Integrated ultrasonic particle positioning and low excitation light fluorescence imaging

A compact hybrid system has been developed to position and detect fluorescent micro-particles by combining a Single Photon Avalanche Diode (SPAD) imager with an acoustic manipulator. The detector comprises a SPAD array, light-emitting diode (LED), lenses, and optical filters. The acoustic device is formed of multiple transducers surrounding an octagonal cavity. By stimulating pairs of transducers simultaneously, an acoustic landscape is created causing fluorescent micro-particles to agglomerate into lines. The fluorescent pattern is excited by a low power LED and detected by the SPAD imager. Our technique combines particle manipulation and visualization in a compact, low power, portable setup

Progress Towards a Multi-Modal Capsule Endoscopy Device Featuring Microultrasound Imaging

Current clinical standards for endoscopy in the gastrointestinal (GI) tract combine high definition optics and ultrasound imaging to view the lumen superficially and through its thickness. However, these instruments are limited to the length of an endoscope and the only clinically available, autonomous devices able to travel the full length of the GI tract easily offer only video capsule endoscopy (VCE). Our work seeks to overcome this limitation with a device (“Sonopill”) for multimodal capsule endoscopy, providing optical and microultrasound (μUS) imaging and supporting sensors1. μUS transducers have been developed with multiple piezoelectric materials operating across a range of centre frequencies to study viability in the GI tract. Because of the combined constraints of μUS imaging and the low power / heat tolerance of autonomous devices, a hybrid approach has been taken to the transducer design, with separate transmit and receive arrays allowing multiple manufacturing approaches to maximise system efficiency. To explore these approaches fully, prototype devices have been developed with PVDF, high-frequency PZT and PMN-PT composites, and piezoelectric micromachined ultrasonic transducer arrays. Test capsules have been developed using 3D printing to investigate issues including power consumption, heat generation / dissipation, acoustic coupling, signal strength and capsule integrity. Because of the high functional density of the electronics in our proposed system, application specific integrated circuits (ASICs) have been developed to realise the ultrasound transmit and receive circuitry along with white-light and autofluorescence imaging with single-photon avalanche detectors (SPADs). The ultrasound ASIC has been developed and the SPAD electronics and optical subsystem have been validated experimentally. The functionality of various transducer materials has been examined as a function of frequency and ultrasound transducers have been developed to operate at centre frequencies in the range 15 - 50 MHz. Ex vivo testing of porcine tissue has been performed, generating images of interest to the clinical community, demonstrating the viability of the Sonopill concept

A monolithic single-chip point-of-care platform for metabolomic prostate cancer detection

There is a global unmet need for rapid and cost-effective prognostic and diagnostic tools that can be used at the bedside or in the doctor's office to reduce the impact of serious disease. Many cancers are diagnosed late, leading to costly treatment and reduced life expectancy. With prostate cancer, the absence of a reliable test has inhibited the adoption of screening programs. We report a microelectronic point-of-care metabolite biomarker measurement platform and use it for prostate cancer detection. The platform, using an array of photodetectors configured to operate with targeted, multiplexed, colorimetric assays confined in monolithically integrated passive microfluidic channels, completes a combined assay of 4 metabolites in a drop of human plasma in under 2 min. A preliminary clinical study using L-amino acids, glutamate, choline, and sarcosine was used to train a cross-validated random forest algorithm. The system demonstrated sensitivity to prostate cancer of 94% with a specificity of 70% and an area under the curve of 0.78. The technology can implement many similar assay panels and hence has the potential to revolutionize low-cost, rapid, point-of-care testing

Photocurrent dependent response of a SPAD biased by a charge pump

A diagnostic pill is required to reach parts of the gastrointestinal tract that are inaccessible to endoscopes and detect the fluorescence from cancer cells. The key component of this pill is a very sensitive light detector that is compact enough to be integrated within the pill. In this paper, a charge pump is described that can bias a single photon avalanche detector as effectively as a bench top power supply

Design and implementation of a wireless capsule suitable for autofluorescence intensity detection in biological tissues

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

Wireless capsule for autofluorescence detection

Variations in tissue autofluorescence (AF) can be exploited to detect early signs of intestinal cancer, however current endoscopic AF systems are only able to inspect the oesophegus and large intestine. We present the design, fabrication and testing of a pill capable of inducing and detecting AF from mammalian intestinal tissue. The prototype comprises an application specific integrated circuit (ASIC), illumination LED, optical filters to minimize sensor response to crosstalk from the illumination wavelength, a pulse counter/control unit and a radio transmitter. The ASIC contains a single photon avalanche diode detector (SPAD), and integrate high voltage charge pump (up to 37.9 V) power supply. The SPAD operates above its breakdown voltage to operate in Geiger mode, and exhibits a detection efficiency peak at 465 nm, sufficiently close to human tissue autofluorescence's peak of 520±10 nm. The ASIC was fabricated using a commercial high-voltage CMOS process. The complete device uses only 21.4 mW

CMOS nanophotonic chemi-sensor with integrated readout system

This dataset includes simulation data, experimental data, images of the fabricated structures and all the data used to make the figures in the paper