A disposable high numerical aperture microendoscope objective has been designed, fabricated, and tested for use with a fiber confocal reflectance microscope. The objective uses high precision LIGA fabricated components to integrate imaging components and hydraulic suction lines into a housing that measures only 3.85 mm in outer diameter and 14.65 mm in length. The hydraulics are used to translate tissue through the focal plane for three dimensional imaging. This device is diffraction limited for lambda = 850 nm, has a numerical aperture of 1.0, a field of view of 250 microm, and a working distance of 450 microm. The objective is intended for in vivo imaging of precancerous cells.

The most expensive aspects in producing high quality miniature optical systems are the component costs and long assembly process. A new approach for fabricating these systems that reduces both aspects through the implementation of self-aligning LIGA (German acronym for lithographie, galvanoformung, abformung, or x-ray lithography, electroplating, and molding) optomechanics with high volume plastic injection molded and off-the-shelf glass optics is presented. This zero alignment strategy has been incorporated into a miniature high numerical aperture (NA = 1.0W) microscope objective for a fiber confocal reflectance microscope. Tight alignment tolerances of less than 10 μm are maintained for all components that reside inside of a small 9 gauge diameter hypodermic tubing.A prototype system has been tested using the slanted edge modulation transfer function technique and demonstrated to have a Strehl ratio of 0.71. This universal technology is now being developed for smaller, needle-sized imaging systems and other portable point-of-care diagnostic instruments.

An integrated miniature multi-modal microscope (4M device) for microendoscopy was built and tested. Imaging performance is evaluated and imaging results are presented for both fluorescence and reflectance samples. Images of biological samples show successful imaging of both thin layers of fixed cells prepared on a slide as well as thick samples of excised fixed porcine epithelial tissue, thus demonstrating the potential for in vivo use.

The advanced requirements of bio-MEMS and MOEMS, i.e., low sidewall surface roughness, submicron critical dimension, and high aspect ratio, necessitate the use of an intermediate mask and a soft x-ray lithography process to fabricate working x-ray masks that are suitable for deep x-ray lithography. Intermediate masks consist of 2 to 2.5-m gold patterns on membranes/substrates that are highly transparent to x-ray radiation, whereas working masks possess greater than 5 m of gold patterns. In this work, 1-m silicon nitride membranes are produced by a low pressure chemical vapor deposition (LPCVD) process on both the front and backside of ͗100͘ prime grade wafers and anisotropic wet etch through silicon nitride etch masks. E-beam lithography is used to pattern 0.8-to 3-m-thick resist layers with submicron resolution. In the case of the 3-m resist layers, the features are electroplated with approximately 2 m of gold to form an intermediate mask. The 0.8-mthick layers are electroplated with gold up to a thickness of 0.6 m and form initial masks, which are in turn used in a soft x-ray lithographical process to make intermediate masks. The process of building a highresolution intermediate x-ray mask, directly by e-beam patterning a 3 m layer of e-beam resist, followed by gold electroplating, is found to be viable but requires the use of a high energy (Ͼ100 keV) e-beam writer. The stability of the resist pattern during soft x-ray lithography (SXRL) by use of an initial mask is found to be problematic. Double-side lithography and gold electroplating, can effectively reduce the aspect ratio of the mask pattern, eliminates the problems associated with the use of an initial mask to fabricate intermediate x-ray masks.

The multi-modal miniature microscope (4M) device to image morphology and cytochemistry in vivo is a microscope on a chip including optical, micro-mechanical, and electronic components. This paper describes all major system components: optical system, custom high speed CMOS detector and comb drive actuator. The hybrid sol-gel lenses, their fabrication and assembling technology, optical system parameters, and various operation modes (fluorescence, reflectance, structured illumination) are also discussed. A particularly interesting method is a structured illumination technique that delivers confocal-imaging capabilities and may be used for optical sectioning. For reconstruction of the sectioned layer a sine approximation algorithm is applied. Structured illumination is produced with LIGA fabricated actuator scanning in resonance. The spatial resolution of the system is 1 µm, and was magnified by 4x matching the CMOS pixel size of 4 µm (a lateral magnification is 4:1), and the extent of field of the system is 250µm. An overview of the 4M device is combined with the presentation of imaging results for epithelial cell phantoms with optical properties characteristic of normal and cancerous tissue labeled with nanoparticles.