Terahertz Spectroscopy Applied to Diagnostics in Public Health: A Review

Abstract Terahertz (THz) spectroscopy is an emerging technology that is that is bringing a number of technical breakthroughs in several scientific applications. This review aimed to describe potential applications of THz spectroscopy at the biochemistry and molecules detection for food industry, environment monitoring and diagnostics, and present the importance of such technological platform in disease control and Public Health.

Molecular Detection for Unconcentrated Gas With ppm Sensitivity Using 220-to-320-GHz Dual-Frequency-Comb Spectrometer in CMOS.

Millimeter-wave/terahertz rotational spectroscopy of polar gaseous molecules provides a powerful tool for complicated gas mixture analysis. In this paper, a 220-to-320-GHz dual-frequency-comb spectrometer in 65-nm bulk CMOS is presented, along with a systematic analysis on fundamental issues of rotational spectrometer, including the impacts of various noise mechanisms, gas cell, molecular properties, detection sensitivity, etc. Our comb spectrometer, based on a high-parallelism architecture, probes gas sample with 20 comb lines simultaneously. It does not only improve the scanning speed by 20, but also reduces the overall energy consumption to 90 mJ/point with 1 Hz bandwidth (or 0.5 s integration time). With its channelized 100-GHz scanning range and sub-kHz specificity, wide range of molecules can be detected. In the measurements, state-of-the-art total radiated power of 5.2 mW and single sideband noise figure of 14.6-19.5 dB are achieved, which further boost the scanning speed and sensitivity. Finally, spectroscopic measurements for carbonyl sulfide (OCS) and acetonitrile (CH CN) are presented. With a path length of 70 cm and 1 Hz bandwidth, the measured minimum detectable absorption coefficient reaches  cm. For OCS that enables a minimum detectable concentration of 11 ppm. The predicted sensitivity for some other molecules reaches ppm level (e.g., 3 ppm for hydrogen cyanide), or 10 ppt level if gas preconcentration with a typical gain of 10 is used.

Diagnosis of oral lichen planus from analysis of saliva samples using terahertz time-domain spectroscopy and chemometrics.

The ability to diagnose oral lichen planus (OLP) based on saliva analysis using THz time-domain spectroscopy and chemometrics is discussed. The study involved 30 patients (2 male and 28 female) with OLP. This group consisted of two subgroups with the erosive form of OLP (n = 15) and with the reticular and papular forms of OLP (n = 15). The control group consisted of six healthy volunteers (one male and five females) without inflammation in the mucous membrane in the oral cavity and without periodontitis. Principal component analysis was used to reveal informative features in the experimental data. The one-versus-one multiclass classifier using support vector machine binary classifiers was used. The two-stage classification approach using several absorption spectra scans for an individual saliva sample provided 100% accuracy of differential classification between OLP subgroups and control group.

Improvement of Terahertz Wave Radiation for InAs Nanowires by Simple Dipping into Tap Water.

We report improvement of terahertz (THz) wave radiation for Si-based catalyst-free InAs nanowires (NWs) by simple dipping into tap water (DTW). In addition, the possibility of using InAs NWs as a cost-effective method for biomedical applications is discussed by comparison to bulk InAs. The peak-to-peak current signals (PPCSs) of InAs NWs measured from THz time-domain spectroscopy increased with increasing NW height. For example, the PPCS of 10 µm-long InAs NWs was 2.86 times stronger than that of 2.1 µm-long NWs. The THz spectra of the InAs NWs obtained by applying a fast Fourier transformation to the current signals showed a main frequency of 0.5 THz, which can be applied to a variety of medical imaging systems. After the DTW process, structural variation was not observed for 2.1 µm-long InAs NWs. However, the top region of several InAs NWs with heights of 4.6 and 5.8 µm merged into a conical structure. InAs NWs with a height of 10 µm resulted in a bundle feature forming above the conical shape, where the length of bundle region was 4 µm. After the DTW process, the PPCS for 10 µm-long InAs NWs increased by 15 percent compared to that of the as-grown case.

Terahertz pulsed spectroscopy of paraffin-embedded brain glioma.

The refractive indices, absorption coefficients, and complex dielectric constants of paraffin-embedded brain glioma and normal brain tissues have been measured by a terahertz time-domain spectroscopy (THz-TDS) system in the 0.2- to 2.0-THz range. The spectral differences between gliomas and normal brain tissues were obtained. Compared with normal brain tissue, our results indicate that paraffin-embedded brain gliomas have a higher refractive index, absorption coefficient, and dielectric constant. Based on these results, the best THz frequencies for different methods of paraffin-embedded brain glioma imaging, such as intensity imaging, coherent imaging with continuum THz sources, and THz pulsed imaging with short-pulsed THz sources, are analyzed.

Long-range guided THz radiation by thin layers of water.

We propose a novel method to guide THz radiation with low losses along thin layers of water. This approach is based on the coupling of evanescent surface fields at the opposite sides of the thin water layer surrounded by a dielectric material, which leads to a maximum field amplitude at the interfaces and a reduction of the energy density inside the water film. In spite of the strong absorption of water in this frequency range, calculations show that the field distribution can lead to propagation lengths of several centimeters. By means of attenuated total reflection measurements we demonstrate the coupling of incident THz radiation to the long-range surface guided modes across a layer of water with a thickness of 24 µm. This first demonstration paves the way for THz sensing in aqueous environments.

Chirped-pulse terahertz spectroscopy for broadband trace gas sensing.

We report the first demonstration of a broadband trace gas sensor based on chirp-pulse terahertz spectroscopy. The advent of newly developed solid state sources and sensitive heterodyne detectors for the terahertz frequency range have made it possible to generate and detect precise arbitrary waveforms at THz frequencies with ultra-low phase noise. In order to maximize sensitivity, the sample gas is first polarized using sub-µs chirped THz pulses and the free inductive decays (FIDs) are then detected using a heterodyne receiver. This approach allows for a rapid broadband multi-component sensing with low parts in 10(9) (ppb) sensitivities and spectral frequency accuracy of <20 kHz in real-time. Such a system can be configured into a portable, easy to use, and relatively inexpensive sensing platform.

Terahertz sensing in corneal tissues.

This work introduces the potential application of terahertz (THz) sensing to the field of ophthalmology, where it is uniquely suited due to its nonionizing photon energy and high sensitivity to water content. Reflective THz imaging and spectrometry data are reported on ex-vivo porcine corneas prepared with uniform water concentrations using polyethylene glycol (PEG) solutions. At 79% water concentration by mass, the measured reflectivity of the cornea was 20.4%, 14.7%, 11.7%, 9.6%, and 7.4% at 0.2, 0.4, 0.6, 0.8, and 1 THz, respectively. Comparison of nine corneas hydrated from 79.1% to 91.5% concentration by mass demonstrated an approximately linear relationship between THz reflectivity and water concentration, with a monotonically decreasing slope as the frequency increases. The THz-corneal tissue interaction is simulated with a Bruggeman model with excellent agreement. THz applications to corneal dystrophy, graft rejection, and refractive surgery are examined from the context of these measurements.

Coupling terahertz radiation between sub-wavelength metal-metal waveguides and free space using monolithically integrated horn antennae.

Broadband horn antennae are presented that efficiently couple terahertz radiation between sub-wavelength metal-metal waveguides and free space. Sub-picosecond terahertz pulses were coupled into and out from sub-wavelength parallel-plate waveguides by using the horn antennae in a terahertz time-domain spectrometer. Monolithic antennae were fabricated at the facets of metal-metal terahertz quantum cascade lasers, and laser action was observed for devices emitting at 1.4 THz, 2.3 THz and 3.2 THz. A good far-field laser radiation pattern (FWHM less than 11 degrees) is obtained as a result of the significant expansion of the optical mode by the antenna.

Terahertz pulsed spectroscopy of freshly excised human breast cancer.

The complex refractive indices of freshly excised healthy breast tissue and breast cancers collected from 20 patients were measured in the range of 0.15 - 2.0 THz using a portable terahertz pulsed transmission spectrometer. Histology was performed to classify the tissue samples as healthy adipose tissue, healthy fibrous breast tissue, or breast cancers. The average complex refractive index was determined for each group and it was found that samples containing cancer had a higher refractive index and absorption coefficient. The terahertz properties of the tissues were also used to simulate the impulse response functions expected when imaging breast tissue in a reflection geometry as in terahertz pulsed imaging (TPI). Our results indicate that both TPS and TPI can be used to distinguish between healthy adipose breast tissue, healthy fibrous breast tissue and breast cancer due to the differences in the fundamental optical properties.

Resonant tuning fork detector for THz radiation.

THz-sensing is an emerging technology that would be advantageous for a variety of applications in industry, biology, biochemistry and security, if small and convenient to use sources and detectors would be readily available. However, most of them are bulky, complicate to operate, and need cryogenic cooling. Here we present a new detection scheme that is versatile enough to detect electro-magnetic radiation within the whole spectrum, can be easily applied to the THz-range, and operates at room temperature. The mechanism is based on the resonant excitation of a quartz tuning fork.

Towards medical terahertz sensing of skin hydration.

Terahertz imaging has shown promise as a tool for noninvasive in-vivo detection of skin abnormalities, including skin cancer, burns, scars, and wounds due to its low non-ionizing photon energy and ability to penetrate clothing and gauze. This study examines whether low-level bulk differences in the water content between hyperhydrated and dehydrated skin can be detected using a scanning, reflective THz imaging system. Our results show an 8.7 x difference in the THz reflectivity between hyperhydrated and dehydrated specimens of chicken skin. The results provide further evidence that water concentration is the primary contrast mechanism in reflective THz biomedical imaging.