Probability and Measure

In single-cell analysis, cellular activity and parameters are assayed on an individual, rather than population-average basis. Essential to observing the activity of these cells over time is the ability to trap, pattern and retain them, for which previous single-cell-patterning work has principally made use of mechanical methods. While successful as a long-term cell-patterning strategy, these devices remain essentially single use. Here we introduce a new method for the patterning of multiple spatially separated single particles and cells using high-frequency acoustic fields with one cell per acoustic well. We characterize and demonstrate patterning for both a range of particle sizes and the capture and patterning of cells, including human lymphocytes and red blood cells infected by the malarial parasite Plasmodium falciparum. This ability is made possible by a hitherto unexplored regime where the acoustic wavelength is on the same order as the cell dimensions.

/pdf/two-dimensional-single-cell-patterning-with-one-cell-per-4a4hbwbvtk.pdf

Two-dimensional single-cell patterning with one cell per well driven by surface acoustic waves

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Two Dimensional Signal And Image Processing

Flexible electronics has significantly advanced over the last few years, as devices and circuits from nanoscale structures to printed thin films have started to appear. Simultaneously, the demand for high-performance electronics has also increased because flexible and compact integrated circuits are needed to obtain fully flexible electronic systems. It is challenging to obtain flexible and compact integrated circuits as the silicon based CMOS electronics, which is currently the industry standard for high-performance, is planar and the brittle nature of silicon makes bendability difficult. For this reason, the ultra-thin chips from silicon is gaining interest. This review provides an in-depth analysis of various approaches for obtaining ultra-thin chips from rigid silicon wafer. The comprehensive study presented here includes analysis of ultra-thin chips properties such as the electrical, thermal, optical and mechanical properties, stress modelling, and packaging techniques. The underpinning advances in areas such as sensing, computing, data storage, and energy have been discussed along with several emerging applications (e.g., wearable systems, m-Health, smart cities and Internet of Things etc.) they will enable. This paper is targeted to the readers working in the field of integrated circuits on thin and bendable silicon; but it can be of broad interest to everyone working in the field of flexible electronics.

/pdf/ultra-thin-chips-for-high-performance-flexible-electronics-2vmyrzfqsj.pdf

Ultra-thin chips for high-performance flexible electronics

Single-photon avalanche diodes (SPADs) emerged as the most suitable photodetectors for both single-photon counting and photon-timing applications. Different complementary metal-oxide-semiconductor (CMOS) devices have been reported in the literature, with quite different performance and some excelling in just few of them, but often at different operating conditions. In order to provide proper criteria for performance assessment, we present some figures of merit (FoMs) able to summarize the typical SPAD performance (i.e., photon detection efficiency, dark counting rate, afterpulsing probability, hold-off time, and timing jitter) and to identify a proper metric for SPAD comparisons, when used either as single-pixel detectors or in imaging arrays. The ultimate goal is not to define a ranking list of best-in-class detectors, but to quantitatively help the end-user to state the overall performance of different SPADs in either photon-counting, timing, or imaging applications. We review many CMOS SPADs from different research groups and companies, we compute the proposed FoMs for all them and, eventually, we provide an insight on present CMOS SPAD technologies and future trends.

SPAD Figures of Merit for Photon-Counting, Photon-Timing, and Imaging Applications: A Review

An ultrasonic device for micro-patterning and precision manipulation of micrometre-scale particles is demonstrated. The device is formed using eight piezoelectric transducers shaped into an octagonal cavity. By exciting combinations of transducers simultaneously, with a controlled phase delay between them, different acoustic landscapes can be created, patterning micro-particles into lines, squares, and more complex shapes. When operated with all eight transducers the device can, with appropriate phase control, manipulate the two dimensional acoustic pressure gradient; it thus has the ability to position and translate a single tweezing zone to different locations on a surface in a precise and programmable manner.

https://pure.hw.ac.uk/ws/files/8156763/1.4802754.pdf

Interactive manipulation of microparticles in an octagonal sonotweezer

Fluorescence Imaging (FI) is a powerful technique in biological science and clinical medicine. Current FI devices that are used either for in-vivo or in-vitro studies are expensive, bulky and consume substantial power, confining the technique to laboratories and hospital examination rooms. Here we present a miniaturised wireless fluorescence endoscope capsule with low power consumption that will pave the way for future FI systems and applications. With enhanced sensitivity compared to existing technology we have demonstrated that the capsule can be successfully used to image tissue autofluorescence and targeted fluorescence via fluorophore labelling of tissues. The capsule incorporates a state-of-the-art complementary metal oxide semiconductor single photon avalanche detector imaging array, miniaturised optical isolation, wireless technology and low power design. When in use the capsule consumes only 30.9 mW, and deploys very low-level 468 nm illumination. The device has the potential to replace highly power-hungry intrusive optical fibre based endoscopes and to extend the range of clinical examination below the duodenum. To demonstrate the performance of our capsule, we imaged fluorescence phantoms incorporating principal tissue fluorophores (flavins) and absorbers (haemoglobin). We also demonstrated the utility of marker identification by imaging a 20 μM fluorescein isothiocyanate (FITC) labelling solution on mammalian tissue.

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Wireless fluorescence capsule for endoscopy using single photon-based detection.

Precision metabolomics and quantification for cost-effective rapid diagnosis of disease are the key goals in personalized medicine and point-of-care testing. At present, patients are subjected to multiple test procedures requiring large laboratory equipment. Microelectronics has already made modern computing and communications possible by integration of complex functions within a single chip. As More than Moore technology increases in importance, integrated circuits for densely patterned sensor chips have grown in significance. Here, we present a versatile single complementary metal–oxide–semiconductor chip forming a platform to address personalized needs through on-chip multimodal optical and electrochemical detection that will reduce the number of tests that patients must take. The chip integrates interleaved sensing subsystems for quadruple-mode colorimetric, chemiluminescent, surface plasmon resonance, and hydrogen ion measurements. These subsystems include a photodiode array and a single photon avalanche diode array with some elements functionalized to introduce a surface plasmon resonance mode. The chip also includes an array of ion sensitive field-effect transistors. The sensor arrays are distributed uniformly over an active area on the chip surface in a scalable and modular design. Bio-functionalization of the physical sensors yields a highly selective simultaneous multiple-assay platform in a disposable format. We demonstrate its versatile capabilities through quantified bio-assays performed on-chip for glucose, cholesterol, urea, and urate, each within their naturally occurring physiological range.

Multimodal Integrated Sensor Platform for Rapid Biomarker Detection

An all-digital interface, application specific integrated circuit (ASIC) has been developed for the control and data sampling of a quartz crystal microbalance (QCM)-based electronic nose. The ASIC is capable of measuring QCM resonant frequency between 0 and 11 MHz with a resolution of 1 Hz and ±1 Hz precision. The ASIC has been used to obtain measurements from polymer coated QCM sensors, in conjunction with polymer/carbon-black coated micro-resistance (μR) sensors, in the detection of primary alcohols. A full system-on-a-chip (SoC) electronic nose, currently under test, which supports arrays of eight QCM and eight μR sensors along with on-chip processing capability, is also described. © 2004 Elsevier B.V. All rights reserved.

/pdf/all-digital-interface-asic-for-a-qcm-based-electronic-nose-3fjess9sya.pdf

All-Digital Interface ASIC for a QCM-Based Electronic Nose

We report on the design, fabrication, testing, and packaging of a miniaturized system capable of detecting autofluorescence (AF) from mammalian intestinal tissue. The system comprises an application-specific integrated circuit (ASIC), light-emitting diode, optical filters, control unit, and radio transmitter. The ASIC contains a high-voltage charge pump and single-photon avalanche diode detector (SPAD). The charge pump biases the SPAD above its breakdown voltage to operate in Geiger mode. The SPAD offers a photon detection efficiency of 37% at 520 nm, which corresponds to the AF emission peak of the principle human intestinal fluorophore, flavin adenine dinucleotide. The ASIC was fabricated using a commercial triple-well high-voltage CMOS process. The complete device operates at 3 V and draws an average of 7.1 mA, enabling up to 23 h of continuous operation from two 165-mAh SR44 batteries.

James Beeley

Papers

Interactive manipulation of microparticles in an octagonal sonotweezer

Wireless fluorescence capsule for endoscopy using single photon-based detection.

Multimodal Integrated Sensor Platform for Rapid Biomarker Detection

All-Digital Interface ASIC for a QCM-Based Electronic Nose

Design and Implementation of a Wireless Capsule Suitable for Autofluorescence Intensity Detection in Biological Tissues