T-rays offer potential for earlier diagnosis of melanoma

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Michael Woods
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202-872-6293 American Chemical Society
T-rays offer potential for earlier diagnosis of melanoma INDIANAPOLIS, Sept. 11, 2013 — The technology that peeks underneath clothing at airport security screening check points has great potential for looking underneath human skin to diagnose cancer at its earliest and most treatable stages, a scientist said here today.

The report on efforts to use terahertz radiation — "T-rays" — in early diagnosis of skin cancer was part of the 246th National Meeting & Exposition of the American Chemical Society, the world's largest scientific society. Almost 7,000 reports on new advances in science and other topics are on the schedule for the meeting. It continues here through Thursday in the Indiana Convention Center and downtown hotels.

Anis Rahman, Ph.D., who spoke on the topic, explained that malignant melanoma, the most serious form of skin cancer, starts in pigment-producing cells located in the deepest part of the epidermis. That's the outer layer of the skin. Biochemical changes that are hallmarks of cancer occur in the melanocytes long before mole-like melanomas appear on the skin.

"Terahertz radiation is ideal for looking beneath the skin and detecting early signs of melanoma," Rahman said. "T-rays are different from X-rays, which are 'ionizing' radiation that can cause damage. T-rays are a form of 'non-ionizing' radiation, like ordinary visible light, but they can be focused harmlessly below into the body and capture biochemical signatures of events like the start of cancer."

T-rays occupy a niche in the spectrum of electromagnetic radiation, which includes X-rays and visible light, between microwaves like those used in kitchen ovens and the infrared rays used in TV remote controls. One of the advantages of T-rays is that they penetrate only a few millimeters through cloth, skin and other non-metallic material. Ten sheets of printer paper would be about 1 millimeter thick. This key characteristic has led to their use in quality control in the pharmaceutical industry to check the surface integrity of pills and capsules, in homeland security to remotely frisk underneath clothes, and as a non-destructive way of probing beneath the top layers of famous paintings and other culturally significant artwork.

Rahman, president and chief technology officer of Applied Research & Photonics in Harrisburg, Pa., said that medical imaging is one of their newest and most promising potential uses. He described research focusing T-rays through donated samples of human skin that suggest the technology could be valuable in diagnosing melanoma.

In addition to developing T-rays for cancer diagnostics, Rahman's team has successfully harnessed them to measure the real-time absorption rates and penetration in the outer layer of skin of topically applied drugs and shampoo — measurements that until now had not been possible.

Other wide-ranging applications include the detection of early stages of tooth decay, trace pesticides on produce, flaws in pharmaceutical tablet coatings, and concealed weapons under clothing, as well as testing the effectiveness of skin cosmetics. Rahman's talk was part of a symposium entitled "Terahertz Spectroscopy: Problem Solving for the 21st Century," being held at the ACS meeting. Abstracts of those talks appear below.

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Abstracts

Terahertz subsurface imaging for biomedical applications Anis Rahman, a.rahman@arphotonics.net, Aunik K Rahman. Terahertz, Applied Research & Photonics, Harrisburg, Pennsylvania 17111, United States

Terahertz radiation can be selectively focused on an interior layer of a substrate. This gives an advantage to inspect interior features in a non-invasive way. Terahertz being non-ionizing, is also safe for in-vivo use. Thus a high resolution imaging capability may find direct application in diagnostics for melanoma and other disorder under the skin. It can be further developed for early detection of breast cancer, for example. Other applications include defects detection of semiconductor wafers to minimize rejection problem. Fig. 1 & Fig. 2 show a volume tomogram of a wafer and surface tomogram of a substrate. Defects may be identified and quantified by comparing images of contaminated areas with that of good areas. This talk will outline the principle of this new line of measurement capabilities with practical examples.

Non-interaction of waves in applied spectrometry Chandrasekhar Roychoudhuri1, chandra@phys.uconn.edu, Anis Rahman2. (1) Photonics Lab. U-5192, Univ. of Connecticut, 54 Ahern Lane, Storrs, CT 06269-5192, United States, (2) Terahertz, Applied Research & Photonics, Harrisburg, Pennsylvania 17111, United States

Theories of physics are constructed by using human invented mathematical logics while enforcing quantitative equality between the cause and the effect, mediated by some real physical processes; which are our interpretations. These interpretations are not 100% congruent with the ontological cosmic logics. So we must keep on improving theories by iterating. The cause is defined by our hypothesis logics; the effect is defined through reproducible measurements and the physical processes are constructed by our imaginations, since the micro universe is still invisible to our technologies. How are these connected to chemistry, biology and evolution? Sustained evolution relies upon invention of tools and technologies, needed for gathering food and other comforts. Technology inventions are nothing but emulation of nature allowed physical processes in novel ways, or in novel combinations. Unfortunately, modern physics teaches us to stop enquiring, "Do electrons really follow orbits, or such processes?" This paper attempts to bring back causality in physics, by developing a causal theory of spectrometry to obtain super resolution, orders of magnitude better than δν/δt≥1. We follow the propagation process of the carrier frequency contained in a time-finite pulse through a spectrometer, instead of the non-causal Fourier monochromatic modes that exists for all time, requiring infinite amount of energy. Then we follow the physical processes behind the emergence of superposition effect registered as some physical transformation in a detector due to simultaneous stimulations induced on it by multiple EM waves generated by the interferometer (or the spectrometer). One then discovers, subtly hidden in Maxwell's wave equation, the NIW-property (Non-Interaction of Waves). Like Occam's razor, the NIW-property eliminates a number of unnecessary non-causal hypotheses of Quantum Mechanics, while explicitly recognizes the detector's intrinsic time-averaging and detection circuit's time-integration properties. These are essential for proper interpretation of spectral data in all spectrometry, including the field of Terahertz.

Terahertz spectroscopy of crystalline pharmaceuticals: Experiment and theory Timothy M Korter, tmkorter@syr.edu, Department of Chemistry, Syracuse University, Syracsue, NY 13244-4100, United States

The terahertz (THz) or far-infrared region of the electromagnetic spectrum spans frequencies from 0.1 to 10 THz (1 THz ∼ 33.33 cm-1). The majority of crystalline solids exhibit characteristic lattice vibrations toward the lower limit (≤100 cm-1) of this range, making THz spectroscopy a powerful analytical tool for probing the intermolecular interactions within molecular crystals. Specific applications of THz spectroscopy relevant to the pharmaceutical industry will be discussed in this seminar, including studies regarding the detection of drug polymorphs, elucidation of difficult crystal structures, and the analysis of amorphous/crystalline mixtures. Despite recent experimental advances in the field, understanding the THz spectra of crystalline solids remains challenging, and identifying the complex vibrational motions giving rise to absorptions in this region is not trivial. Computational methods utilizing solid-state density functional theory augmented with corrections for weak London dispersion forces will be presented, revealing the origins of these low-frequency vibrational motions, and providing much needed physical insights into the experimental observations.

Terahertz responses of supramolecular assemblies: Applications to nanomedicine Ross A Quick1, raquick@indiana.edu, Elliot R Brown2, Weidong Zhang2, Leamon Viveros2, Peter Ortoleva1. (1) Department of Chemistry, Indiana University, Bloomington, IN 47405, United States, (2) Department of Electrical Engineering, Wright State University, Dayton, OH 45435, United States

Autonomous and electrically driven THz structural fluctuations of virus-like and other supramolecular assemblies are analyzed using a computational approach. Both structure-wide and local oscillatory responses are discussed. The computational method is based on traditional molecular dynamics (MD) and on multiscale MD, both of which preserve all-atom detail and avoid calibration with experimental data through the use of an interatomic force field. The cross-talk among processes from the atomic to the ten nanometer scales are accounted for in the simulations. Applications in nanomedicine and materials are discussed, as are spectroscopic signatures. The virus-like particle consisting of L1 capsid proteins of human papillomavirus is a major demonstration system. Results for proteins and supramolecular assemblies of enterovirus, poliovirus, and hepatitis B virus are also presented, as is the application of this technology to the prediction of the viability of a given VLP as an antiviral vaccine.

Terahertz spectroscopic characterization of protein vaccine antigens and saponin-derived adjuvant macromolecules Anis Rahman1, a.rahman@arphotonics.net, Aunik K Rahman1, Dale Ruby2, Trevor Broadt2. (1) Terahertz, Applied Research & Photonics, Harrisburg, Pennsylvania 17111, United States, (2) Process Analytics, Biopharmaceutical Development Program, SAIC-Frederick, Frederick, P.O. Box B, MD 21701, United States

Biopharmaceutical compounds such as recombinant viral protein antigens and saponin adjuvants are candidates for vaccination and treatment of virally induced cancers. These samples were analyzed by terahertz time domain spectroscopy on a standard polyethylene background. Aliquot 100 µL solution of each was dispensed on the PE card, allowed to dry overnight at room temperature. Dry sample weight was determined by a microbalance. The terahertz spectrometer was calibrated with respect to a blank polyethylene card. The biopharmaceutical samples spectra were then acquired one at a time (Fig. 1). It was found that the compounds under study exhibit rich spectral features over the range of 0.1THz to ~34THz (Fig. 2). Some of these peaks have been attempted to explain in terms of their molecular structure and chemical properties. These results will be discussed with exemplary spectra.