Terahertz sensor based on a three-dimensional double I-type metamaterial integrated microfluidic channel.

Terahertz metamaterial sensors have received extensive attention in biosensing applications. However, sensitivity toward terahertz frequencies emitted by liquid samples remains challenging because of the strong absorption of terahertz waves by water. Here, we present a highly sensitive terahertz sensor based on a three-dimensional double I-type metamaterial integrated microfluidic channel. The designed sensor produces an inductive-capacitive (LC) resonance with a high quality factor of approximately 72, while demonstrating a maximum sensitivity of 832 GHz/RIU. Furthermore, we analyzed the relationship between the resonance frequency and ethanol concentration. These findings would promote the application of terahertz technology in label-free and rapid biomedical sensing as well as substance detection.

Terahertz probing of sunflower leaf multilayer organization.

We analyze the multilayer structure of sunflower leaves from Terahertz data measured in the time-domain at a ps scale. Thin film reverse engineering techniques are applied to the Fourier amplitude of the reflected and transmitted signals in the frequency range f < 1.5 Terahertz (THz). Validation is first performed with success on etalon samples. The optimal structure of the leaf is found to be a 8-layer stack, in good agreement with microscopy investigations. Results may open the door to a complementary classification of leaves.

Negative curvature hollow-core anti-resonant fiber for terahertz sensing.

Hollow-core fibers are advantageous for chemical sensing as they facilitate liquid infiltration into the core over conventional porous core fiber. In addition, the requirement of less bulk material significantly decreases the effective material loss (EML). In this paper, a six circular cladding tube negative curvature hollow-core fiber (NC-HCF) is proposed for chemical sensing. Five different chemicals including chloroform, polylactic acid, CCL3, glycerin, and benzene are proposed to fill the core of the NC-HCF, and sensitivities are evaluated by full vector finite element method-based COMSOL software. Numerical results reveal that the proposed sensor exhibits very high relative sensitivity in a wide range of frequency. The fabrication of the proposed fiber is feasible by existing fabrication facilities as it contains realistic fabrication parameters. Hence, the proposed sensor can potentially be used as a chemical sensor especially in the medical, food, and industrial sectors as the five chemicals mentioned above carry great medical and food significance.

Single cell imaging with near-field terahertz scanning microscopy.

OBJECTIVES: Terahertz (THz)-based imaging techniques hold great potential for biological and biomedical applications, which nevertheless are hampered by the low spatial resolution of conventional THz imaging systems. In this work, we report a high-performance photoconductive antenna microprobe-based near-field THz time-domain spectroscopy scanning microscope. MATERIALS AND METHODS: A single watermelon pulp cell was prepared on a clean quartz slide and covered by a thin polyethylene film. The high performance near-field THz microscope was developed based on a coherent THz time-domain spectroscopy system coupled with a photoconductive antenna microprobe. The sample was imaged in transmission mode. RESULTS: We demonstrate the direct imaging of the morphology of single watermelon pulp cells in the natural dehydration process with our near-field THz microscope. CONCLUSIONS: Given the label-free and non-destructive nature of THz detection techniques, our near-field microscopy-based single-cell imaging approach sheds new light on studying biological samples with THz.

Protein and RNA dynamical fingerprinting.

Protein structural vibrations impact biology by steering the structure to functional intermediate states; enhancing tunneling events; and optimizing energy transfer. Strong water absorption and a broad continuous vibrational density of states have prevented optical identification of these vibrations. Recently spectroscopic signatures that change with functional state were measured using anisotropic terahertz microscopy. The technique however has complex sample positioning requirements and long measurement times, limiting access for the biomolecular community. Here we demonstrate that a simplified system increases spectroscopic structure to dynamically fingerprint biomacromolecules with a factor of 6 reduction in data acquisition time. Using this technique, polarization varying anisotropy terahertz microscopy, we show sensitivity to inhibitor binding and unique vibrational spectra for several proteins and an RNA G-quadruplex. The technique's sensitivity to anisotropic absorbance and birefringence provides rapid assessment of macromolecular dynamics that impact biology.

Imaging brain tissue slices with terahertz near-field microscopy.

Photoconductive antenna microprobe (PCAM)-based terahertz (THz) near-field imaging technique is promising for biomedical detection due to its excellent biocompatibility and high resolution; yet it is limited by its imaging speed and the difficulty in the control of the PCAM tip-sample separation. In this work, we successfully realized imaging of mouse brain tissue slices using an improved home-built PCAM-based THz near-field microscope. In this system, the imaging speed was enhanced by designing and applying a voice coil motor-based delay-line. The tip-sample separation control was implemented by developing an image analysis-based technique. Compared with conventional PCAM-based THz near-field systems, our improved system is 100 times faster in imaging speed and the tip-sample separation can be controlled to a few micrometers (e.g., 3 µm), satisfying the requirements of THz near-field imaging of biological samples. It took about ~30 min (not the tens of hours it took to acquire the same kind of image previously) to collect a THz near-field image of brain tissue slices of BALb/c mice (500 µm × 500 µm) with pixel size of 20 µm × 20 µm. The results show that the mouse brain slices can be properly imaged and different regions in the slices (i.e., the corpus callosum region and the cerebrum region) can be identified unambiguously. Evidently, the work demonstrated here provides not only a convincing example but a useful technique for imaging biological samples with THz near-field microscopy. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2741, 2019.

Fabrication of Nanopillar-Based Split Ring Resonators for Displacement Current Mediated Resonances in Terahertz Metamaterials.

Terahertz (THz) split ring resonator (SRR) metamaterials (MMs) has been studied for gas, chemical, and biomolecular sensing applications because the SRR is not affected by environmental characteristics such as the temperature and pressure surrounding the resonator. Electromagnetic radiation in THz frequencies is biocompatible, which is a critical condition especially for the application of the biomolecular sensing. However, the quality factor (Q-factor) and frequency responses of traditional thin-film based split ring resonator (SRR) MMs are very low, which limits their sensitivities and selectivity as sensors. In this work, novel nanopillar-based SRR MMs, utilizing displacement current, are designed to enhance the Q-factor up to 450, which is around 45 times higher than that of traditional thin-film-based MMs. In addition to the enhanced Q-factor, the nanopillar-based MMs induce a larger frequency shifts (17 times compared to the shift obtained by the traditional thin-film based MMs). Because of the significantly enhanced Q-factors and frequency shifts as well as the property of biocompatible radiation, the THz nanopillar-based SRR are ideal MMs for the development of biomolecular sensors with high sensitivity and selectivity without inducing damage or distortion to biomaterials. A novel fabrication process has been demonstrated to build the nanopillar-based SRRs for displacement current mediated THz MMs. A two-step gold (Au) electroplating process and an atomic layer deposition (ALD) process are used to create sub-10 nm scale gaps between Au nanopillars. Since the ALD process is a conformal coating process, a uniform aluminum oxide (Al2O3) layer with nanometer-scale thickness can be achieved. By sequentially electroplating another Au thin film to fill the spaces between Al2O3 and Au, a close-packed Au-Al2O3-Au structure with nano-scale Al2O3 gaps can be fabricated. The size of the nano-gaps can be well defined by precisely controlling the deposition cycles of the ALD process, which has an accuracy of 0.1 nm.

Terahertz imaging for early screening of diabetic foot syndrome: A proof of concept.

Most people with diabetes suffer some deterioration of the feet. Diabetic foot syndrome causes ulceration in about 15% of cases and such deterioration leads to amputation in about 2.5% of diabetic patients, diminishing their quality of life and generating extraordinary costs for patients and public health systems. Currently, there is no objective method for the detection of diabetic foot syndrome in its early stages. We propose terahertz imaging as a method for the evaluation of such deterioration. This screening method could aid the prevention and medical treatment of this condition in the future.

Measurement of the Intertablet Coating Uniformity of a Pharmaceutical Pan Coating Process With Combined Terahertz and Optical Coherence Tomography In-Line Sensing.

We present in-line coating thickness measurements acquired simultaneously using 2 independent sensing modalities: terahertz pulsed imaging (TPI) and optical coherence tomography (OCT). Both techniques are sufficiently fast to resolve the coating thickness of individual pharmaceutical tablets in situ during the film coating operation, and both techniques are direct structural imaging techniques that do not require multivariate calibration. The TPI sensor is suitable to measure coatings greater than 50 µm and can penetrate through thick coatings even in the presence of pigments over a wide range of excipients. Due to the long wavelength, terahertz radiation is not affected by scattering from dust within the coater. In contrast, OCT can resolve coating layers as thin as 20 µm and is capable of measuring the intratablet coating uniformity and the intertablet coating thickness distribution within the coating pan. However, the OCT technique is less robust when it comes to the compatibility with excipients, dust, and potentially the maximum coating thickness that can be resolved. Using a custom-built laboratory scale coating unit, the coating thickness measurements were acquired independently by the TPI and OCT sensors throughout a film coating operation. Results of the in-line TPI and OCT measurements were compared against one another and validated with off-line TPI and weight gain measurements. Compared with other process analytical technology sensors, such as near-infrared and Raman spectroscopy, the TPI and OCT sensors can resolve the intertablet thickness distribution based on sampling a significant fraction of the tablet populations in the process. By combining 2 complementary sensing modalities, it was possible to seamlessly monitor the coating process over the range of film thickness from 20 µm to greater than 250 µm.

Study of transmittance and reflectance spectra of the cornea and the sclera in the THz frequency range.

An adequate water balance (hydration extent) is one of the basic factors of normal eye function, including its external shells: the cornea and the sclera. Adequate control of corneal and scleral hydration is very important for early diagnosis of a variety of eye diseases, stating indications for and contraindications against keratorefractive surgeries and the choice of contact lens correction solutions. THz systems of creating images in reflected beams are likely to become ideal instruments of noninvasive control of corneal and scleral hydration degrees. This paper reports on the results of a study involving transmittance and reflectance spectra for the cornea and the sclera of rabbit and human eyes, as well as those of the rabbit eye, in the frequency range of 0.13 to 0.32 THz. The dependence of the reflectance coefficient of these tissues on water mass percentage content was determined. The experiments were performed on three corneas, three rabbit scleras, two rabbit eyes, and three human scleras. The preliminary results demonstrate that the proposed technique, based on the use of a continuous THz radiation, may be utilized to create a device for noninvasive control of corneal and scleral hydration, which has clear potential of broad practical application.

Noninvasive, near-field terahertz imaging of hidden objects using a single-pixel detector.

Terahertz (THz) imaging can see through otherwise opaque materials. However, because of the long wavelengths of THz radiation (λ = 400 µm at 0.75 THz), far-field THz imaging techniques suffer from low resolution compared to visible wavelengths. We demonstrate noninvasive, near-field THz imaging with subwavelength resolution. We project a time-varying, intense (>100 µJ/cm(2)) optical pattern onto a silicon wafer, which spatially modulates the transmission of synchronous pulse of THz radiation. An unknown object is placed on the hidden side of the silicon, and the far-field THz transmission corresponding to each mask is recorded by a single-element detector. Knowledge of the patterns and of the corresponding detector signal are combined to give an image of the object. Using this technique, we image a printed circuit board on the underside of a 115-µm-thick silicon wafer with ~100-µm (λ/4) resolution. With subwavelength resolution and the inherent sensitivity to local conductivity, it is possible to detect fissures in the circuitry wiring of a few micrometers in size. THz imaging systems of this type will have other uses too, where noninvasive measurement or imaging of concealed structures is necessary, such as in semiconductor manufacturing or in ex vivo bioimaging.

Early detection of skin cancer via terahertz spectral profiling and 3D imaging.

Terahertz scanning reflectometry, terahertz 3D imaging and terahertz time-domain spectroscopy have been used to identify features in human skin biopsy samples diagnosed for basal cell carcinoma (BCC) and compared with healthy skin samples. It was found from the 3D images that the healthy skin samples exhibit regular cellular pattern while the BCC skin samples indicate lack of regular cell pattern. The skin is a highly layered structure organ; this is evident from the thickness profile via a scan through the thickness of the healthy skin samples, where, the reflected intensity of the terahertz beam exhibits fluctuations originating from different skin layers. Compared to the healthy skin samples, the BCC samples' profiles exhibit significantly diminished layer definition; thus indicating a lack of cellular order. In addition, terahertz time-domain spectroscopy reveals significant and quantifiable differences between the healthy and BCC skin samples. Thus, a combination of three different terahertz techniques constitutes a conclusive route for detecting the BCC condition on a cellular level compared to the healthy skin.

Efficient Terahertz detection in black-phosphorus nano-transistors with selective and controllable plasma-wave, bolometric and thermoelectric response.

The ability to convert light into an electrical signal with high efficiencies and controllable dynamics, is a major need in photonics and optoelectronics. In the Terahertz (THz) frequency range, with its exceptional application possibilities in high data rate wireless communications, security, night-vision, biomedical or video-imaging and gas sensing, detection technologies providing efficiency and sensitivity performances that can be "engineered" from scratch, remain elusive. Here, by exploiting the inherent electrical and thermal in-plane anisotropy of a flexible thin flake of black-phosphorus (BP), we devise plasma-wave, thermoelectric and bolometric nano-detectors with a selective, switchable and controllable operating mechanism. All devices operates at room-temperature and are integrated on-chip with planar nanoantennas, which provide remarkable efficiencies through light-harvesting in the strongly sub-wavelength device channel. The achieved selective detection (∼5-8 V/W responsivity) and sensitivity performances (signal-to-noise ratio of 500), are here exploited to demonstrate the first concrete application of a phosphorus-based active THz device, for pharmaceutical and quality control imaging of macroscopic samples, in real-time and in a realistic setting.

Tunable terahertz wave generation through a bimodal laser diode and plasmonic photomixer.

We demonstrate a compact, robust, and stable terahertz source based on a novel two section digital distributed feedback laser diode and plasmonic photomixer. Terahertz wave generation is achieved through difference frequency generation by pumping the plasmonic photomixer with two output optical beams of the two section digital distributed feedback laser diode. The laser is designed to offer an adjustable terahertz frequency difference between the emitted wavelengths by varying the applied currents to the laser sections. The plasmonic photomixer is comprised of an ultrafast photoconductor with plasmonic contact electrodes integrated with a logarithmic spiral antenna. We demonstrate terahertz wave generation with 0.15-3 THz frequency tunability, 2 MHz linewidth, and less than 5 MHz frequency stability over 1 minute, at useful power levels for practical imaging and sensing applications.

Generation of arbitrary order Bessel beams via 3D printed axicons at the terahertz frequency range.

We present the generation of arbitrary order Bessel beams at 0.3 THz through the implementation of suitably designed axicons based on 3D printing technology. The helical axicons, which possess thickness gradients in both radial and azimuthal directions, can convert the incident Gaussian beam into a high-order Bessel beam with spiral phase structure. The evolution of the generated Bessel beams are characterized experimentally with a three-dimensional field scanner. Moreover, the topological charges carried by the high-order Bessel beams are determined by the fork-like interferograms. This 3D-printing-based Bessel beam generation technique is useful not only for THz imaging systems with zero-order Bessel beams but also for future orbital-angular-momentum-based THz free-space communication with higher-order Bessel beams.

Single-channel prototype terahertz endoscopic system.

We demonstrate the design and development of an innovative single-channel terahertz (THz) prototype endoscopic imaging system based on flexible metal-coated THz waveguides and a polarization specific detection technique. The continuous-wave (CW) THz imaging system utilizes a single channel to transmit and collect the reflected intrinsic THz signal from the sample. Since the prototype system relies on a flexible waveguide assembly that is small enough in diameter, it can be readily integrated with a conventional optical endoscope. This study aims to show the feasibility of waveguide enabled THz imaging. We image various objects in transmission and reflection modes. We also image normal and cancerous colonic tissues in reflectance mode using a polarization specific imaging technique. The resulting cross-polarized THz reflectance images showed contrast between normal and cancerous colonic tissues at 584 GHz. The level of contrast observed using endoscopic imaging correlates well with contrast levels observed in ex vivo THz reflectance studies of colon cancer. This indicates that the single-channel flexible waveguide-based THz endoscope presented here represents a significant step forward in clinical endoscopic application of THz technology to aid in in vivo cancer screening.

High-speed terahertz imaging toward food quality inspection.

In contrast to conventional x-ray food inspection systems that have difficulty in detecting low-density materials, a terahertz imaging system can even identify insects and plastics embedded in a food matrix. A reflection-mode continuous-wave terahertz imaging system was therefore developed for application to food quality inspection, which requires fast, compact, and low-cost detection. High-speed operation of the terahertz imaging system was achieved through the use of a beam-steering tool. A reasonable compromise between the spatial resolution and the scan length of an aspheric f-theta scanning lens could be achieved by optimizing the lens parameters.

Stabilization method for signal drifts in terahertz chemical microscopy.

A stabilization method for signal drifts in terahertz chemical microscopy (TCM) due to unexpected chemical potential changes in sample solutions was proposed and developed. The sensing plate was separated into two areas: a detection area and a control area. The detection area radiated a THz pulse whose amplitude was related to both the chemical reactions in the sample solutions and unexpected potential changes. The THz pulse from the control area was related only to unexpected potential changes. In the proposed system, the THz pulse from each area was interfered and detected. By adjusting the timing of the positive peak of the THz pulse from the detection area and the negative peak of the THz pulse from the control area, we detected the difference in both peaks as the interference signal. Thus, the signal deviation of 390 when the environmental condition changes in the temperature range of 38 °C and the pH range of 8.33 was stabilized to be the signal deviation of 31. As the result, the TCM with stabilization method could detect the signal shift of 121 when the 275-nmol/L immunoglobulin G was immobilized on the sensing plate.

CW-THz vector spectroscopy and imaging system based on 1.55-µm fiber-optics.

We present a continuous-wave terahertz (THz) vector spectroscopy and imaging system based on a 1.5-µm fiber optic uni-traveling-carrier photodiode and InGaAs photo-conductive receiver. Using electro-optic (EO) phase modulators for THz phase control with shortened optical paths, the system achieves fast vector measurement with effective phase stabilization. Dynamic ranges of 100 dB · Hz and 75 dB · Hz at 300 GHz and 1 THz, and phase stability of 1.5° per minute are obtained. With the simultaneous measurement of absorbance and relative permittivity, we demonstrate non-destructive analyses of pharmaceutical cocrystals inside tablets within a few minutes.

Terahertz single pixel imaging with an optically controlled dynamic spatial light modulator.

We present a single pixel terahertz (THz) imaging technique using optical photoexcitation of semiconductors to dynamically and spatially control the electromagnetic properties of a semiconductor mask to collectively form a THz spatial light modulator (SLM). By co-propagating a THz and collimated optical laser beam through a high-resistivity silicon wafer, we are able to modify the THz transmission in real-time. By further encoding a spatial pattern on the optical beam with a digital micro-mirror device (DMD), we may write masks for THz radiation. We use masks of varying complexities ranging from 63 to 1023 pixels and are able to acquire images at speeds up to 1/2 Hz. Our results demonstrate the viability of obtaining real-time and high-fidelity THz images using an optically controlled SLM with a single pixel detector.