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Digital Holography and BioInterferometry

The Digital Holography, Interferometry and BioPhotonics group, directed by Professor David D. Nolte, applies the ultimate 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. Examples include the Bio-CD (Biological Compact Disks) that rely on diffraction of lasers from antibodies on spinning discs, to real-time video flythroughs of rat bone-cancer tumors using digital holography.

 

New 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

Link to Amazon.com

 

Holographic Optical Coherence Imaging

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

 

The BioCD

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 |

 

 

 

 

 

Microfluidics

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

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.