputs with low phase error for frequencies around its pole frequency. This extends the upper frequency operational limit of the current driver. Multifrequency currents can be generated where each individual frequency is phase corrected. Analysis of the circuit is presented together with simulation and experimental results which demonstrate the proof of concept for both single and dual frequency current drivers. Measurements on a discrete test version of the circuit demonstrate a phase reduction from 25 ^{\circ} to 4 ^{\circ} at 3 MHz for 2 mAp-p output current. The output impedance of the current driver is essentially constant at about 1.1 M \Omega over a frequency range of 100 kHz to 5 MHz due to the introduction of the phase compensation. The compensation provides a bandwidth increase of a factor of about six for a residual phase delay of 4 ^{\circ

High-power CMOS current driver with accurate transconductance for electrical impedance tomography

Current drivers are fundamental circuits in bioimpedance measurements including electrical impedance tomography (EIT). In the case of EIT, the current driver is required to have a large output impedance to guarantee high current accuracy over a wide range of load impedance values. This paper presents an integrated current driver which meets these requirements and is capable of delivering large sinusoidal currents to the load. The current driver employs a differential architecture and negative feedback, the latter allowing the output current to be accurately set by the ratio of the input voltage to a resistor value. The circuit was fabricated in a 0.6-μ m high-voltage CMOS process technology and its core occupies a silicon area of 0.64 mm2. It operates from a ± 9 V power supply and can deliver output currents up to 5 mA p-p. The accuracy of the maximum output current is within 0.41% up to 500 kHz, reducing to 0.47% at 1 MHz with a total harmonic distortion of 0.69%. The output impedance is 665 kΩ at 100 kHz and 372 k Ω at 500 kHz