Raoul Kopelman

Our group includes students of analytical chemistry, physical chemistry, chemical biology, materials, applied physics, all interested in nanosystems and nanoexplorer devices. The problems range from the theoretical, such as stochastic formalisms and supercomputer simulations related to the patterns of reaction fronts in capillaries, to the applied, such as the development of biochemical nano-sensors, energy transducer supermolecules (artificial photosynthetic antenna), and in-vivo chemical measurements in brain cells, in collaboration with researchers from Neurotoxicology and the Medical School. The most recent work involves in-vivo chemical imaging.

In-Vivo Chemical Imaging – What is it? It is 5-dimensional imaging, spatially resolved, time resolved and chemically resolved, i.e., including the concentration of a given chemical analyte at each point in space and time. Obviously, we may focus on more than one analyte. When pertaining to in vivo imaging in an animal or human, it is assumed to be non-invasive and harmless. Notably, all the wonderful medical diagnostics developed over the last century, i.e., CT (X-ray), MRI, US (ultrasound), are for physical/structural imaging On the other hand, chemical tests in medicine are still done on ex vivo  samples, such as Blood, urine or biopsies, utilizing fairly “primitive” methods of chemical analysis. Moreover the obtained results retain little or no spatio-temporal information. What we still need is spatially resolved chemical information in real time. Why do we need such information? One example concerns cancer. It has long been known that tumors may be hypoxic, i.e. lower in oxygen than normal tissue. Such hypoxia, especially deep in the tumor, will suppress the effectiveness of any radiation therapy. Similarly, tumors may exhibit acidosis, i.e. low pH. This will suppress the effectiveness of many chemotherapeutic cancer drugs. Finally, it has been recently discovered that hyperkalemia, i.e. highly elevated concentrations of potassium ions in the extracellular medium, will suppress immunotherapy, the most promising modern cancer treatment. Thus, if we could map out the tumor distributions of oxygen, pH and K+ for a new cancer patient, it might help the caregivers decide early on what would be the most optimal course of treatment for this patient, the aim of what is called “personalized medicine”.

To achieve chemical imaging we use photo-acoustic imaging methods, which combine optical micro-spectroscopy with ultrasound detection, in combination with nanoparticle contrast agents. The later “nano-sonophores” are infra-red (IR) optical nanosensors (see below) that are targeted at cancer cells, which happens shortly after intravenous injection. The tunable IR laser photons get absorbed by these sensors, whose spectrum is characteristic of the analyte concentration. The absorbed photons create heat, which causes thermo-elastic expansion, resulting in ultrasound which easily penetrates the tissue and is recorded. The IR laser photons can penetrate about 1 cm, thus reach the subsurface tumor. Notably, with fiber-optic lasers, in most cases no more than 1 cm tissue penetration would be required.

An example of such a chemical image of a tumor, mapping the pH tissue distribution in real time, is given in our 2017 publications Nature Communications and Analytical Chemistry.

Other recent research includes novel molecular nano-explorer devices for the early detection and therapy of cancer. It also involves a novel cell-magnetorotation method enabling fast and sensitive detection of biopolymers, as well as ultra-rapid drug sensitivity tests on bacteria and cancer stem cells.

Our lab has produced the world's smallest light sources, voltmeters, viscosimeters and the smallest and fastest chemical sensors. This enables optical, spectral and chemical imaging on a nanometer scale. Novel fiber-optic and nano-sphere sensors (for pH, calcium, zinc, potassium, sodium, chloride, nitrite, nitric oxide, glucose and oxygen) reduce the sample volume and detection limit a billion-fold, and simultaneously the response time by a factor of a thousand. These sensors have been used to monitor biological processes, e.g., organogenesis in live rat-embryos, as well as pathogenic processes due to chemical pollution or poisons. Investigations are also performed on the primary chemical processes inside single neuron and cancer cells. Our recent molecularly targeted in-vivo nano-devices detect (with MRI) and kill (photo-dynamically) tumor cells, as well as heart arrhythmia causing cells.

The group has successfully produced some of the smallest non-trivial molecular architectures with directed energy transport (excitonics). An example is the dendrimer "nanostar" molecule with 39 phenyl-acetylene repeat units and a perylenic pendant. This is a new approach to molecular electronics and molecular optics, with applications to photosynthesis, biochemical nano-sensors, and nanotechnology. We have also made integrated organic light-source/sensor mini-arrays.

Our research on reaction nano-fronts has established important links between fractal and heterogeneous reaction kinetics. Experiments include reactions on enzymatic and industrial catalysts, micro-capillaries and porous membranes and materials. These new insights also enable us to study the local morphology in systems such as membranes, polymeric blends, thin crystalline films and catalytic surface islands, as well as intracellular biochemical reactions. Computer simulations and stochastic theories accompany the experimental work.

Awards

Etter Memorial Lecture in Materials Chemistry, University of Minnesota

Pittsburgh Analytical Chemistry Award, 2010
Richard Smalley Distinguished University Professorship of Chemistry, Physics and Applied Physics, 2006
ACS Division of Analytical Chemistry Award in Spectrochemical Analysis, 2005
American Chemical Society Morley Award    
American Physical Society Lady Davis Fellowship    
Fellow of the American Association for the Advancement of Science    
Guggenheim Fellow    
J. William Fulbright Research Award    
National Institutes of Health National Research Service Award    
National Science Foundation Creativity Award

Collegiate Inventors Grand Prize (together with Ph.D student, Jeff Anker), 2002

Representative Publications

In Vivo Quantitative Imaging of Tumor pH by Nanosonophore Assisted Multispectral Photoacoustic Imaging, Jo J, Lee C, Kopelman R, Wang X, Nature Communications 8: 471 (2017)

Ion-selective Nanosensor for Photoacoustic and Fluorescence Imaging of Potassium, Chang H. Lee, Jeff Folz, Wuliang Zhang, Janggun Jo, Joel Tan, Xueding Wang, Raoul Kopelman, Analytical Chemistry (2017) 89, 7943−7949 PMCID: PMC5799881, NIHMSID: NIHMS935460

Nanoparticle PEBBLE Sensors in Live Cells and In Vivo, Y.E.L. Koo, R. Smith, and R. Kopelman, Annual Review of Analytical Chemistry Volume 2, edited by E. Yeung and R. Zare, pp. 57-76, (2009). [Invited Review] PMCID: PMC2809032

Reaction Kinetics: Catalysis without a Catalyst, R. Kopelman, Nature Chemistry, Invited View Article, [Invited] 2, 430-431 (2010).

Experimental System for One-Dimensional Rotational Brownian Motion, B. H. McNaughton, P. Kinnunen, M. Shlomi, C. Cionca, S.N. Pei, R. Clarke, P. Argyrakis, R. Kopelman, Shaul Mukamel Festschrift special issue, J. Physical Chemistry B 115 pp.5212-5218 (2011).

Methylene Blue-Conjugated Hydrogel Nanoparticles and Tumor-Cell Targeted Photodynamic Therapy, H.J. Hah, G. Kim, Y.E.K. Lee, D.A. Orringer, O. Sagher, M.A. Philbert, R. Kopelman, Macromolecular Bio Science 11, p. 90-99, (2011).

Optochemical Nanosensors, Y.E.L. Koo. and R. Kopelman, Handbook of Nanophysics, Edited by K.D. Sattler , Taylor & Francis Group, 33-1-33-16, (2011).

Asynchronous Magnetic Bead Rotation (AMBR) biosensor in microfluidic droplets for rapid bacterial growth and susceptibility measurements. I. Sinn, P. Kinnunen, T. Albertson, B.H. McNaughton, D.W. Newton, M.A. Burns, R. Kopelman, Lab on a Chip, 11 (15), 2604 - 2611 (2011).

Targeted blue nanoparticles as photoacoustic contrast agent for brain tumor delineation, A. Ray, X. Wang, Y.E. Koo Lee, H.J. Hah, G. Kim, T. Chen, D. Orringer, O. Sagher, X. Liu, R. Kopelman, Nano Research 4(11): 1163?1173, (2011).

Nanoparticle Induced Cell Magneto-Rotation: Monitoring Morphology, Stress and Drug Sensitivity of a Suspended Single Cancer Cell, R. Elbez, B.H. McNaughton, L. Patel, K.J. Pienta, R. Kopelman, PLoS ONE 6(12): doi:10.1371/journal.pone.0028475, pp. 1-11, (2011). PMCID: 3236752.

Targeted, Multifuncional Hydrogel Nanoparticles for Imaging and Treatment of Cancer, R. Kopelman and Y.E.K. Lee, Chapter in "Multifunctional Nanoparticles for Drug Delivery Applications", Springer, Editor: Sonke Svenson, ch. 11, p.225-255 (2012).

Hydrogel Nanoparticles with Covalently Linked Coomassie Blue for Brain Tumor Delineation Visible to the Surgeon?s Eyes, G. Nie, H.J. Hah, G. Kim, Y.E. Koo Lee, M. Qin, T. Ratani, P. Fotiadis, A. Miller, A. Kochi, D. Gao, T. Chen, D. Orringer, O. Sagher, M. Philbert, R. Kopelman, Small, 8(6):884-91 (2012). doi: 0.1002/smll.201101607

Self-assembled Magnetic Bead Biosensor for Measuring Bacterial Growth and Antimicrobial Susceptibility Testing, P. Kinnunen, B. H. McNaughton, T. Albertson, I. Sinn, S. Mofakham, D. Newton, A. Hunt and R. Kopelman, Small (2012) DOI: 10.1002/smll.201200110, PMID: 22674520.

A Novel Nonionic, Multi-Surfactant System and Separation Method for the Synthesis of Active Carbonic Anhydrase Nanoparticles, G. Nie, D. Si, G. Kim, Z. Shi, T. Ratani, Y.E. Koo Lee, C. Fierke , R. Kopelman, Advanced Mat. Res. Vols., 399-401 pp 509-513 (2012).

Asynchronous magnetic bead rotation (AMBR) micro-viscometer for rapid, sensitive and label-free studies of bacterial growth and drug sensitivity, I. Sinn, T. Albertson, P. Kinnunen, D.N. Breslauer, B.H. McNaughton, M.A. Burns, R. Kopelman, Analytical Chemistry (2012) PMID: 22507307, PMC3381929.

Two-photon fluorescence imaging super-enhanced by multi-shell nanophotonic particles, with application to subcellular pH, A. Ray , Y.E. Koo Lee , G. Kim, R. Kopelman, Small, 8(14): 2213?2221, (2012).

Nanoparticle PEBBLE Sensors in Live Cells, editor: Michael Conn, Y.E.K. Lee and R. Kopelman; Imaging and Spectroscopic Analysis of Living Cells MIE (Methods in Enzymology), UK: Academic Press, Vol. 504, Chapter 21, pp. 419-470 (2012).

Checking Out the Insides of Cells, Y.E.K. Lee and R. Kopelman. Nanobiotechnology. 7, 148-149 (2012).

Asynchronous Magnetic Bead Rotation Microviscometer for Rapid, Sensitive, and Label-Free Studies of Bacterial Growth and Drug Sensitivity, I. Sinn, T. Albertson, P. Kinnunen, D. Breslauer, B. McNaughton, M. Burns, R. Kopelman, Analytical Chemistry, DOI: 10.1021/ac300128p, NIHMS382689, (2012).

Research Areas(s)

• Analytical Chemistry
• Bioanalytical Chemistry
• Biophysical Chemistry
• Chemical Biology
• Materials Chemistry
• Nano Chemistry
• Optics and Imaging
• Physical Chemistry
• Sensor Science
• Laser Spectroscopy and Imaging
• Chemical and Biochemical Nano-Sensors
• Molecular Optics
• Fractal and Micro-domain Reaction Kinetics