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

Characterization of excitation source LEDs and sensors without filters for measuring fluorescence in fluorescein and green leaf extract

This paper presents the characterization of excitation source LEDs and sensors without filters for measuring fluorescence in fluorescein and green leaf extract. For this purpose, eight light-emitting diodes (LEDs) were used with the following characteristics: one blue, one green, one red, one infrared, and four violets. The first four LEDs were used as sensors without filters to detect fluorescence induced by the other four violet LEDs in 11 samples of different fluorescein concentrations and in 14 samples of different dilutions of green leaf extract. The results show that infrared LEDs can detect the red emission of green leaf extract and red and infrared LEDs detect the fluorescence of fluorescein in concentrations of up to 1.8 μM. The developed system allows and facilitates teaching optical spectroscopy in basic education without incurring high costs

A CMOS-based Lab-on-Chip Array for the Combined Magnetic Stimulation and Opto-Chemical Sensing of Neural Tissue

This paper presents a novel CMOS-based lab-on-chip platform for non-contact magnetic stimulation and recording of neural tissue. The proposed system is the first of its kind to integrate magnetic-stimulation and opto-chemical sensing in a single pixel, tesselated to form an 8 à 8 array. Fabricated in a commercially-available 0.35 ¿m CMOS technology, the system can be intrinsically used for both optical imaging and pH sensing and includes mechanisms for calibrating out sensor variation and mismatch. In addition to sensory acquisition via an integrated 10-bit ADC, a 64-instruction spatiotemporal pattern generator has been embedded within the array for driving the microscale magnetic neural stimulation. In this application the ISFET-based sensors are used to capacitively-couple neuronal charge in close proximity to the floating gate. Optical imaging hardware has also been embedded to provide topographic detail of the neural tissue.Published versio

Compact pixel architecture for CMOS lateral flow immunoassay readout systems

A novel pixel architecture for CMOS image sensors is presented. It uses only one amplifier for both integration of the photocurrent and in-pixel noise cancelation, thus minimizing power consumption. The circuit is specifically designed to be used in readout systems for lateral flow immunoassays. In addition a switching technique is introduced enabling the use of column correlated double sampling technique in capacitive transimpedance amplifier pixel architectures without the use of any memory cells. As a result the reset noise which is crucial in these architectures can be suppressed. The circuit has been designed in a 0.35-μm CMOS technology and simulations are presented to show its performance

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

Information Power Efficiency Tradeoffs in Mixed Signal CMOS Circuits

Increasingly sensors for biological applications are implemented using mixed signal CMOS technologies. As feature sizes in modern technologies decrease with each generation, the power supply voltage also decreases, but the intrinsic noise level increases or remains the same. The performance of any sensor is quantified by the weakest detectable signal, and noise limits the ability of a sensor to detect the signal. In order to explore the trade-offs among incoming signal, the intrinsic physical noise of the circuit, and the available power resources, we apply basic concepts from information theory to CMOS circuits. In this work the circuits are modeled as communication channels with additive colored Gaussian noise and the signal transfer characteristics and noise properties are used to determine the classical Shannon capacity of the system. The waterfilling algorithm is applied to these circuits to obtain the information rate and the bit energy is subsequently calculated. In this dissertation we restricted our attention to operational transconductance amplifiers, a basic building block for many circuits and sensors and oftentimes a major source of noise in a sensor system. It is shown that for typical amplifiers the maximum information rate occurs at bandwidths above the dominant pole of the amplifier where the intrinsic physical circuit noise is diminished, but at the same time the output signal is attenuated. Thus these techniques suggest a methodology for the optimal use of the amplifier, but in many cases it is not practical to use an amplifier in this manner, that is at frequencies above its 3dB cutoff. Further, a direct consequence of applying the classic waterfilling algorithm leads to the idea of using modulation techniques to optimize system performance by shifting signals internally to higher frequencies, providing a practical means to achieve the information rates predicted by waterfilling and at the same time maintaining the real world application of these amplifiers. In addition, the information rates and bit energy for basic CMOS amplifier configurations are studied and compared across configurations and processes. Further the additional design constraints formed by adding the information rate and the bit energy to traditional design characteristics is explored

CMOS SINGLE-PHOTON AVALANCHE DIODES AND MICROMACHINED OPTICAL FILTERS FOR INTEGRATED FLUORESCENCE SENSING

This dissertation presents a body of work that addresses the two most pressing challenges in the field of integrated fluorescence sensing, namely, the design of integrated optical sensors and the fabrication of high-rejection micro-scale optical filters. Two novel enabling technologies were introduced. They are: the perimeter-gated single-photon avalanche diode (PGSPAD), for on-chip photon counting, and the benzotriazole (BTA)-doped thin-film polymer filter, for on-chip ultraviolet light rejection. Experimental results revealed that the PGSPAD front-end, fabricated in a 0.5 μm standard mixed-signal CMOS process, had the capability of counting photons in the MHz regime. In addition, it was found that a perimeter gate, a structural feature used to suppress edge breakdown in the diode, also maximized the signal-to-noise-ratio in the high-count rate regime whereas it maximized sensitivity at low count rates. On the other hand, BTA-doped filters were demonstrated utilizing three commonly used polymers as hosts. The filters were patternable, utilizing the same procedures traditionally used to pattern the undoped polymer hosts, a key advantage for integration into microsystems. Filter performance was analyzed using a set of metrics developed for optoelectronic characterization of integrated fluorescence sensors; high rejection levels (nearing -40 dB) of UV light were observed in films of only 5 μm in thickness. Ultimately, BTA-doped filters were integrated into a portable sensor, and their use was demonstrated in two types of bioassays

Metal-Induced Fluorescence Quenching in Carbon Dots for Sensing Applications

Overexposure to metals can induce adverse health and environmental effects, thus monitoring metal concentrations is crucial. While current detection techniques are highly sensitive, they come at elevated costs, which limit their global use. As such, cheap and accessible sensors, providing both sensitivity and selectivity, are in high demand. With high surface area-to-volume ratios, tunable fluorescence and surface chemistries, nanoparticles are under investigation for development as metal sensors. However, many challenges exist including photobleaching, toxicity and a lack of selectivity. Owing to their low cytotoxicity, water-dispersibility and photostability, carbon dots have emerged as interesting alternatives. These amorphous carbon-based particles are ~10 nm in diameter and mainly composed of carbon, oxygen and hydrogen. While they have been investigated in metal sensing applications, the focus remains primarily on the application rather than the fundamental understanding of the mechanism of carbon dot-metal interactions in solution. In this work, we study the synthesis of carbon dots using several cheap and accessible precursors resulting in a surface decorated with functional groups such as amines, carboxylic acids and thiols. Following extensive purification protocols aimed at removing impurities that could bind to metal cations, we evaluate how these surface groups impact metal-carbon dot interactions. We demonstrate that some of our systems evidence sensitivity to Pb2+ and Hg2+ and exploit our knowledge of charge density and hard-and-soft acid-base theory to explain these findings and the underlying mechanism. This work provides a better understanding of metal-carbon dot interactions, which can allow us to design more sensitive and selective optical probes

INTEGRATION OF CMOS TECHNOLOGY INTO LAB-ON-CHIP SYSTEMS APPLIED TO THE DEVELOPMENT OF A BIOELECTRONIC NOSE

This work addresses the development of a lab-on-a-chip (LOC) system for olfactory sensing. The method of sensing employed is cell-based, utilizing living cells to sense stimuli that are otherwise not easily sensed using conventional transduction techniques. Cells have evolved over millions of years to be exquisitely sensitive to their environment, with certain types of cells producing electrical signals in response to stimuli. The core device that is introduced here is comprised of living olfactory sensory neurons (OSNs) on top of a complementary metal-oxide-semiconductor (CMOS) integrated circuit (IC). This hybrid bioelectronic approach to sensing leverages the sensitivity of OSNs with the electronic signal processing capability of modern ICs. Intimately combining electronics with biology presents a number of unique challenges to integration that arise from the disparate requirements of the two separate domains. Fundamentally the obstacles arise from the facts that electronic devices are designed to work in dry environments while biology requires not only a wet environment, but also one that is precisely controlled and non-toxic. Design and modeling of such heterogeneously integrated systems is complicated by the lack of tools that can address the multiple domains and techniques required for integration, namely IC design, fluidics, packaging, and microfabrication, and cell culture. There also arises the issue of how to handle the vast amount of data that can be generated by such systems, and specifically how to efficiently identify signals of interest and communicate them off-chip. The primary contributions of this work are the development of a new packaging scheme for integration of CMOS ICs into fluidic LOC systems, a methodology for cross-coupled multi-domain iterative modeling of heterogeneously integrated systems, demonstration of a proof-of-concept bioelectronic olfactory sensor, and a novel event-based technique to minimize the bandwidth required to communicate the information contained in bio-potential signals produced by dense arrays of electrically active cells

Temporal Noise Analysis And Measurements Of Cmos Active Pixel Sensor Operating In Time Domain

Image sensors in standard CMOS technology are increasing used for consumer, industrial and scientific applications due to their low cost, high level of integration and low power consumption. Further, image sensors in mainstream complementary metal-oxide-semiconductor (CMOS) technology are preferred because they are the lowest cost and easiest/fastest option to implement. For CMOS image sensors, a key issue is their noise behavior. Therefore, we have studied the noise characteristics of CMOS image sensors operating in time domain. Two important noise sources are the reset noise and integration noise. The reset noise is due to the reset in CMOS image sensors operating in voltage domain. The integration noise is that accumulated during light integration and was found to be the constant, independent of light intensity. Our circuit analysis shows that the signal-to-noise ratio (SNR) is also constant and independent of light intensity. 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