Handheld subcellular-resolution single-fiber confocal microscope using high-reflectivity two-axis vertical combdrive silicon microscanner

Abstract

We introduce a handheld single-fiber laser-scanning confocal microscope, incorporating a high-reflectivity two-axis silicon vertical combdrive microscanner, aimed at in vivo early detection of epithelial precancers. The approach adopted is motivated by need for a portable, economical, biopsy-free, early precancer screening technology in low-infrastructure environments. Our microelectromechanical system (MEMS) based handheld probe integrates the microscanners with miniature objective lens system and flexible electrical routing in a forward-imaging configuration, with 4.8 mm distal probe tip outer diameter for unrestricted imaging access in biological sites such as the oral cavity and cervix. Reflectance confocal videos of a USAF 1951 resolution target and biological samples were obtained over 200 microm x 110 microm field of view, with 0.80 and 9.55 microm lateral and axial resolution, at 3.5-5.0 frames per second. With improvements to objective numerical aperture, our probe can enable precise evaluation of nuclear size, density, nucleus-to-cytoplasm ratio and cell density, which are important visual identifiers of epithelial precancers.

A review of fabrication processes for vertical comb drives

“…The custom double SOI wafer process (Kumar et al 2008;Lee et al 2004) is similar to the custom SOI wafer process, except it begins by patterning and DRIEing the outlines of the over-sized fixed comb teeth through the device layer of a standard SOI wafer. Silicon dioxide is then grown on a separate silicon wafer, and that wafer is fusion-bonded on top of the etched device layer.…”

“…Often vertical comb drives have torsion springs, while their fixed and movable comb pairs are positioned on either side of a mirror so that they may apply a force to one edge of the mirror or the other as voltage differences are applied between the combs of one pair at a time. Besides their obvious functions as micromotors and micropositioners (Selvakumar and Najafi 2003), the motion of vertical comb drives is often used to position micromirrors (Yeh et al 1999;Krishnamoorthy et al 2003;Hah et al 2003Hah et al , 2004Sasaki et al 2004;Tsai et al 2004;Carlen et al 2005;Lin et al 2005;Zhang et al 2005;Fang 2006, 2005;Selvakumar and Najafi 2003;Iwase et al 2008;Kim et al 2006aKim et al , 2009Ko et al 2006;Kumar et al 2008;Kumar and Zhang 2009) by lifting and/or tilting them in one or two axes. Actuating optical switches or scanners (Yeh et al 1999;Krishnamoorthy et al 2003;Hah et al 2003Hah et al , 2004Sasaki et al 2004;Tsai et al 2004;Carlen et al 2005;Lin et al 2005;Zhang et al 2005;Fang 2006, 2005;Selvakumar and Najafi 2003;Chung and Hsu 2008;Kim et al 2006aKim et al , 2009Ko et al 2006;Kumar et al 2008;Kumar and Zhang 2009), vertical comb drives can be used to obstruct a beam of light coming from optical fibres, or to steer a beam of light in a one-or two-dimensional space.…”

“…These abilities can be useful in applications such as laser printing, barcode reading, laser machining, and laser projection displays-as well as in optical communications networks (Hah et al 2003(Hah et al , 2004Carlen et al 2005;Wu and Fang 2006;Ko et al 2006;Kim et al 2009;Kumar and Zhang 2009). They can also be useful in portable confocal microscopes that can be used in vivo for early detection of cancers (Kumar et al 2008;Kumar and Zhang 2009), and for guided precision surgery (Kumar and Zhang 2009). Rotatable mirrors can also assist telescopes in tracking fastmoving light sources (Kim et al 2009).…”

CMOS-Compatible 2-Axis Self-Aligned Vertical Comb-Driven Micromirror for Large Field-of-View Microendoscopes

“…Fast-scanning micromirrors are an enabling technology for numerous applications including optical communication switching [1], display [2], and point-bypoint image acquisition systems [3][4][5]. Of particular interest is the ability to integrate such micromirrors into compact laser-scanning micro-endoscopes.…”

Handheld histology-equivalent sectioning laser-scanning confocal optical microscope for interventional imaging

“…The scaling laws in optics enable miniaturized imaging probes with functionality that cannot practically be achieved with traditional technologies (Solgaard 2008). Micromirrors powered by electrostatic vertical comb drives (Dooyoung et al 2004;Hyuck et al 2007;Krishnamoorthy et al 2003) provide the favorable optical characteristics, large deflection angles and fast response times required for real-time imaging, and have been employed in optical coherence tomography (Aguirre et al 2007;Woonggyu et al 2005;Kumar et al 2008a), confocal (Maitland et al 2006;Kumar et al 2008b) and multi-photon (Hoy et al 2008;Piyawattanametha et al 2006;Fu et al 2006) microscopies. Unfortunately, the micromirrors used in these studies have been fabricated by complicated micromachining processes, resulting in low wafer yield, non-linear transformation between input voltage and mechanical scan angle and unstable scanning characteristics due to a significant tendency to exhibit the pull-in phenomenon and cease scanning operation.…”