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

Particle separation in surface acoustic wave microfluidic devices using reprogrammable, pseudo-standing waves

We report size and density/compressibility-based particle sorting using on-off quasi-standing waves based on the frequency difference between two ultrasonic transducers. The 13.3 MHz fundamental operating frequency of the surface acoustic wave microfluidic device allows the manipulation of particles on the micrometer scale. Experiments, validated by computational fluid dynamics, were carried out to demonstrate size-based sorting of 5–14.5 lm diameter polystyrene (PS) particles and density/compressibility-based sorting of 10 lm PS, iron-oxide, and poly(methyl methacrylate) particles, with densities ranging from 1.05 to 1.5 g/cm3 . The method shows a sorting efficiency of >90% and a purity of >80% for particle separation of 10 lm and 14.5 lm, demonstrating better performance than similar sorting methods recently published (72%–83% efficiency). The sorting technique demonstrates high selectivity separation of particles, with the smallest particle ratio being 1.33, compared to 2.5 in previous work. Density/compressibility-based sorting of polystyrene and iron-oxide particles showed an efficiency of 97 6 4% and a purity of 91 6 5%. By varying the sign of the acoustic excitation signal, continuous batch acoustic sorting of target particles to a desired outlet was demonstrated with good sorting stability against variations of the inflow rate

A highly compact packaging concept for ultrasound transducer arrays embedded in neurosurgical needles

State-of-the-art neurosurgery intervention relies heavily on information from tissue imaging taken at a pre-operative stage. However, the data retrieved prior to performing an opening in the patient’s skull may present inconsistencies with respect to the tissue position observed by the surgeon during intervention, due to both the pulsing vasculature and possible displacements of the brain. The consequent uncertainty of the actual tissue position during the insertion of surgical tools has resulted in great interest in real-time guidance techniques. Ultrasound guidance during neurosurgery is a promising method for imaging the tissue while inserting surgical tools, as it may provide high resolution images. Microfabrication techniques have enabled the miniaturisation of ultrasound arrays to fit needle gauges below 2 mm inner diameter. However, the integration of array transducers in surgical needles requires the development of advanced interconnection techniques that can provide an interface between the microscale array elements and the macroscale connectors to the driving electronics. This paper presents progress towards a novel packaging scheme that uses a thin flexible printed circuit board (PCB) wound inside a surgical needle. The flexible PCB is connected to a probe at the tip of the needle by means of magnetically aligned anisotropic conductive paste. This bonding technology offers higher compactness compared to conventional wire bonding, as the individual electrical connections are isolated from one another within the volume of the paste line, and applies a reduced thermal load compared to thermo-compression or eutectic packaging techniques. The reduction in the volume required for the interconnection allows for denser wiring of ultrasound probes within interventional tools. This allows the integration of arrays with higher element counts in confined packages, potentially enabling multi-modality imaging with Raman, OCT, and impediography. Promising experimental results and a prototype needle assembly are presented to demonstrate the viability of the proposed packaging scheme. The progress reported in this work are steps towards the production of fully-functional imaging-enabled needles that can be used as surgical guidance tools

Microfabrication of electrode patterns for high-frequency ultrasound transducer arrays

High-frequency ultrasound is needed for medical imaging with high spatial resolution. A key issue in the development of ultrasound imaging arrays to operate at high frequencies (⩾30 MHz) is the need for photolithographic patterning of array electrodes. To achieve this directly on 1–3 piezocomposite, the material requires not only planar, parallel, and smooth surfaces, but also an epoxy composite filler that is resistant to chemicals, heat, and vacuum. This paper reports, first, on the surface finishing of 1–3 piezocomposite materials by lapping and polishing. Excellent surface flatness has been obtained, with an average surface roughness of materials as low as 3 nm and step heights between ceramic/polymer of ∼80 nm. Subsequently, high-frequency array elements were patterned directly on top of these surfaces using a photolithography process. A 30-MHz linear array electrode pattern with 50-μm element pitch has been patterned on the lapped and polished surface of a high-frequency 1–3 piezocomposite. Excellent electrode edge definition and electrical contact to the composite were obtained. The composite has been lapped to a final thickness of ∼55 μm. Good adhesion of electrodes on the piezocomposite has been achieved and electrical impedance measurements have demonstrated their basic functionality. The array was then packaged, and acoustic pulse-echo measurements were performed. These results demonstrate that direct patterning of electrodes by photolithography on 1–3 piezocomposite is feasible for fabrication of high-frequency ultrasound arrays. Furthermore, this method is more conducive to mass production than other reported array fabrication techniques

Surface preparation of 1-3 piezocomposite material for microfabrication of high frequency transducer arrays

A key issue in the development of ultrasound imaging arrays to operate at frequencies above 30 MHz is the need for photolithographic patterning of array electrodes. To achieve this directly on a 1-3 piezocomposite requires planar, parallel and smooth surfaces. This paper reports an investigation of the surface finishing of 1-3 piezocomposite material by mechanical lapping and/polishing that has demonstrated that excellent surface flatness can be obtained. Subsequently, high frequency array elements have been fabricated on these surfaces using a low temperature lift-off photolithography process. A 50 MHz linear array with 30 pm element pitch has been patterned on the lapped and polished surface of a low frequency 1-3 piezocomposite. Good electrode edge definition and electrical contact to the composite were obtained. Additionally, patterning has been demonstrated on a fine-scale composite, itself suitable for operation above 30 MHz.</p

Hybridising Photonic and Biotechnologies to CMOS

Complementary metal oxide semiconductor (CMOS) technology lies at the heart of all computing and communications equipment, and has also been very successful as an image sensing technology, revolutionising digital imaging. New possibilities for CMOS are now being explored and delivered, including applications in gene sequencing, cell sorting, terahertz imaging and image fusion. We present recent data on the development of ion sensitive field effect transistors for large scale arrays used in gene sequencing and chemical imaging. These devices are capable of following proton ion evolution and diffusion sufficiently fast to be able to measure the ion dynamics in an aqueous medium. These dynamic capabilities are further exploited to demonstrate the measurement of enzyme kinetics on a CMOS chip. We also present advances in photonic technologies on CMOS and how they can be exploited for terahertz imaging and potential multispectral imaging on a chip. Finally, we present results on the development of single photon counting technology and its integration with acoustic particle sorting, presenting a future avenue for hand-held cell sorting and manipulation systems

Operation of a High Frequency Piezoelectric Ultrasound Array with an Application Specific Integrated Circuit

Integration of a piezoelectric high frequency ultrasound (HFUS) array with a microfabricated application specific integrated circuit (ASIC) performing a range of functions has several advantages for ultrasound imaging. The number of signal cables between the array/electronics and the data acquisition / imaging system can be reduced, cutting costs and increasing functionality. Electrical impedance matching is also simplified and the same approach can reduce overall system dimensions for applications such as endoscopic ultrasound. The work reported in this paper demonstrates early ASIC operation with a piezocomposite HFUS array operating at approximately 30 MHz. The array was tested in three different modes. Clear signals were seen in catch-mode, with an external transducer as a source of ultrasound, and in pitch-mode with the external transducer as a receiver. Pitch-catch mode was also tested successfully, using sequential excitation on three array elements, and viable signals were detected. However, these were relatively small and affected by interference from mixed-signal sources in the ASIC. Nevertheless, the functionality and compatibility of the two main components of an integrated HFUS - ASIC device have been demonstrated and the means of further optimization are evident