Micro-opto-mechanical pressure sensors (MOMPS) based on integrated optical Mach-Zehnder interferometers (MZI) have been fabricated at IMEC, exhibiting much improved sensitivity and noise performance compared to their piezoelectric and capacitive counterparts. However, the design of next generation MOMPS systems on chip still remains uncertain due to the intrinsic multiphysics nature covering mechanical, optical and electrical phenomena. For this reason, we present a sophisticated, flexible and customizable algorithmic tool for the multiphysics simulation and design of highperformance MOMPS systems on chip, including mechanical and optical effects as well as the electronic circuitry for the readout. Furthermore, static and dynamic operating regimes are analyzed, also comparing analytical solutions with experimental results and demonstrating a good agreement. Finally, system noise contributions generated by the optoelectronic components and readout electronics are calculated and a static sensitivity of 8 mV/Pa is measured in the fabricated sensors.
Metastasis is responsible for as many as 90% of cancer-related deaths, and the deadliest skin cancer, melanoma, has a high propensity for metastasis. Since hematogenous spread of circulating tumor cells (CTCs) is cancer’s main route of metastasis, detecting and destroying CTCs can impede metastasis and improve patients’ prognoses. Extensive studies employing exogenous agents to detect tumor-specific biomarkers and guide therapeutics to CTCs have achieved promising results, but biosafety remains a critical concern. Taking another approach, physical detection and destruction of CTCs is a safer way to evaluate and reduce metastasis risks. Melanoma cells strongly express melanosomes, providing a striking absorption contrast with the blood background in the red to near-infrared spectrum. Exploiting this intrinsic optical absorption contrast of circulating melanoma cells, we coupled dual-wavelength photoacoustic flow cytography with a nanosecond-pulsed laser killing mechanism that specifically targets melanoma CTCs. We have successfully achieved in vivo label-free imaging of rare single CTCs and CTC clusters in mice. Further, the photoacoustic signal from a CTC immediately hardware-triggers a lethal pinpoint laser irradiation that lyses it on the spot in a thermally confined manner. Our technology can facilitate early inhibition of metastasis by clearing circulating tumor cells from vasculature.
KEYWORDS: Ultrasonography, Transducers, 3D image processing, Photoacoustic imaging, 3D acquisition, 3D image reconstruction, Data acquisition, Signal detection, Silicon, Imaging systems
This paper reports the development of a new two-axis micromechanical scanning transducer for handheld 3D ultrasound imaging. It consists of a miniaturized single-element ultrasound transducer driven by a unique 2-axis liquid-immersible electromagnetic microactuator. With a mechanical scanning frequency of 19.532 Hz and an ultrasound pulse repetition rate of 5 kHz, the scanning transducer was scanned along 60 concentric paths with 256 detection points on each to simulate a physical 2D ultrasound transducer array of 60 × 256 elements. Using the scanning transducer, 3D pulse-echo ultrasound imaging of two silicon discs immersed in water as the imaging target was successfully conducted. The lateral resolution of the 3D ultrasound image was further improved with the synthetic aperture focusing technique (SAFT). The new two-axis micromechanical scanning transducer doesn’t require complex and expensive multi-channel data acquisition (DAQ) electronics. Therefore, it could provide a new approach to achieve compact and low-cost 3D ultrasound and photoacoustic imaging systems, especially for handheld operations.
Fast scanning is highly desired for both ultrasound and photoacoustic microscopic imaging. Limited by water environment required for acoustic propagation, traditional mircoelectromechanical system (MEMS) scanning mirrors could not be widely used. In this paper, a new water-immersible scanning mirror microsystem has been designed, fabricated and tested. Polymer hinges were employed to achieve reliable under water performance. Two pairs of high strength neodymium magnet disc and three compact RF choke inductor were used to actuate mirror module. Experimental results show that the fast axis can reach a mechanical scanning angle of ±15° at the resonance frequency of 350 Hz in air, and ±12.5° at the resonance frequency of 240 Hz in water, respectively. The slow axis can reach a mechanical scanning angle of ±15° at the resonance frequency of 20 Hz in air, and ±12.5° at the resonance frequency of 13 Hz in water, respectively. The two scanning axes have very different resonance frequencies, which are suitable for raster scanning.
Micro scanning mirrors that can operate reliably under water is useful in both ultrasound and photoacoustic microscopic imaging, where fast scanning of focused high-frequency ultrasound beams is desired for pixel-by-pixel data acquisition. This paper reports the development of a new micro-fabricated water-immersible scanning mirror with a small form factor. It consists of an optically and acoustically reflective mirror plate, which is supported onto two flexible polymer hinges and driven by an integrated electromagnetic micro-actuator. It can achieve one-axis scanning of ±12.1° at a resonant frequency of 250Hz in air and 210Hz in water, respectively. By optimizing the design and enhancing the fabrication with high-precision optical 3D printing, the overall size of the scanning mirror module is less than 7 mm × 5 mm × 7 mm. The small form factor, large scanning angle, and high resonant frequency of the new water-immersible scanning mirror make it suitable for building compact handheld imaging probes for in-vivo high-speed and wide-field ultrasound and photoacoustic microscopy.
Microscanning mirrors that can operate reliably under water are useful in both ultrasound and photoacoustic microscopic imaging, where fast scanning of focused high-frequency ultrasound beams is desired for pixel-by-pixel data acquisition. We report the development of a new microfabricated water-immersible scanning mirror with a small form factor. It consists of an optically and acoustically reflective mirror plate which is supported by two flexible polymer hinges and driven by an integrated electromagnetic microactuator. It can achieve 1-axis scanning of ±12.1 deg at a resonant frequency of 250 Hz in air and 210 Hz in water, respectively. By optimizing the design and enhancing the fabrication with high-precision optical three-dimensional printing, the overall size of the scanning mirror module is less than 7 mm×5 mm×7 mm. The small form factor, large scanning angle, and high-resonant frequency of the new water-immersible scanning mirror make it suitable for building compact handheld imaging probes for in vivo high-speed and wide-field ultrasound and photoacoustic microscopy.
Despite its critical function in coordinating the egress of inflammatory and immune cells out of tissues and maintaining fluid balance, the causative role of lymphatic network dysfunction in pathological settings is still understudied. Engineered-animal models and better noninvasive high spatial-temporal resolution imaging techniques in both preclinical and clinical studies will help to improve our understanding of different lymphatic-related pathologic disorders. Our aim was to take advantage of our newly optimized noninvasive wide-field fast-scanning photoacoustic (PA) microcopy system to coordinately image the lymphatic vasculature and its flow dynamics, while maintaining high resolution and detection sensitivity. Here, by combining the optical-resolution PA microscopy with a fast-scanning water-immersible microelectromechanical system scanning mirror, we have imaged the lymph dynamics over a large field-of-view, with high spatial resolution and advanced detection sensitivity. Depending on the application, lymphatic vessels (LV) were spectrally or temporally differentiated from blood vessels. Validation experiments were performed on phantoms and in vivo to identify the LV. Lymphatic flow dynamics in nonpathological and pathological conditions were also visualized. These results indicate that our newly developed PA microscopy is a promising tool for lymphatic-related biological research.
For both ultrasound and photoacoustic microscopic imaging, a fast scanning ability is required, whereas the liquid
environment for acoustic propagation limits the usage of traditional MEMS scanning mirrors. In this paper, a new waterimmersible
scanning mirror microsystem has been designed, fabricated and tested. To achieve reliable underwater
scanning, flexible polymer torsion hinges fabricated by laser micromachining were used to support the reflective silicon
mirror plate. Two efficient electromagnetic microactuators consisting of compact RF choke inductors and high-strength
neodymium magnet disc were constructed to drive the silicon mirror plate around a fast axis and a slow axis,
respectively. The performance of the water-immersible scanning mirror microsystem in both air and water were tested
using the laser tracing method. For the fast axis, the resonance frequency reached 224 Hz in air and 164 Hz in water,
respectively. The scanning angles in air and water under ±10 V AC driving (at the resonance frequencies) were ±13.6°
and ±10°. The scanning angles in both air and water under ±16 V DC driving were ±12°. For the slow axis, the resonance
frequency reached 55 Hz in air and 38 Hz in water, respectively. The scanning angles in air and water under ±10 V AC
driving (at the resonance frequencies) were ±8.5° and ±6°. The scanning angles in both air and water under ±10 V DC
driving were ± 6.5°. The feasibility of using such a water-immersible scanning mirror microsystem for scanning
ultrasound microscopic (SAM) imaging has been demonstrated with a 25-MHz ultrasound pulse/echo system and a
target consisting of three optical fibers.
By offering images with high spatial resolution and unique optical absorption contrast, optical-resolution photoacoustic
microscopy (OR-PAM) has gained increasing attention in biomedical research. Recent developments in OR-PAM have
improved its imaging speed, but have sacrificed either the detection sensitivity or field of view or both. We have
developed a wide-field fast-scanning OR-PAM by using a water-immersible MEMS scanning mirror (MEMS-ORPAM).
Made of silicon with a gold coating, the MEMS mirror plate can reflect both optical and acoustic beams. Because
it uses an electromagnetic driving force, the whole MEMS scanning system can be submerged in water. In MEMS-ORPAM,
the optical and acoustic beams are confocally configured and simultaneously steered, which ensures uniform
detection sensitivity. A B-scan imaging speed as high as 400 Hz can be achieved over a 3 mm scanning range. A
diffraction-limited lateral resolution of 2.4 μm in water and a maximum imaging depth of 1.1 mm in soft tissue have
been experimentally determined. Using the system, we imaged the flow dynamics of both red blood cells and carbon
particles in a mouse ear in vivo. By using Evans blue dye as the contrast agent, we also imaged the flow dynamics of
lymphatic vessels in a mouse tail in vivo. The results show that MEMS-OR-PAM could be a powerful tool for studying
highly dynamic and time-sensitive biological phenomena.
By offering images with high spatial resolution and unique optical absorption contrast, optical-resolution photoacoustic microscopy (OR-PAM) has gained increasing attention in biomedical research. Recent developments in OR-PAM have improved its imaging speed, but have to sacrifice either the detection sensitivity or field of view or both. We have developed a wide-field fast-scanning OR-PAM by using a water-immersible microelectromechanical systems (MEMS) scanning mirror (MEMS-OR-PAM). In MEMS-OR-PAM, the optical and acoustic beams are confocally configured and simultaneously steered, which ensures the uniform detection sensitivity. A B-scan imaging speed as high as 400 Hz can be achieved over a 3 mm scanning range. Using the system, we imaged the flow dynamics of both red blood cells and carbon particles in a mouse ear in vivo. Presented results show that MEMS-OR-PAM could be a powerful tool for studying highly dynamic and time-sensitive biological phenomena.
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