The development of a micro-scanner with real-time diagnostic capabilities

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A broad range of medical and industrial applications make use of miniature scanners. Dr Haijun Li and his colleagues from the University of Michigan have conducted ground-breaking research into molecular imaging in the digestive tract, developing and validating novel imaging systems for the early detection of disease. At the heart of the project is the development of a lightweight, compact scanner that can achieve extraordinarily large optical scan angles, capable of visualising a large region of diseased tissue in real time.

The development of optical imaging techniques that can deliver high-resolution images at high speeds is essential for the observation of cellular and molecular events in real time. New methods of optical imaging using multiple fluorescence channels simultaneously can significantly improve our ability to inspect epithelial cells for early detection of disease in internal organs, including the colon, oesophagus, lungs, pancreas, and stomach.

A multi-disciplinary team at the cutting edge of optical imaging diagnostics

Dr Haijun Li and his colleagues from the University of Michigan have conducted ground-breaking research on molecular imaging in the digestive tract, developing and validating novel imaging systems for the early detection of disease. Dr Li has been part of a cutting-edge translational research project that bridges engineering and medicine, advancing sub-cellular high resolution optical diagnostic methods for the investigation of disease within the native tissue microenvironment in living animals and human subjects. At the heart of the project is the development of a lightweight, compact scanner that can achieve extraordinarily large optical scan angles. This will allow practitioners to visualise cells and tissues over a large field of view in real time, enabling the early detection of cancer and other diseases.

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The design of Micro Electromechanical System (MEMS) devices

A broad range of medical and industrial applications make use of miniature scanners, whose internal mechanisms have traditionally enabled them to achieve deflection angles of several tens of degrees and translational movements of up to only a small fraction of a millimetre. Current technologies, however, require much greater angles of deflection and wider movements.

Micro Electromechanical System (MEMS) technology is commonly used to fabricate medical and industrial devices that can perform fast scanning with large angular deflections, low power consumption, and high mechanical reliability. Dr Li and his colleagues have pooled their skills and talents from different areas of expertise, ranging from physics and engineering to numerical modelling, to advance the development of a magnificent piece of miniature technology: a lightweight, compact scanner capable of achieving exceptionally large scan angles. Their system is based on a novel lever-based mechanism into a compact MEMS scanner, capable of achieving a full circumferential range with over a half millimetre of translational motion. This is a remarkable technological achievement, as the design and fabrication of high-speed MEMS scanners with wide deflection angles in a compact size is very challenging.

Improving range of motion while retaining optical image quality

Axial scanning is needed to collect optical sections of tissue in the vertical plane, the optimal direction for following the development of normal epithelium and monitoring invasion of disease. Standard optical components that move in this dimension are slow, and the images they collect are prone to movement artifacts. MEMS scanners are able to perform fast scanning with large axial displacements and translational motions. The design and fabrication of high-speed MEMS scanners with wide deflection angles require sophisticated optical technologies, such as larger mirror dimensions to capture more light, greater forces, and torques to achieve higher scan amplitudes at faster speeds.

MEMS-based methodologies have the potential for mass manufacture with low-cost batch fabrication. Current scanners are designed to achieve either large translational or rotational motion. However, few technologies can achieve large amplitudes in both modes. The system developed by Dr Li and his team consists of a mirror with millimetre dimensions, which is supported by two symmetric lever-based suspensions and belongs to a mechanism that allows movements to quickly shift from the translational to the rotational mode. A system of springs allows large deflection angles while providing resistance from lateral bending. Large vertical displacement motion and scan angles can be achieved by using long levers.

“MEMS scanners enable real-time fluorescence imaging, distinguishing between normally developed epithelium and transformed, diseased tissue.”

Fabrication of the scanner

The structure of the scanner is finalised by using a finite element model (FEM) to achieve stable rotational and translational motion and to minimise crosstalk from mechanical and electrical coupling. A CMOS-compatible silicon-on-insulation (SOI) micromachining process is used for the fabrication. Silicon dioxide layers, which are used as hard masks, are firstly deposited on double sides of the SOI wafer, and then patterned to define structures of the scanner. Deep-reactive ion-etching (DRIE) cuts away the exposed silicon in both of device and handle layers of SOI wafer for forming the electrostatically comb-driven actuators, the electrical pads, the electrical isolation trenches, and the reflectors. The buried silicon dioxide layer of SOI wafer is then removed with the help of buffered hydrofluoric acid (BHF), for releasing movable silicon structures and the remaining silicon dioxide layers on the wafer surfaces. Finally, a 60 nm layer of aluminium is deposited on the top silicon surface of the scanner and used as the reflective layer on the reflector and the electrical contact layer on the pads. The thickness is adequate to achieve a reflectivity that is greater than 85% over a wide range of wavelengths.

Fig. 1 Schematic. (A) A 1.5 mm diameter reflector is supported by two symmetric lever-based suspensions that are actuated by two rows of in-plane comb-drive actuators at resonance (top view). The suspensions form a compliant mechanism to convert motion between the (B) translational and (C) rotational modes (side view). (D) H-shaped torsional springs attached to the corners of the chip allow for large angular rotations while providing high resistance to lateral bending. (E) Multi-turn central-clamped folded-beam springs attach the reflector to the levers, and provide large deflection angles in the folding direction while resisting lateral bending. This spring is connected to the central axis of the reflector via a straight bar to achieve a high ratio for either torsion or translation of the reflector to torsion of the lever. Image Credit: https://www.osapublishing.org/oe/fulltext.cfm?uri=oe-27-11-16296&id=412890#articleFigures

To evaluate the quality of the reflector surface, a 635 nm laser beam is deflected to measure the optical scan angle. When this is assessed, only one edge of the substrate is mounted, to prevent the deflected beam from being obstructed when scanning in the torsional mode. A displacement sensor is used to measure the extent of the translational motion. The pattern generated by the reflected laser beam demonstrates a full circumferential (up to 494o) rotational scan angle, and a translational displacement of over half a millimetre. This design results in an ultra-large scan range in ambient pressure with little risk for mechanical fracture.

The device discussed above is an example of a resonant micro-mirror, a system where optical signals are manipulated on a very small size scale, using integrated mechanical and electrical forces. The motion of a resonant micro-mirror is based on parametric resonance, a phenomenon well understood in many areas of science, including the stability of ships or the forced motion of a swing. Parametric resonance occurs when the frequency drive applied to an oscillatory object is twice its natural frequency.

Concluding remarks and future directions

Dr Li and his multi-disciplinary team at the University of Michigan have developed a lightweight, compact scanner based on electrostatic actuation and parametric resonance that can achieve extraordinarily large optical scan angles and large out-of-plane translational displacements in excess of half a millimetre under ambient pressure.

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A very important application of MEMS micro-mirrors is the development of MEMS axial scanners, which represent one of the most advanced frontiers in medical imaging. In a review article published in 2017, Dr Li and his collaborators illustrate the example of a MEMS scanner that enables real-time fluorescence imaging of mouse colon epithelium, capable of distinguishing between normally developed epithelium and transformed, diseased tissue. By employing this type of scanner and a biaxial MEMS mirror, vertical cross-sectional imaging with a beam axial-scanning range of 200 µm and a frame rate of 5 to 10 Hz are enabled. Other applications of parametric resonance include optical switches, dynamic displays, laser micro-scanners, optical shutters, micro-spectrometers, and micro-lenses.

A limitation of the system is that it can only work in resonance, a property that limits the ability to acquire three-dimensional images. Furthermore, the system is sensitive to optical aberrations at large angles and displacements, and can affect image resolution. Further work is underway to optimise the structural design and modify the fabrication process to improve scanner performance. However, significant advantages over competing methods include fast scan speeds, rapid response times, low power consumption, and high mechanical reliability.


The development of this sophisticated imaging technology requires considerable technical expertise. Once made available, highly trained personnel are needed to support its maintenance. How soon do you foresee that your micro-scanner could be made widely available to clinicians and medical researchers?

Dr Li has patented the technologies, is currently commercialising these devices, and will make these micro-scanners widely available to clinicians and medical researchers for use in advanced imaging systems for early cancer detection in the next few years.

 

References

  • Li, H., Duan, X., Li, G., Oldham, K. and Wang, T. (2017). An Electrostatic MEMS Translational Scanner with Large Out-of-Plane Stroke for Remote Axial-Scanning in Multi-Photon Microscopy. Micromachines, [online] 8(5), p159. Available at: http://dx.doi.org/10.3390/mi8050159
  • Li, H., Oldham, K. and Wang, T. (2019). Three degree-of-freedom resonant scanner with full-circumferential range and large out-of-plane displacement. Optics Express 27, pp 16296-16307
DOI
10.26904/RF-137-1660181377

Research Objectives

Dr Haijun Li develops novel scanning mechanisms for molecular imaging in the digestive tract.

Funding

National Institutes of Health (NIH),
National Institute of Biomedical Imaging and Bioengineering (NIBIB),
Grant R01 EB020644

Collaborators

Kenn R Oldham, Thomas D Wang

Bio

Haijun Li received a Ph.D. in microelectronics and solid-state electronics from Jilin University (2007). He was a post-doc at Nanyang Technology University (2008-2011) and a Senior Engineer at the Hebei Semiconductor Research Institute (1997-2008). He is currently a Research Investigator at the University of Michigan, where he develops MEMS-based endomicroscopes.

Haijun Li

Contact
University of Michigan
109 Zina Pitcher Place, BSRB 1728, Ann Arbor
MI 48109-2200
USA

E: haijunl@umich.edu
T: +1 (734) 615 4834
W: https://sites.google.com/a/umich.edu/wang_lab

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