Highly integrated automatic injection terahertz microfluidic biosensor based on metasurface and LT-GaAs photoconductive antenna.

In this paper, a highly integrated terahertz (THz) biosensor is proposed and implemented, which pioneered the preparation of low-temperature gallium arsenide (LT-GaAs) thin film photoconductive antenna (PCA) on the sensor for direct generation and detection of THz waves, simplifying complex terahertz time-domain spectroscopy (THz-TDS) systems. A latch type metasurface is deposited in the detection region to produce a resonance absorption peak at 0.6 THz that is independent of polarisation. Microfluidics is utilised and automatic injection is incorporated to mitigate the experimental effects of hydrogen bond absorption of THz waves in aqueous-based environment. Additionally, cell damage is minimised by regulating the cell flow rate. The biosensor was utilised to detect the concentration of three distinct sizes of bacteria with successful results. The assay was executed as a proof of concept to detect two distinct types of breast cancer cells. Based on the experimental findings, it has been observed that the amplitude and blueshift of the resonance absorption peaks have the ability to identify and differentiate various cancer cell types. The findings of this study introduce a novel approach for developing microfluidic THz metasurface biosensors that possess exceptional levels of integration, sensitivity, and rapid label-free detection capabilities.

Highly Sensitive Terahertz Metasurface Based on Electromagnetically Induced Transparency-Like Resonance in Detection of Skin Cancer Cells.

Terahertz (THz) metasurfaces based on high Q-factor electromagnetically induced transparency-like (EIT-like) resonances are promising for biological sensing. Despite this potential, they have not often been investigated for practical differentiation between cancerous and healthy cells. The present methodology relies mainly on refractive index sensing, while factors of transmission magnitude and Q-factor offer significant information about the tumors. To address this limitation and improve sensitivity, we fabricated a THz EIT-like metasurface based on asymmetric resonators on an ultra-thin and flexible dielectric substrate. Bright-dark modes coupling at 1.96 THz was experimentally verified, and numerical results and theoretical analysis were presented. An enhanced theoretical sensitivity of 550 GHz/RIU was achieved for a sample with a thickness of 13 µm due to the ultra-thin substrate and novel design. A two-layer skin model was generated whereby keratinocyte cell lines were cultured on a base of collagen. When NEB1-shPTCH (basal cell carcinoma (BCC)) were switched out for NEB1-shCON cell lines (healthy) and when BCC's density was raised from 1 × 105 to 2.5 × 105, a frequency shift of 40 and 20 GHz were observed, respectively. A combined sensing analysis characterizes different cell lines. The findings may open new opportunities for early cancer detection with a fast, less-complicated, and inexpensive method.

Highly sensitive detection of plant growth regulators by using terahertz time-domain spectroscopy combined with metamaterials.

The rapid and sensitive detection of plant-growth-regulator (PGR) residue is essential for ensuring food safety for consumers. However, there are many disadvantages in current approaches to detecting PGR residue. In this paper, we demonstrate a highly sensitive PGR detection method by using terahertz time-domain spectroscopy combined with metamaterials. We propose a double formant metamaterial resonator based on a split-ring structure with titanium-gold nanostructure. The metamaterial resonator is a split-ring structure composed of a titanium-gold nanostructure based on polyimide film as the substrate. Also, terahertz spectral response and electric field distribution of metamaterials under different analyte thickness and refractive index were investigated. The simulation results showed that the theoretical sensitivity of resonance peak 1 and peak 2 of the refractive index sensor based on our designed metamaterial resonator approaches 780 and 720 gigahertz per refractive index unit (GHz/RIU), respectively. In experiments, a rapid solution analysis platform based on the double formant metamaterial resonator was set up and PGR residues in aqueous solution were directly and rapidly detected through terahertz time-domain spectroscopy. The results showed that metamaterials can successfully detect butylhydrazine and N-N diglycine at a concentration as low as 0.05 mg/L. This study paves a new way for sensitive, rapid, low-cost detection of PGRs. It also means that the double formant metamaterial resonator has significant potential for other applications in terahertz sensing.

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 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.

Detection of single human hairs with a terahertz nonlinear quantum cascade laser.

We report the demonstration of imaging of a single human hair with a terahertz quantum cascade laser (THz-QCL) source based on intracavity difference-frequency generation. A single human hair whose diameter was about 100 µm was detected using the THz-QCL source operating at 240 K, of which the THz beam had a linear polarization. The results show that the THz image of a human hair clearly depends on the polarization direction of the THz beam. The THz QCL sources that are capable of room temperature operation will be useful for detection of small foreign objects like human hairs.

Rapid and label-free metamaterial-based biosensor for fatty acid detection with terahertz time-domain spectroscopy.

A rapid method for detecting fatty acids (FAs) using terahertz time-domain spectroscopy (THz-TDS) technology combined with a metamaterial-based THz sensor was developed. We measured the THz responses to oleic acid, linoleic acid and α-linoleic acid with different numbers of double-bond, α-linoleic acid and γ-linoleic acid with different conformations. In addition, in order to explore the reason for the observed redshifts of the resonance frequencies of the four FAs, the dielectric constants of the FAs were measured in the THz region. Furthermore, the four fatty acids were also attempted to be identified by Raman spectroscopy, which was difficult to accomplish unambiguously because of the effect of fluorescence. This result thus demonstrates the power and usefulness of metamaterial-assisted THz-TDS in the rapid determination of the FAs, and its potential as a versatile tool for investigation of biological metabolism, and for food product quality, safety inspection and control.

Determination of invert syrup adulterated in acacia honey by terahertz spectroscopy with different spectral features.

BACKGROUND: Invert syrup is a common adulterant in honey falsification, thus generating risk for consumers. Most of the methods developed are tedious and time-consuming for manufactures and consumers. However, terahertz spectroscopy provides analytical information in a simple, rapid, and environmentally friendly manner. Subsequently, 3 kinds of terahertz spectroscopic characteristics data, the absorption coefficient, the slope of the absorption coefficient spectra, and the area of the absorption coefficient spectra, were employed for determination of acacia honey adulterated with invert syrup. RESULTS: Single linear regression (SLR) models with different terahertz spectroscopic features were adopted to predict the syrup adulterant proportion in acacia honey. The best SLR model used the area of the absorption coefficient, displaying an adjusted correlation coefficient of 0.985 and a root-mean-square error of 3.201. Meanwhile, multiple linear regression (MLR) models using a successive projections algorithm for variables selection were implemented. The MLR model considered the integral area of the absorption coefficient spectra, as the inputs yielded the best result with less variables selected, higher R c 2 and R p 2 , lower root-mean-square error of calibration and prediction, as well as higher residual predictive deviation. CONCLUSIONS: The results indicate terahertz spectroscopy combined with the integral area of the absorption coefficient spectra is reliable enough for invert syrup proportion quantification in acacia honey and is also a rapid and nondestructive determination method for other honey adulterants. © 2019 Society of Chemical Industry.

A sensitive and selective terahertz sensor for the fingerprint detection of lactose.

Special recognition to molecules is essential for many biochemical processes, thus highly sensitive sensing methods for molecule recognition are strongly demanded. Recently, metamaterials present a unique platform for sensing applications owing to their exotic properties. In the current work, a metamaterial sensor for enhanced fingerprint detection of lactose based on resonant coupling of plasmonic modes of split-ring resonators (SRRs) and terahertz characteristic modes of lactose was theoretically and experimentally demonstrated. Large electric field enhancement (about 120 times) at the gap of SRRs allows for the highly sensitive detection. A narrow transmittance peak in the broader transmittance dip which corresponded to the characteristic modes of lactose was observed due to the resonant coupling, and the differential transmittance enhanced as the lactose concentration increased. The experimental result agreed well with the theoretical analysis. Moreover, the selectivity of this SRRs sensor for the target molecule was also verified by using fructose. A low amount of lactose, as small as 20 mg/mL was successfully detected in the experiment. Our study opens a new avenue to exploit new materials or devices for molecule sensing with high sensitivity and selectivity.

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.

Terahertz detection of alcohol using a photonic crystal fiber sensor.

Ethanol is widely used in chemical industrial processes as well as in the food and beverage industry. Therefore, methods of detecting alcohol must be accurate, precise, and reliable. In this content, a novel Zeonex-based photonic crystal fiber (PCF) has been modeled and analyzed for ethanol detection in terahertz frequency range. A finite-element-method-based simulation of the PCF sensor shows a high relative sensitivity of 68.87% with negligible confinement loss of 7.79×10-12 cm-1 at 1 THz frequency and x-polarization mode. Moreover, the core power fraction, birefringence, effective material loss, dispersion, and numerical aperture are also determined in the terahertz frequency range. Owing to the simple fiber structure, existing fabrication methods are feasible. With the outstanding waveguiding properties, the proposed sensor can potentially be used in ethanol detection, as well as polarization-preserving applications of terahertz waves.

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.

An effective approach to quantitative analysis of ternary amino acids in foxtail millet substrate based on terahertz spectroscopy.

Terahertz time-domain spectroscopy has been applied to many fields, however, it still encounters drawbacks in multicomponent mixtures analysis due to serious spectral overlapping. Here, an effective approach to quantitative analysis was proposed, and applied on the determination of the ternary amino acids in foxtail millet substrate. Utilizing three parameters derived from the THz-TDS, the images were constructed and the Tchebichef image moments were used to extract the information of target components. Then the quantitative models were obtained by stepwise regression. The correlation coefficients of leave-one-out cross-validation (Rloo-cv2) were more than 0.9595. As for external test set, the predictive correlation coefficients (Rp2) were more than 0.8026 and the root mean square error of prediction (RMSEp) were less than 1.2601. Compared with the traditional methods (PLS and N-PLS methods), our approach is more accurate, robust and reliable, and can be a potential excellent approach to quantify multicomponent with THz-TDS spectroscopy.

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.

Metamaterial-enhanced vibrational absorption spectroscopy for the detection of protein molecules.

From visible to mid-infrared frequencies, molecular sensing has been a major successful application of plasmonics because of the enormous enhancement of the surface electromagnetic nearfield associated with the induced collective motion of surface free carriers excited by the probe light. However, in the lower-energy terahertz (THz) region, sensing by detecting molecular vibrations is still challenging because of low sensitivity, complicated spectral features, and relatively little accumulated knowledge of molecules. Here, we report the use of a micron-scale thin-slab metamaterial (MM) architecture, which functions as an amplifier for enhancing the absorption signal of the THz vibration of an ultrathin adsorbed layer of large organic molecules. We examined bovine serum albumin (BSA) as a prototype large protein molecule and Rhodamine 6G (Rh6G) and 3,3'-diethylthiatricarbocyanine iodide (DTTCI) as examples of small molecules. Among them, our MM significantly magnified only the signal strength of bulky BSA. On the other hand, DTTCI and Rh6G are inactive, as they lack low-frequency vibrational modes in this frequency region. The results obtained here clearly demonstrate the promise of MM-enhanced absorption spectroscopy in the THz region for detection and structural monitoring of large biomolecules such as proteins or pathogenic enzymes.

Terahertz spectroscopy for bacterial detection: opportunities and challenges.

The demand for advanced bacterial detection tools is continuously increasing, promoted by its significant benefits in various applications. For instance, in the medical field, these tools would facilitate decision making about more tailored therapies once the infection source has been identified. In the past few years, terahertz (THz = 10(12) Hz) spectroscopy has also shown potential as a novel bacterial detection modality due to its unique advantages. Impressive breakthroughs have been achieved in this field related to bacterial component characterization, spore identification, and cell detection. However, some intrinsic limitations and technical bottlenecks have led to some debates about the practicability of its clinical adoption. In this review, we summarize the progress achieved in this field and discuss some challenges and strategies for future implementation of practical applications.

Microfluidic Devices for Terahertz Spectroscopy of Live Cells Toward Lab-on-a-Chip Applications.

THz spectroscopy is an emerging technique for studying the dynamics and interactions of cells and biomolecules, but many practical challenges still remain in experimental studies. We present a prototype of simple and inexpensive cell-trapping microfluidic chip for THz spectroscopic study of live cells. Cells are transported, trapped and concentrated into the THz exposure region by applying an AC bias signal while the chip maintains a steady temperature at 37 °C by resistive heating. We conduct some preliminary experiments on E. coli and T-cell solution and compare the transmission spectra of empty channels, channels filled with aqueous media only, and channels filled with aqueous media with un-concentrated and concentrated cells.

Terahertz spectroscopy of oligonucleotides in aqueous solutions.

A terahertz (THz) spectroscopic study is carried out to analyze DNA mutations in a label-free manner. Three newly designed liquid sample cells are considered and the best is selected as the sample carrier for THz transmission spectroscopic analyses. Discrimination based on spectral signatures of single-base mutations on single-stranded 20 nt oligonucleotides has been shown possible experimentally. The results clearly attest the ability of this promising approach for label-free analyses of single-base mutations of DNA molecules. This study has demonstrated that the THz spectroscopic technology can be considered as a potential diagnostic tool for investigating molecular reactions, such as DNA mutations.

Terahertz spectroscopic identification of explosive and drug simulants concealed by various hiding techniques.

Terahertz time-domain spectroscopy and imaging is used to study the effects of various hiding techniques of spectral features of drug and explosive simulants in combination with different paper and textile barriers. Results show that rapid detection and identification of concealed simulants is possible in the frequency range from 1.5 to 4.0 THz by using an organic-crystal-based terahertz time-domain system and the spectral peak analysis method.

New terahertz dielectric spectroscopy for the study of aqueous solutions.

We present the development of a high precision, tunable far-infrared (terahertz) frequency-domain dielectric spectrometer for studying the dynamics of biomolecules in aqueous solutions in the gigahertz-to-terahertz frequency. As an important benchmark system, we report on the measurements of the absorption and refractive index for liquid water in the frequency range from 5 GHz to 1.12 THz (0.17-37.36 cm(-1) or 0.268-60 mm). The system provides a coherent radiation source with power up to 20 mW in the gigahertz-to-terahertz region. The dynamic range of our instrument reaches 10(12) and the system achieves a spectral resolution of less than 100 Hz. The temperature of samples can be controlled precisely with error bars of ±0.02 °C from 0 °C to 90 °C. Given these attributes, our spectrometer provides unique capabilities for the accurate measurement of even very strongly absorbing materials such as aqueous solutions.