[PDF] - Biomedical Innovations by BioPOETS* Luke P. Lee Biomolecular PDF Document

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Luke P. Lee

Biomolecular Nanotechnology Center Berkeley Sensor & Actuator Center Department of Bioengineering

Biomedical Innovations by BioPOETS*

*BioPOETS: Biologically-inspired Photonics-Optofluidics-Electronics Technology & Science

UC Berkeley The BioPOETS

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)

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UC Berkeley The BioPOETS

Motivations
Biophotonics inspired by Nature
Biologically-inspired Optics
Biologically-inspired Fluidics
Biologically-inspired Electronics
Summary

http://biopoets.berkeley.edu

Outline

UC Berkeley The BioPOETS

Quantitative Biomedicine by BioPOETS*

*Biomolecular Photonics-Optofluidics-Electronics Technology & Science

Biologically Inspired Optical Systems Nanoplasmonic SERS for In-vitro Diagnostics Nanocrescent for In- vivo Molecular Probes Optofluidics for Biophotonic Controls Cellular BASICs: Biologic Application Specific Integrated Circuits

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UC Berkeley The BioPOETS

Quantitative Biomedical Science

[ ][ ] [ ] [ ]K

z x k t y z x k y x k t x ⋅ = ∂ ∂ ⋅ − = ∂ ∂ 3 2 2 1

Tissue Sample Empirical Analysis Kinetic Model Fitting Personalized Medicine

Fundamental Concepts:

Rapid collection of large experimental data sets
Intelligent consolidation of quantitative values

UC Berkeley The BioPOETS

Nano-Biophotonics Inspired by Nature

for Cellular Galaxy Biophysics and Imaging

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UC Berkeley The BioPOETS

Motivation:

Molecular Imaging

Time to Study the Inner Life: Cellular Galaxy!!

UC Berkeley The BioPOETS

From Telescope to Satellite Telescope

Galileo published Sidereus Nuncius in March 1610

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UC Berkeley The BioPOETS

Nanoring Nanotips

L a s e r E x c i t a t i

n

Surface-enhanced Raman scattering

Sharp edge (scattering “hot site”)

Nanocrescents:Nanosatellites

Nanoscale Biophotonic Receivers & Transmitters

Y. Lu, G. L. Liu, J. Kim, Y. Mejia, & L. P. Lee, Nano Letters, 5(1), 119-124 (2005).

Local Electromagnetic Field Enhancement Effect

UC Berkeley The BioPOETS

In-vivo Cellular Nanoscopy

Optical detection of electron transfer: in vivo for high spatial resolution nanoscopy.

Bionano Receivers & Transmitters 100 nm

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UC Berkeley The BioPOETS

SERS-based Nanocrescent’s LFE

600 800 1000 1200 1400 1600 100 200 300 400 500 1nM R6G 1μM R6G 10μM R6G 100μM R6G 1mM R6G Intensity [arb. unit] Raman Shift [cm

1]

615 788 1151 1347 1508 1545 1583 1659 1698 600 800 1000 1200 1400 1600 100 200 100nmO.D. Au nanobowl 60nm Au nanosphere 1698 1659 1583 1545 1508 1347 1151 788 615 Raman Shift [cm

1]

Intensity [arb. unit]

SERS spectra of different concentrations of R6G Comparison of SERS spectra from Au nano-crescent & nanospheres

Estimated LFE factor: ~ 3 Estimated LFE factor: ~ 3× ×10 102

2 Rhodamine 6G

High photostability
High quantum yield
Low cost

Excitation Excitation (785 nm) (785 nm)

1mM R6G

cf. Nanorings: LFE < 102

UC Berkeley The BioPOETS

Nanocrescent SERS Probes

Fe Ag Au L a s e r E x c i t a t i

n

S u r f a c e

e

n h a n c e d R a m a n S c a t t e r i n g Multilayered Nanocrescent SERS Hot Spots

Multiple particles with dispersed SERS hot spots

Multiple SERS Hot Spots

Single nanocrescent with multiple SERS hot spots

SERS Weak Spots

vs.

TEM image of nanocrescent (c)

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UC Berkeley The BioPOETS

1 μm 1 μm 1 μm 50 100 150 200 250 300 100 200 300 400 500 600 Pixel Intensity [a.u.] 50 100 150 200 250 300 100 200 300 400 500 600 Pixel Intensity [a.u.] 50 100 150 200 250 300 100 200 300 400 500 600 Pixel Intensity [a.u.] 1 μm 1 μm 1 μm 1 μm 1 μm 1 μm 50 100 150 200 250 300 100 200 300 400 500 600 Pixel Intensity [a.u.] 50 100 150 200 250 300 100 200 300 400 500 600 Pixel Intensity [a.u.] 50 100 150 200 250 300 100 200 300 400 500 600 Pixel Intensity [a.u.]

(b)

400 600 800 1000 1200 50 100 150 Intensity [a.u.] Raman Shift [cm

1]

background

blique excitation

perpendicular excitation Au MTMO 400 600 800 1000 1200 50 100 150 Intensity [a.u.] Raman Shift [cm

1]

background

blique excitation

perpendicular excitation Au Au MTMO

(c) (d)

500 600 700 800 900 1000 1100 1200 1300 150 200 250 300 350 Intensity [a.u.] Raman Shift [cm

1]

864 1030 637 N S N S N S N S 500 600 700 800 900 1000 1100 1200 1300 150 200 250 300 350 Intensity [a.u.] Raman Shift [cm

1]

864 1030 637 N S N S N S N S 50 100 150 200 250 300 350 5 10 15 20 25 30 35 40 45 Raman Peak Intensity at 637 cm

1

Rotation angle [degree] N S N S N S N S N S 50 100 150 200 250 300 350 5 10 15 20 25 30 35 40 45 Raman Peak Intensity at 637 cm

1

Rotation angle [degree] N S N S N S N S N S N S N S N S N S N S

(e) (f) (a)

Magnetic Nano- Crescent SERS

G. L. Liu, Y. Lu,
J. Kim, J. C. Doll,

and L. P. Lee

Advanced Materials (2005)

UC Berkeley The BioPOETS

Plasmonic Resonance Energy Transfer (PRET)

G. Liu, Y. Long, Y. Choi, T. Kang, and L. P. Lee (Nature Methods, 2007)

Nanospectroscopic Imaging

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UC Berkeley The BioPOETS

Time Resolved Dip Spectroscopy

Quantized Nanoplasmonic Dip Spectroscopy by PRET

Cyt C

UC Berkeley The BioPOETS

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UC Berkeley The BioPOETS

Molecular Dynamics of Cyt c

10 μm

Time resolved dip change

2μm UC Berkeley The BioPOETS

Multiplexed PRET for Functional Cellular Imaging

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Spatially Resolved in-vivo Cellular Imaging

Internalized GNPs Cytochrome c Mitochodrium Nucleus ER

0.5 1.0

Cyt c [c]

Mapping of Cellular Processing: Apoptosis Dynamics

PRET Nanospectroscopic Imaging

UC Berkeley The BioPOETS

Dynamic Molecular Ruler

for Measuring Nuclease Activity & DNA Footprinting

G. L. Liu et al. (Nature Nanotechnology, 2006)

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UC Berkeley The BioPOETS

Mechanism of Plasmon Resonance Wavelength Shift by Nucleolytic Reactions

1. Effective size change after DNA digestion. 2. Dielectric constant of dsDNA is dependent on its length (Langevin model). 3. Ionic condensation condition change due to the DNA length change

DNA length negative charges PR Shift

Au

s

*