James Beeley

Interactive manipulation of microparticles in an octagonal sonotweezer

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.

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.

Patterning of microspheres and microbubbles in an acoustic tweezers

We describe the construction of an ultrasonic device capable of micro-patterning a range of microscopic particles for bioengineering applications such as targeted drug delivery. The device is formed from seven ultrasonic transducers positioned around a heptagonal cavity. By exciting two or three transducers simultaneously, lines or hexagonal shapes can be formed with microspheres, emulsions and microbubbles. Furthermore, phase control of the transducers allows patterning at any desired position in a controlled manner. The paper discusses in detail direct positioning of functionalised microspheres, emulsions and microbubbles. With the advantages of miniaturization, rapid and simple fabrication, ultrasonic tweezers is a potentially useful tool in many biomedical applications.

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

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.

Acoustic Sensing and Ultrasonic Drug Delivery in Multimodal Theranostic Capsule Endoscopy

Video capsule endoscopy (VCE) is now a clinically accepted diagnostic modality in which miniaturized technology, an on-board power supply and wireless telemetry stand as technological foundations for other capsule endoscopy (CE) devices. However, VCE does not provide therapeutic functionality, and research towards therapeutic CE (TCE) has been limited. In this paper, a route towards viable TCE is proposed, based on multiple CE devices including important acoustic sensing and drug delivery components. In this approach, an initial multimodal diagnostic device with high-frequency quantitative microultrasound that complements video imaging allows surface and subsurface visualization and computer-assisted diagnosis. Using focused ultrasound (US) to mark sites of pathology with exogenous fluorescent agents permits follow-up with another device to provide therapy. This is based on an US-mediated targeted drug delivery system with fluorescence imaging guidance. An additional device may then be utilized for treatment verification and monitoring, exploiting the minimally invasive nature of CE. While such a theranostic patient pathway for gastrointestinal treatment is presently incomplete, the description in this paper of previous research and work under way to realize further components for the proposed pathway suggests it is feasible and provides a framework around which to structure further work.

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 singlephoton 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.

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.

Wide-range optical CMOS-based diagnostics

Colorimetric, chemiluminescence and refractive index based diagnostics are some of the most important sensing techniques in biomedical science and clinical medicine. Conventionally laboratories and medical clinics rely on bulky and dedicated equipment for each diagnostic technique independently. In this paper, we present CMOS sensor based solutions, comprising a single photon avalanche detector array and photodiode array. The CMOS platform offers low cost integration and wide range of light-based diagnostic techniques, leading to development of point-of-care devices.

Power management system for a capsule endoscope using autofluorescence imaging

Fluorescence endoscopy is one of the most effective methods for early cancer detection in the GI tract. An endoscopy pill that can provide qualitative and quantitative diagnostic information is required to inspect parts of the GI tract inaccessible to conventional endoscopes. A key component of this pill is an integrated high-sensitivity fluorescence imager with a high voltage source for biasing with very low power consumption. In this paper, we present a power management system for a high sensitivity imager to be integrated in a capsule endoscope for autofluorescence imaging.

Manipulation of microspheres and microbubbles in an octagonal sonotweezers

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.