Dr. Richard Cote of Sylvester Comprehensive Cancer Center presented "New Technologies That Will Have an Impact on Cancer" at the 2011 WellBeingWell Conference in Miami.

1. New Technologies That Will Have an Impact on Cancer Sylvester Comprehensive Cancer Center Well-Being Session, April 26, 2011 Richard J. Cote, MD, FRCPath Chair, Pathology Director, Biomedical Nanoscience Institute University of Miami

2. Length Scales FITC IgG DNA Diameter GFP Virus Colloidal gold Bacterium Animal Cell Plant Cell 0.5nm 5nm 2nm 1nm 50nm 100nm 1  m 10  m 100  m Nanoworld Microworld

7. PSA Detection with Bionanosensor In 2 O 3 NW Device SWNT Mat Device

8. Challenge in Building and Using Nanosensor Devices: Need microfluidics 24 Sensor Array for Coupling with Microfluidic Delivery + = A sensor array chip with 3 rows of 8 devices is overlaid with a matching PDMS microflidic system . Indium Oxide Nanowires are grown chemically to lie across electrical ‘ source ’ and ‘ drain ’ to create a ‘ device ’. An FET array contains 3 rows of 8 devices to form a Sensor Array Chip.

11. Bone Marrow Occult Metastasis

14. Mean (and range) of sizes of normal cellular components of blood, and certain cancer cell lines. Universal Platform for Cell Capture Based on Size Normal blood components Cancer cell lines 0 5 10 15 20 25 30 Platelets RBC Basophils Lymphocytes Neutrophils Eosinophils Monocytes NCI-H522 J82 RT4 HCC-70 MDA-MB-231 HT1080 T24 SK-Br-3 HCC-38 LnCaP NCI-1395 Cell size ( μ m)

15. Microfilter Based Cell Separation Assembled Filter Device Parylene Filter Membrane SEM of Cell Captured on filter Syringe 1 PDMS Chamber Parylene Membrane Filter Trapped Tumor Cell RBC’s in the flow through MNCs 100µm A B C 100µm

16. Multiplexed Imaging On-Chip Multiplex PCR Her2/neu FISH analysis on microfilter CK PSA CK PSA DAPI

19. Serial CTC counts predict survival in prostate cancer Moreno et al Proc Am Soc Clin Oncol 2007;25:239s. DeBono et al, CCR , 2008, MSKCC, CCF, U Mich Kaplan–Meier plot for overall survival of CTC counts categories conversion at any time point following the early or late cycle of treatment. Survival times were calculated from the date of baseline (BL) CTC blood draw. Multivariate analysis was carried out using a Cox regression model with a time-dependant co-variable. 1 2 3 4 Curve Logrank Comparison p-Value* 1 vs. 2 0.1528 1 vs. 3 <0.0001 1 vs. 4 <0.0001 2 vs. 3 <0.0001 2 vs. 4 <0.0001 3 vs. 4 0.5013 %Probability of Survival Time from Baseline Blood Draw (Months) 0 2 4 6 8 10 12 14 16 18 22 24 26 28 30 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 20 *p-values not adjusted for multiple hypothesis tests Grp Description N (%) Median OS in months (95% CI) 1 <5 CTC at all draws 88 (38%) >26 (21.4 to -----) 2 > 5 CTC at BL & <5 CTC at last draw 45 (20%) 21.3 (18.4 to ----) 3 <5 CTC at Early Draw & > 5 CTC at Last Draw 26 (11%) 9.3 (8.2 to 11.3) 4 > 5 CTC at All Draws 71 (31%) 6.8 (5.8 to 10.3)

21. Nanoparticles can serve as imaging contrast agents Magnetized nanoparticles can be used to image sentinel lymph nodes Example: SentiMag technology by Endomagnetics Johnson L et al, Discov Med. 2010 Apr;9(47):374-9. QD800- based imaging agents tested in vivo are stable up to several days Yang et al, Oral Oncology, 46, 864-868, 2010

22. Cote et al J Clin Oncol. 1991 Recurrence Rates Based on Tumor Burden in the Bone Marrow

24. Nanosensor Platforms Team Nanosensor Collaborators Dr. Mark Thompson, USC Dr. Chong wu Zhou, USC Dr. Thomas Thundat, ORNL Dr. Ram Datar, UM Dr. Marco Curreli, USC Dr. Fumi Ishikawa, USC Dr. Henry Lin, ORNL Dr. Arun Majumdar

25. Dr. Yu Chong Tai, Caltech Dr. Ram Datar, UM Dr. Marija Balic, Austria Dr. Siyang Zheng , PennState Dr. Henry Lin, ORNL Anthony Williams, UM CTC Microfilter Team CTC Microfilter Collaborators