Design and Fabrication of Optomechanical Formalin Fixation Monitoring Systems Integrated with a Millifluidic Device

Abstract

Engineering design is a multi-step process and becoming more challenging when it comes to a translational system that requires new information framework for interdisciplinary fields such as medicine. The translational research is initiated from identifying a clinical niche and followed by conceptual design, simulation, prototyping, preliminary experiments, evaluation, and future design suggestion. In this dissertation, two independent projects for the design and development processes of translational opto-mechanical systems are presented to suggest a feasible medical device design, which can benefit clinical workflow and performance. The first project (Chapter 2, 3, and 4) is to develop a tissue quality monitoring system for an automated millifluidic system for pathology and the development cycle includes design, fabrication, testing, and evaluation of the systems. In our lab, a novel automated millifluidic system for cancer diagnosis using core needle biopsy (CNB) was under development to overcome the clinical needs in the conventional tissue preparation which are time and labor consuming. The millifluidic system for CNB will automate tissue preparation and imaging processes more rapidly and reliably with all-in-channel millifluidic flowing and non-contact monitoring systems. Especially, the formalin fixation step that is the most time consuming but less known tissue preparation step should be well assessed. The three primary aims are presented for this first project. The first aim was to design a low-cost but efficient SW elastography device for the CNB submerged in a millifluidic chamber, which simulates the process for the automated CNB microfluidic device. We choose the low-cost and less complicated laser speckle imaging (LSI) technique for SW visualization and velocity measurement, and the SW-LSI system consisting of a 532nm laser, a piezo-actuator and a camera was constructed for this study. The stiffness changes of phantoms and chicken breast tissues during formalin fixation are investigated for different sizes of the samples. We present the distinct temporal change of the tissue’s mechanical property by formalin fixation, where the plateau of the fixation level is shown within the time range of optimal fixation time in histopathology. The second aim was to evaluate the optical property of CNB by formalin fixation over time. This study was originated from the speculation of the prior study, where the visualization of CNB was greatly altered during formalin fixation. We performed a preliminary study of optical attenuation measurement for CNB using a broadband light source and spectroscopy. The relative optical attenuation changes of gelatin-based tissue phantom and various porcine tissues were evaluated. The optical attenuation data in broadband spectrum demonstrated different effects of fixation for various tissues. The third aim was to fabricate the 3D printed prototype of the optical attenuation monitoring station. For an effective unsophisticated configuration, a pair of laser diode and photodiode was employed. The single wavelength at 808nm was selected to enhance the mean optical path length to avoid blood-specific changes during formalin fixation. Both fused deposition modeling and stereolithography were used to fabricate the optical station framework and other optical components were embedded. The testing and calibration were conducted, and the pilot experiments were performed with porcine breast tissue to verify the feasibility of the proposed approach. The second project (Chapter 5) was to establish the product design framework for release of a novel photo-sensitive medical tape. Medical tape removal process is painful and causes medical adhesive-related skin injury (MARSI). We have introduced a photothermal sensitive medical tape by which an easy and painless tape removal is allowed while the initial strong adhesion provides a critical device securement. The prototype system consisting of off-the-shelf components was previously fabricated. This chapter focused on the analyses of preliminary testing and thermal performance data. The feasibility of the new medical tape system was evaluated with heat transfer simulation, and the design parameters for the future clinical system were proposed. In summary, two different projects of opto-mechanical device design and development are presented. For formalin fixation monitoring for the novel millifluidic system, the preliminary feasibility studies lead to the robust design and development of the SW-LSI system (Project 1-Aim1) and optical transmittance monitoring system (Project 1-Aim 2) for CNB formalin fixation. The 3D printed optical station fabricated (Project 1-Aim 3) demonstrates the product-level practicability of the CNB quality monitoring feature, which can potentially reduce the turn-around time from taking a biopsy to making a diagnosis, and to standardize the fixation and tissue handling processes in pathology workflow. The separate product design study (Project 2) of the photosensitive high adhesion medical tape suggests clinically practical design of the system, which considers potential users, use environments, and safety issues in addition to opto-mechanical operating parameters.