LLNL-PRES This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under contract DE-AC52-07NA Lawrence Livermore National Security, LLC Stavros G. Demos, Ph.D. Physicist, LLNL

Lawrence Livermore National Laboratory LLNL-PRES Autofluorescence Capturing UV Microscope Normal Esophagus Barrett’s Esophagus In vivo imaging of tissues microstructure Instantaneous diagnostic decision-making Non-invasive Reduces overall time spent in surgery Eliminates anxiety in waiting for diagnosis Reduces overall costs Greatly improves healthcare

Lawrence Livermore National Laboratory LLNL-PRES  Tissue sample is removed from the patient, sent to the lab, sliced into sections, mounted on slides, stained, and examined under microscope 1.Invasive 2.Results in multiple and repetitive surgeries 3.Imprecise 4.Random sampling error often misses pre-cancerous cells 5.Feedback takes extended amounts of time, (typically days) 6.Costs are extremely high 3 Source: murrasaca.com

Lawrence Livermore National Laboratory LLNL-PRES Endomicroscope systems  Instantaneous/real-time diagnostic info. for surgeon  Early, instant, accurate detection of disease (cancer, etc.)  Imaging helps guide surgical intervention 1.Noninvasive 2.Reduces repetitive surgeries 3.Precise cellular level images 4.Random sampling error is not a factor 5.Feedback is instantaneous 6.Drastically reduces overall costs 4 Source:

Lawrence Livermore National Laboratory LLNL-PRES Source: maunakeatech.com Mauna Kea’s Confocal Laser Endomicroscopy product: *optical sectioning *fluorescein

Lawrence Livermore National Laboratory LLNL-PRES

Lawrence Livermore National Laboratory LLNL-PRES  Visualization at the cellular level  Details of epithelial microstructure  Visualization of the margins  Targeted biopsies  High resolution images (spatial resolution ~ 1 µm) 7 Gold Standard: Tissue biopsy H&E Stain AF capturing UV Microscope: Real Time Epithelium of Stomach Features seen are comparable to Gold Standard, BUT AF capturing UV microscope provides greater speed, ease, & cost efficiency

Lawrence Livermore National Laboratory LLNL-PRES Heeryae.com Microscopy of the lumens of several organs Laparoscopic microscopy & Hand-held microscopy In vivo pathology markets Similar to frozen section biopsy without tissue processing, (all done in OR) Ex vivo market Visualization of cellular biochemistry & molecular function Cellular level view of drug delivery, targeting, cellular response, metabolism, and drug removal Pharmaceutical Industry In vivo study of tumors, tissue abnormalities, etc. Laboratory Animal Research In vivo lessons/study of the GI tract, organs, tissues, and cellular level features University and Secondary Bio/Anatomy Edu.

Lawrence Livermore National Laboratory LLNL-PRES  Available tabletop prototype  Tested microendoscope concept and design parameters (ex vivo)  Diagnostic studies: human esophageal tissues and animal tissues (ex vivo)  Animal imaging and stem cell localization/targeting Future Development: Proof of Principle in Humans (in vivo) 9 Source: businessinsider.com 1 Construct pre-product microendoscope 2 Validation using human subjects 3 Commercialization

Lawrence Livermore National Laboratory LLNL-PRES Genaro Mempin 10