FLOWCYTE Flow Cytometers introduced in 2006:

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FLOWCYTE Flow Cytometers introduced in
2006 Worlds first all fiber optic
collection/wavelength separation detection system
(DISPEC) yielding a new generation
instrument sensitivity, stability, flexibility,
size cost
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Fluorescence Nanotags for Flowcytometry Aggregatio
n-Enhanced Fluorescence and Two-Photon Absorption
in Nanoaggregate and Organically Modified Silica
Nanoparticles
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NANOCLINIC PLATFORMS FOR NANOMEDICINE
Silica and Organically Modified Nanoparticles
Pores for cellular communications
Therapeutic agents with Optical/PET/MRI imaging
agents
Surface Charge, reactive sites for addition of
targetting agents and binding of DNA/RNA
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Nanoclinic BioTechnology Magnetic Therapy

• Advantages
• Multimodal payloads for imaging and therapy
• Magnetocytolytic (therapy) using DC magnetic
  field
• MRI contrast agent
• Targeted delivery
• Real-time monitoring of efficacy

Magnetic Core
Optical Probe
Diagram of Targeted Magnetic Nanoclinic
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Nanoclinic Biotechnology Photodynamic Therapy
ORMOSIL Shell
HPPH

• Advantages
• Increased tumor uptake
• Targeting capability
• Enhanced efficacy
• Near IR photoactivation
• Multimodal imaging
• Real time monitoring of efficacy

TEM image of HPPH doped ORMOSIL nanoparticles
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Harvesting of two-photon excitation for near IR
photodynamic therapy to reach deeper tumor
Near IR excitation (TPA)
Collaboration with L-S. Tan(AFRL, Dayton),
J.M.J.Frechet (University of California,
Berkeley)
W.R. Dichtel, J. M. Serin, C.Edder, J.M. J.
Fréchet, M.Matuszewski, L.-S. Tan, T. Y.
Ohulchanskyy,. and P. N. Prasad, JACS 2004, 126,
5380.
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Harvesting of two-photon excitation energy for
PDT can be realized using a nanoparticle platform
Two-photon absorbing donor and singlet oxygen
generating acceptor co-encapsulated in the
ORMOSIL nanoparticles
Size lt 20 nm
T.Ohulchanskyy, D.Bharali, and P.N.Prasad,
unpublished
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Gene Therapy
Applications cancer, genetic disorders
(diabetes, cystic fibrosis, etc),
neurodegenerative, immunodeficiency disorders,
diabetes, microbial diseases, etc. Problems in
Gene Therapy Immunologic problems with viral
based systems Genetic material susceptible to
enviromental degradation No capability of
targeted delivery of genetic material
Nanoparticle Approaches Gene replacement
single gene defects, discrete cell
populations Suicide genes eliminate specific
cells or cell functions (i.e., cancer
cells) Protective genes express protective gene
product (i.e, viral/bacterial infections) Immune
stimulation stimulate host immune response
(i.e., DNA vaccines) Cell Marking for
autologous bone marrow transplant, cancer
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ORMOSIL Based Non-Viral Vector Gene Transfection
hn
hn
FRET
EthD-1
(intercalated into DNA)
HPPH
DNA
ORMOSIL (20 nm)
hn
Visualization cellular of uptake of GFP-DNA-EMA
ORMOSIL nanoparticles
In vitro GFP expression in cells after
transfection with DNA-ORMOSIL
In vivo GFP expression neurons in cells of mouse
brain
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Opportunities in Nanomedicine

• In vivo Bioimaging, Spectroscopy, and Optical
  Biopsy
• Nano-Biophotonic Probes
• Targeted Multiple Therapy
• Multiphoton Processes for Biotechnology
• Real-Time Monitoring of Drug Interactions

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Challenges in Nanomedicine

• Monodispersion of nanoparticles
• Control of size, shape and surface functionality
• Scalability for clinical applications
• Reproducibility (quality control issues)
• Specificity and efficiency of targeting systems
• Efficacy of therapeutic action
• Biocompatibility of nanoparticles
• (toxicity, biofouling, tissue distribution, and
  elimination)

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Introduction to Biophotonics Paras N.
Prasad (John Wiley Sons, 2003) SUMMARY OF
CONTENTS
1. Introduction 2. Fundamentals of Light and
Matter 3. Basics of Biology 4. Fundamentals of
Light-Matter Interactions 5. Principles of
Lasers, Current Laser Technology, and Nonlinear
Optics 6. Photobiology 7. Bioimaging Principles
and Techniques 8. Bioimaging Applications 9. Bios
ensors 10. Microarray Technology for Genomics and
Proteomics 11. Flow Cytometry 12. Light-Activated
Therapy Photodynamic Therapy 13. Tissue
Engineering with Light 14. Laser Tweezers and
Laser Scissors 15. Nanotechnology for
Biophotonics Bionanophotonics 16. Biomaterials
for Photonics
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Acknowledgements

• Researchers at the Institute
• Prof. E. Bergey
• Prof. K.-S. Lee
• Prof. M. Swihart
• Dr. Y. Sahoo
• Dr. H. Pudavar
• Dr. T. Ohulchanskyy
• Dr. A.Kachynskii
• Dr. A.Kuzmin
• Dr. D. Bharali
• Dr. D. Lucey
• Dr. S. Kim
• Dr. I. Roy
• Ms. H. Huang

• Outside Collaborators
• Prof. J M J Frechet
• Prof. M. Stachowiak
• Dr. A. Oseroff
• Dr. R. Pandey
• Dr. J. Morgan

• Support
• DURINT/AFSOR
• NSF
• NIH
• OISHEI FOUNDATION