Biomedical Innovations by BioPOETS* Luke P. Lee Biomolecular - PDF document

* BioPOETS : Bio logically-inspired P hotonics- O ptofluidics- E lectronics T echnology & S cience Biomedical Innovations by BioPOETS* Luke P. Lee Biomolecular Nanotechnology Center Berkeley Sensor & Actuator Center Department of Bioengineering The BioPOETS UC Berkeley Acknowledgments • Graduate & Post-doctoral Researchers : Dino Di Carlo (Harvard) Jeonggi Seo (PARC) Teawook Kang Gang Liu Paul Hung Yeonho Choi Jay Kim (Iowa State) Philip Lee Michelle Khine (UCM) Christy Trinkle (UK) Cristian Ionescu-Zanetti Adrian Lau Sunghoon Kwon (SNU) Nikolas Chronis (UM) Franklin Kim (NU) J. Tanner Nevill Poorya Sabounchi Kihun Jeong (KAIST) Yangku Choi (KAIST) Robert Szema Yitao Long (SWU) Megan Dueck Dukhyun Choi Yu Lu (Intel) David Breslauer Hansang Cho Eunice Lee Liz Wu Mimi Zhang Yolanda Zhang Ben Ross • Undergraduate Researchers Ryan Cooper Tao-yang Chen Brian Lee Selena Wong Todd Fong Andrea Fils Shalini Indrakanti Irene Sinn Angelee Kumar Albert Mach • Collaborators: Erin O’Shea @ Harvard Precision Biology @ Intel Wilhelm Krek @ ETH Zurich Lily Jan @ UCSF Yang Dan @ UCB Matthias Peter @ ETH Zurich Gabor Somorjai @ UCB Paul Alivisatos @ UCB Markus Stoffel @ ETH Zurich • Research Funding: NSF, DARPA, NASA, Intel Inc., Samsung Electronics, and CNMT(KMST) 1

The BioPOETS UC Berkeley Outline • Motivations • Biophotonics inspired by Nature • Biologically-inspired Optics • Biologically-inspired Fluidics • Biologically-inspired Electronics • Summary http://biopoets.berkeley.edu Quantitative Biomedicine by BioPOETS* The BioPOETS UC Berkeley * Biomolecular Photonics-Optofluidics-Electronics Technology & Science Nanocrescent for In- vivo Molecular Probes Biologically Inspired Optical Systems Optofluidics for Nanoplasmonic SERS Biophotonic Controls for In-vitro Diagnostics Cellular BASICs: Biologic Application Specific Integrated Circuits 2

The BioPOETS UC Berkeley Quantitative Biomedical Science ∂ x [ ][ ] [ ] = 2 − ⋅ k x y k x z ∂ 1 2 t ∂ [ ] K y = ⋅ k x z ∂ 3 t Tissue Kinetic Model Personalized Sample Empirical Analysis Fitting Medicine Fundamental Concepts: • Rapid collection of large experimental data sets • Intelligent consolidation of quantitative values The BioPOETS UC Berkeley Nano-Biophotonics Inspired by Nature for Cellular Galaxy Biophysics and Imaging 3

The BioPOETS UC Berkeley Motivation: Molecular Imaging Time to Study the Inner Life: Cellular Galaxy!! The BioPOETS UC Berkeley From Telescope to Satellite Telescope Galileo published Sidereus Nuncius in March 1610 4

The BioPOETS UC Berkeley Nanocrescents: Nanosatellites Nanoscale Biophotonic Receivers & Transmitters Nanoring Surface-enhanced Raman scattering Nanotips L Sharp edge E a x s c e i r t (scattering a t i o n “hot site”) Local Electromagnetic Field Enhancement Effect Y. Lu, G. L. Liu, J. Kim, Y. Mejia, & L. P. Lee, Nano Letters , 5(1), 119-124 (2005). The BioPOETS UC Berkeley In-vivo Cellular Nanoscopy 100 nm Bionano Receivers & Transmitters Optical detection of electron transfer: in vivo for high spatial resolution nanoscopy. 5

The BioPOETS UC Berkeley SERS-based Nanocrescent’s LFE SERS spectra of different concentrations of R6G Rhodamine 6G - High photostability 500 - High quantum yield 615 Excitation Excitation - Low cost 1151 1659 1583 788 1698 400 1545 (785 nm) (785 nm) 1508 Intensity [arb. unit] 1mM R6G 1347 300 100 μ M R6G 200 10 μ M R6G 100 1 μ M R6G 1nM R6G 0 600 800 1000 1200 1400 1600 -1 ] Raman Shift [cm Comparison of SERS spectra from Au nano-crescent & nanospheres 615 1mM R6G 100nmO.D. Au nanobowl Estimated LFE factor: ~ 3 × × 10 Estimated LFE factor: ~ 3 10 2 2 Intensity [arb. unit] 200 1151 1659 1583 788 1698 1545 1508 1347 cf. Nanorings: LFE < 10 2 100 60nm Au nanosphere 0 600 800 1000 1200 1400 1600 -1 ] Raman Shift [cm The BioPOETS UC Berkeley Nanocrescent SERS Probes Single Multiple particles nanocrescent with dispersed SERS with multiple hot spots SERS hot spots Multiple SERS SERS Hot Spots Hot Spots d e c g n n L a i a h e r s e n t r e a t E e - c x c S c a i f n t a u r a t S m i o a n R vs. SERS Weak Spots (c) Multilayered Nanocrescent Fe TEM image of Ag nanocrescent Au 6

The BioPOETS UC Berkeley (a) Magnetic Nano- Crescent (c) (b) background background 150 150 oblique excitation oblique excitation perpendicular excitation perpendicular excitation Intensity [a.u.] Intensity [a.u.] MTMO MTMO 100 100 1 μ m 1 μ m 1 μ m 1 μ m 1 μ m 1 μ m 1 μ m 1 μ m 1 μ m SERS Au Au Au 600 600 600 600 600 600 50 50 500 500 500 500 500 500 400 400 Intensity [a.u.] Intensity [a.u.] 400 400 Intensity [a.u.] Intensity [a.u.] 400 400 Intensity [a.u.] Intensity [a.u.] 300 300 300 300 300 300 200 200 200 200 200 200 0 0 100 100 100 100 100 100 0 0 0 0 0 0 0 0 50 50 100 100 150 150 200 200 250 250 300 300 0 0 50 50 100 100 150 150 200 200 250 250 300 300 0 0 50 50 100 100 150 150 200 200 250 250 300 300 400 400 600 600 800 800 1000 1000 1200 1200 Pixel Pixel Pixel Pixel Pixel Pixel -1 ] -1 ] Raman Shift [cm Raman Shift [cm G. L. Liu, Y. Lu, (e) 864 864 350 350 (d) 637 637 1030 1030 N N N N S S S S J. Kim, J. C. Doll, 300 300 Intensity [a.u.] Intensity [a.u.] 250 250 and L. P. Lee 200 200 N N N N S S S S 150 150 Advanced 500 500 600 600 700 700 800 800 900 1000 1100 1200 1300 900 1000 1100 1200 1300 Raman Shift [cm Raman Shift [cm -1 ] -1 ] Materials 45 45 (f) -1 -1 S S S N N N Raman Peak Intensity at 637 cm Raman Peak Intensity at 637 cm 40 40 N N N S S S (2005) 35 35 30 30 25 25 20 20 15 15 10 10 5 5 S S S N N N S S S S S S N N N N N N 0 0 0 0 50 50 100 100 150 150 200 200 250 250 300 300 350 350 Rotation angle [degree] Rotation angle [degree] The BioPOETS UC Berkeley Plasmonic Resonance Energy Transfer (PRET) Nanospectroscopic Imaging G. Liu, Y. Long, Y. Choi, T. Kang, and L. P. Lee ( Nature Methods, 2007 ) 7

The BioPOETS UC Berkeley Quantized Nanoplasmonic Dip Spectroscopy by PRET Cyt C Cyt C Time Resolved Dip Spectroscopy The BioPOETS UC Berkeley 8

The BioPOETS UC Berkeley Molecular Dynamics of Cyt c 10 μ m Time resolved dip change 2 μ m The BioPOETS UC Berkeley Multiplexed PRET for Functional Cellular Imaging 9

The BioPOETS UC Berkeley PRET Nanospectroscopic Imaging Spatially Resolved in-vivo Cellular Imaging Mapping of Cellular Processing: Apoptosis Dynamics Cytochrome c Mitochodrium Nucleus ER Internalized GNPs Cyt c [c] 1.0 0.5 0 The BioPOETS UC Berkeley Dynamic Molecular Ruler for Measuring Nuclease Activity & DNA Footprinting G. L. Liu et al. ( Nature Nanotechnology, 2006) 10