Digital Holography and BioInterferometry: Biodynamic Imaging
Edward M. Purcell Distinguished Professor of Physics
Professor Nolte is the Edward M. Purcell Distinguished Professor of Physics. Edward Mills Purcell (1912 - 1997) received his undergraduate BS from Purdue University in 1933 where he was encouraged by Prof. Lark-Horowitz to do undergraduate research in physics under Profs. Walerstein and Yearian. Purcell was awarded the 1952 Nobel Prize in Physics for his discovery of nuclear magnetic resonance, the physical basis of MRI imaging. In 1977 he published a landmark paper "Life at Low Reynolds Number" that applied principles of hydrodynamics to biological systems. He was awarded, with Howard Berg, the Max Delbrück Prize for biophysics of the American Physical Society in 1984. He made a lasting mark on physics education with his relativistic approach to teaching electricity and magnetism in his 1965 Berkeley Physics Course textbook.
Purcell, E. M. (1977). "Life at low Reynolds number". American Journal of Physics 45: 3–11.
Animated Dynamics (AniDyn) Inc.
Prof. Nolte is a technical founder, with John Turek of Basic Medical Sciences, of Animated Dynamics (AniDyn) Inc. that is commercializing Biodynamic Imaging for Early Drug Discovery and Biomedical applications. AniDyn is seeking academic collaborators interested in exploring effects of drugs on live tissues. Students interested in company internships also can apply. Please contact Prof. D. Nolte at firstname.lastname@example.org.
In the News
Sept 1, 2015
NSF Phase-II SBIR Awarded
Prof. Nolte's biotechnology start-up company, Animated Dynamics Inc., has been awarded a two-year Phase-II SBIR (Small Business Innovative Research) award from NSF to develop a Biodynamic Microscope product.
May 1, 2015
Mira Award: Indiana Technology Innovation of the Year
Animated Dynamics Inc. receives the Mira Award for Indiana Technology Innovation of the Year.
June 1, 2013
NIH R01 Grant Awarded
Purdue University, through Prof. Nolte laboratory, has been awarded an NIH R01 four-year award to study the use of Biodynamic Imaging in the selection of cancer chemotherapy in ovarian cancer. Initial studies will focus on animal models and will transition to a pilot clinical trial in human patients in 2016.
May 1, 2013
Purdue Discovery Park Fellow
Prof. David Nolte has been chosen to be a Discovery Park Fellow with joint affiliation to Bindley Bioscience Center and the Oncological Sciences Center. The project is to pursue BioDynamic Imaging across a wide range of disciplines as diverse as cancer therapy, drug discovery and development, reproductive science, developmental biology, liver and kidney disease, biomechanics and microrheology, tissue engineering, cell cycle signaling, and plant science and agriculture.
February 19, 2013
• Press Release: Animated Dynamics LLC
Animated Dynamics won first place in the 26th Burton D. Morgan Business Plan Competition. Biodynamic Imaging is a new technique that images the activity of living tissue to assesses its state of health. Applications include discovery of new anticancer drugs, selection of therapy for personalized cancer care and viability assessment for in vitro fertilization. Biodynamic Imaging measures intracellular motion through laser light scattering. Award image
November 30, 2012
• Press Release: Fellow of AAAS
David Nolte has been elected a Fellow of the American Association for the Advancement of Science (AAAS) Section on Physics• Optics and Photonics News Article
Tissue dynamics Spectroscopy (TDS) uses biointerferometry to provide unique spectrogram fingerprints for the response of living tissue to applied drugs.
March 6, 2007
Holographic images use shimmer to show cellular response to anticancer drug
The response of tumors to anticancer drugs has been observed in real-time 3-D images using technology developed at Purdue University. (SPIE Newsroom)
October 17, 2005
David D. Nolte was the winner of the 2005 Herbert Newby McCoy Award
The Herbert Newby McCoy Award is Purdue University's highest award for outstanding contributions to science.
| McCoy Distinguished Lecture (PDF)
May 18, 2004
BioCDs could hit No. 1 on doctors' charts
While-you-wait medical tests that screen patients for thousands of disease markers could be possible with compact-disk technology patented by Purdue University scientists. The future of diagnostic blood tests may lie in your computer's CD drive -- if a Purdue scientist can carry out his vision.
May 7, 2002
Lasers light way to 3-D imaging in Purdue lab
Purdue University scientists developing a new imaging technology have created the world's first "visual fly-throughs" of a living tumor.
Prof. Nolte is a technical founder of Quadraspec, Inc., now Perfinity Biosciences, located at the Purdue Research Park, that is sub-licensing the BioCD to Antech Diagnostics with products for diagnostic testing using label-free highly sensitive assays with high content.
The Digital Holography and BioInterferometry group, directed by Professor David D. Nolte, applies the sensitivity of laser interferometry to a broad range of topics that include solid state physics, plasmonics in gold films, graphene, semiconductor physics, biointerferometry in biological physics, protein surface chemistry and holographic imaging of living biological tissues. In all thes areas, the picometer sensitivity of laser interferometry provides unprecidented sensitivity to study the optical properties of materials. For example, the BioCD (Biological Compact Disk) relies on diffraction of lasers from antibodies on spinning discs.
The physics of partial coherence, combined with the propagation of light through biological tissues, has lead to the development of Biodynamic Imaging which measures intracellular motions in living tissue. This is a new form of biomedical imaging contrast which is used to explore the physics of biodynamics and biomechanics. Potential applications are in the field of cancer therapeutics and artificial reproductive technology (ART). More than 60% of chemotherapy patients gain no benefit from first-line cancer drugs, yet all suffer from the adverse side effects of chemotherapy, degrading quality of life. Biodynamic Imaging can select better drugs that are personalized to the patient, increasing positive outcomes for cancer patients and improving quality of life for them and their families. Biodynamic Imaging is also a candidate technology for embryo viability assessment in IVF applications. Because of its general sensitivity to intracellular motion, Biodynamic Imaging is also a general new tool for screening applications in drug discovery and development. To this end, we have launched a new biotech start-up company Animated Dynamics Inc. that is working to bring these promises to the clinic.
Research positions are open for graduate research assistantships (RAs) and for undergraduates pursuing a senior thesis. Experimental research focuses on the interaction of light and lasers with living biological systems. Theoretical research focuses on photon Monte-Carlo approaches to coherent light propagation in random dynamic media.
Textbook on Modern Dynamics (Oxford University Press, 2015)
By David D. Nolte (Oxford University Press, 2015)
Topics: Trajectories, Geodesics, Hamiltonian Physics, Chaos, Evolutionary Dynamics, Synchronization, Dynamic Networks, Neural Networks, Economic Dynamics, Differential Geometry, Special Relativity, General Relativity
Expanded Problems and Corrections can be found at www.works.bepress/ddnolte
Textbook on BioInterferometry (Springer, Fall 2011)
Optical Interferometry for Biology and Medicine, by David D. Nolte (Springer, 2011)
Topics: Interferometers, Speckle, Holography, Optical Coherence Tomography, Biosensors, BioCD, Cellular Dynamics, Dynamic Light Scattering, Interference Microscopy, Nanoparticles, Motility Contrast Imaging, Tissue Dynamics Spectroscopy. Table of Contents (PDF)Link to Amazon.com
Popular Book on Optical Technologies at the turn of the (new) Century (Simon&Schuster, Fall 2001)
Mind at Light Speed: A New Kind of Intellegence, by David D. Nolte (Simon&Schuster, 2001)
Topics: The Glass Bead Game, Machines of Light, Visual Communication, Telecom, Quantum Information and Quantum Computing.Link to AbeBooks.com
Holographic Biodynamic Imaging
Volumetric imaging of cellular motion in a tumor spheroid. Full size
Laser fields propagating through scattering tissue retain an exponentially decaying coherence that can write holographic gratings on a holographic medium. The first volumetric holograms of living tissue were made by the Adaptive Optics and Biophotonics group at Purdue University in 2002 using ultra-sensitive dynamic holographic film called photorefractive quantum well (PRQW) devices. Digital holography, using CCD cameras, provides similar advantages for holographic optical coherence imaging (OCI). In biomedical imaging applications, intracellular motility, recorded as shimmering holograms, acts as a novel imaging contrast agent. Recent interest is on the action of anti-mitotic cancer drugs on tissue. | Cellular motility as a novel contrast agent in digital holography of tissue
The recent development of Tissue Dynamics Spectroscopy (TDS) opens up new opportunities to study the functional influence of new drug compounds on living tissue. Tissue Dynamics Spectroscopy performs label-free non-invasive measurements of the intracellular dynamics inside living tissue and evaluates how these dynamics are altered by applied drugs. The need that TDS addresses is its ability to bridge the gap that has persisted in the drug-discovery pipeline between high-throughput 2D monolayer cultures and preclinical animal models (where drug failures are much more expensive). Three-dimensional tissue-based drug screens (for therapeutic efficacy and specificity) are needed to bridge this gap because 3D tissues are more representative of cellular and tissue responses to applied drugs than those in 2D monolayer culture. Currently there are no volumetric imaging modalities that capture drug response without labels deep in tissue far from surface effects. The response of tissue to an applied drug is represented as a drug-response spectrogram. Every different type of drug has a different spectrogram fingerprint. Different spectrogram features are related to different mechanisms of action of the drug, for instance monitoring cell metabolism or cytoskeletal integrity, or apoptotic response.
The stage in early drug discovery that comes after high-throughput screening is called “hit confirmation and expansion”. At this stage in the drug development pipeline, screens are needed to test “hits” for therapeutic efficacy (does it modify a selected target?) and specificity (does it only affect a selected target?). Target response is either molecular (pathway) or physiological (phenotypic profile). Tissue dynamics spectroscopy enters the marketplace as a new screening technology for early drug discovery. The field of use of TDS is hit confirmation and expansion. The target is high-content phenotypic profiling of physiological response to drug candidates.
Fig. Drug Response Spectrograms for phenotypic profiling of Iodoacetate and Cytochalasin D
A nanometer-high protein spot on a silicon disc measured using molecular interferometry. Full size
The BioCD performs molecular diagnostics in the form of a compact disc. The BioCD, invented in the Adaptive Optics and Biophotonics group at Purdue University, combines the simplicity of spinning-disc interferometry (SDI) with the power of antibodies to detect disease. A conventional compact disc has 5 billion diffraction-limited pits encoding digital information. The motivation behind the BioCD is to turn a disc into 5 billion micro-test-tubes to test for every type of blood protein in a few drops of blood. The science of molecular interferometry combines the physics of laser coherence, quantum optics, light-matter interactions, and surface science, with molecular biology and biomedical diagnostics. The BioCD and Art: See the BioCD at the Vancouver Art Museum|| Tutorial on Molecular Interferometry |
Following the example of integrated electronic circuits, the "lab-on-a-chip" uses micro-fabrication to create microfluidic systems that transport liquid samples through reaction and analysis chambers for biochemical assays. We are studying the fundamental physics of fluids in micron and nanometer-scale systems. The unstable fingering of invading phases in 2D random systems, and thermodynamic properties of liquids in contact with other liquids or solids, leads to strong hysteretic relationships between saturation and capillary pressure that has eluded clear theoretical explanation. Moving into three dimensions is being pursued by building porous microsystems using two-photon polymerization (2PP) laser micromachining.
Nonlinear Optics and Solid State Physics
Photorefractive Quantum Well device in a femtosecond spectral holography system. Full size
The Adaptive Optics and Biophotonics group at Purdue has developed the world's most sensitive dynamic holographic film, semiconductor devices called Photorefractive Quantum Wells (PRQW). The nonlinear optical properties of the PRQW devices lead to the largest index change per photon of any optical nonlinearity. The physics behind the PRQW involves nonlinear electronic transport, electro-optics, quantum-confined excitons, deep-level defects, space-charge fields, and coherent mixing of laser fields. Applications of PRQW devices includes adaptive interferometry, laser-based ultrasound detection, fsec dispersion compensation, and holographic optical coherence imaging.