Weak-value amplified surface plasmon resonance sensor based on joint detection of optical activity and refractive index.

A versatile system combining surface plasmon resonance (SPR) and weak value amplification (WVA) is presented, which can measure the optical activity and refractive index of chiral/achiral molecules, ionic compounds, and their mixture in solution individually or simultaneously. The variations in output light intensity directly exhibit high sensitivity to changes in optical activity and refractive index of the aforementioned substances. Furthermore, by examining the correlation between the intensity variation trend and the optical activity of the chiral molecule, the molecule's absolute configuration can be ascertained. Utilizing this instrument, optical rotation with a resolution of 3.04 × 10-6 rad and refractive index with a resolution of 5.57 × 10-9 RIU were obtained. As an attempt at practical application, this sensor was used to detect the adulteration of glucose and fructose in pure honey. Not only can such compromised honey be distinguished from pure honey using the refractive index or optical rotation, but the difference in optical activity can also be employed to effectively differentiate between adulterated honey samples containing glucose and fructose separately.

Label-free detection and identification of single bacteria via terahertz near-field imaging.

In recent years, terahertz (THz) imaging has attracted much attention because of its ability to obtain physical and chemical information in a label-free, noninvasive and nonionizing manner. However, the low spatial resolution of traditional THz imaging systems and the weak dielectric response of biological samples hinder the application of this technology in the biomedical field. In this paper, we report a new THz near-field imaging method for a single bacteria, through the coupling effect of nanoscale radius of probe and platinum gold substrate, which greatly enhances THz near-field signal of biological samples. A THz super-resolution image of bacteria has been successfully obtained by strictly controlling the relevant test parameters such as tip parameters and driving amplitude. By analyzing and processing the THz spectral image, the morphology and inner structure of bacteria have been observed. The method has been used to detect and identify Escherichia coli represented by Gram-negative bacteria and Staphylococcus aureus represented by Gram-positive bacteria. This application provides a new label-free, noninvasive and nonionizing testing protocol for the detection of single bacteria.

AIEgens/Mitochondria Nanohybrids as Bioactive Microwave Sensitizers for Non-Thermal Microwave Cancer Therapy.

Aggregation-induced emission luminogens (AIEgens) are widely used as photosensitizers for image-guided photodynamic therapy (PDT). Due to the limited penetration depth of light in biological tissues, the treatments of deep-seated tumors by visible-light-sensitized aggregation-induced emission (AIE) photosensitizers are severely hampered. Microwave dynamic therapy attracts much attention because microwave irradiation can penetrate very deep tissues and sensitize the photosensitizers to generate reactive oxygen species (ROS). In this work, a mitochondrial-targeting AIEgen (DCPy) is integrated with living mitochondria to form a bioactive AIE nanohybrid. This nanohybrid can not only generate ROS under microwave irradiation to induce apoptosis of deep-seated cancer cells but also reprogram the metabolism pathway of cancer cells through retrieving oxidative phosphorylation (OXPHOS) instead of glycolysis to enhance the efficiency of microwave dynamic therapy. This work demonstrates an effective strategy to integrate synthetic AIEgens and natural living organelles, which would inspire more researchers to develop advanced bioactive nanohybrids for cancer synergistic therapy.

Terahertz spectroscopic monitoring and analysis of citrus leaf water status under low temperature stress.

Low temperature stress, in the form of chilling and freezing, is one of the major environmental factors impacting on citrus yield, which changes plant's water state and results in the crops' sub-health or injury. The innovative terahertz (THz) spectroscopy and imaging based sensing technology has been shown to be a suitable tool for plant leaf water status determination, due to THz radiation's innate sensitivity to hydrogen bond vibration in aqueous solutions, which is usually related to plant phenotype change. We demonstrate experimentally that the THz absorption coefficient of leaf could be used for distinguishing plant's physiological stress status, exhibiting clear decreasing or increasing trend under chilling or freezing stress respectively. The underlying rationale might be that membrane damage shows a diverse pattern, changing the intra- or extra-cellular liquid environments, likely being linked to the various THz spectral characteristics. There were different adaptations in leaf morphology, leading to different leaf density, which in turn affects the water volume fraction. Moreover, different patterns of the dynamic equilibrium state of free water and bound water under chilling and freezing treatment were revealed by THz spectroscopy. Here, THz spectroscopic monitoring has shown unique potential for judging citrus's low temperature stress state through bio-water detection and discrimination.

Walk-through millimeter wave imaging testbed based on double multistatic cross arrays.

A walk-through millimeter wave imaging testbed using double multistatic cross arrays is presented. The imaging testbed consists of a vector network analyzer, a power amplifier, a low-noise amplifier, 36 SP6T electrical switchers, and double homemade multistatic cross arrays placed on both sides of the imaging area. The imaging algorithm based on the range migration algorithm is deduced, and the imaging performance is analyzed. The metallic ball experimental results show that the imaging resolution is close to the theoretical value, and demonstrate the imaging feasibility of the testbed working in mutual mode.

Deep learning aided quantitative analysis of anti-tuberculosis fixed-dose combinatorial formulation by terahertz spectroscopy.

Anti-tuberculosis fixed-dose combinatorial formulation (FDCs) is an effective drug for the treatment of tuberculosis. As a compound medicine, its efficacy is based on the comprehensive action of multiple main ingredients. If the content of an active ingredient is insufficient, not only will it reduce the curative effect, but it also causes patients to develop drug resistance and leads to the evolution of drug-resistant strains of tuberculosis, which hamper the treatment of the disease. Thus accurate detection of the contents of active components in the anti-tuberculosis FDC is the key link of its quality control. For the first time, convolutional neural networks (CNN), one of the most popular deep learning methods, is adopted to develop a quantitative calibration model based on terahertz time-domain spectroscopy (THz-TDS) for the accurate detection of the content of each active component in the anti-tuberculosis FDCs. For comparison with CNN, partial least squares regression (PLSR) was also introduced to build a reference quantitative calibration model. For CNN modeling, the raw THz spectral is fed to the model directly; While for PLSR, prior to the spectrum feeding to the model, the raw spectral data are processed by multiple different combinations of preprocessing. Experimental and simulation results demonstrate that although preprocessing techniques can improve the prediction performance of PLSR, its prediction capabilities is still inferior to CNN based on raw spectrum. Therefore, for the quantitative analysis of the content of each active component in the anti-tuberculosis FDCs, CNN appears to be an ideal modeling method.

Aperture-type terahertz near-field imaging with a cylindrical frustum-shaped plastic probe.

We designed an aluminum-coated plastic probe made from the combination of cylinder and a frustum of a cone for terahertz near-field imaging. The bunching width of the probe is 12 µm and the electric field intensity enhancement factor just outside the probe tip reaches up to 25. An imaging resolution obtained through near-field imaging experiments on a variety of targets, including narrow metals and narrow media, is 6 µm (λ/450) at 0.11 THz. By adopting an adaptive threshold segmentation image processing algorithm that combines Hilbert scanning and wavelet transform, the influence of a large area of metal near the imaging area on the imaging result is successfully suppressed. Imaging of a scratch on the plastic substrate makes the new probe feasible for quality identification of nonmetallic cultural relics.

Low terahertz-band scanning near-field microscope with 155-nm resolution.

We report on the design and implementation of a scattering-type scanning near-field microscope working in the low terahertz-band under ambient conditions for nanoscopic investigations of physical properties and characteristics at sample surfaces and interfaces in the microwave and millimeter wave bands. Employing a nano-tip that oscillates vertically at a frequency Ω as the antenna, and a subharmonic mixer as the receiver, and corresponding demodulation algorithms, the back-scattered light carrying tip-sample interaction information is effectively extracted, while excluding almost all of the background noises. The amplitude and phase images constructed from signals demodulated at various harmonics (nΩ, n = 1 - 4) are obtained while scanning an Au-Si step structure with the newly developed microscope, and a resolution of 155 nm (~λ/20,000) has been demonstrated at the fourth harmonic frequency (4Ω) working at 110 GHz, with signal-to-noise ratio (SNR) equal to 44.4 dB on the Au surface and 36.2 dB on the Si surface, demonstrating the power of this new instrument for micro/nano-resolution studies in the millimeter wave band.

A solid-state nanopore-based single-molecule approach for label-free characterization of plant polysaccharides.

Polysaccharides are important biomacromolecules existing in all plants, most of which are integrated into a fibrillar structure called the cell wall. In the absence of an effective methodology for polysaccharide analysis that arises from compositional heterogeneity and structural flexibility, our knowledge of cell wall architecture and function is greatly constrained. Here, we develop a single-molecule approach for identifying plant polysaccharides with acetylated modification levels. We designed a solid-state nanopore sensor supported by a free-standing SiN x membrane in fluidic cells. This device was able to detect cell wall polysaccharide xylans at concentrations as low as 5 ng/µL and discriminate xylans with hyperacetylated and unacetylated modifications. We further demonstrated the capability of this method in distinguishing arabinoxylan and glucuronoxylan in monocot and dicot plants. Combining the data for categorizing polysaccharide mixtures, our study establishes a single-molecule platform for polysaccharide analysis, opening a new avenue for understanding cell wall structures, and expanding polysaccharide applications.

Near-Field Nanoscopic Terahertz Imaging of Single Proteins.

Terahertz (THz) biological imaging has attracted intense attention due to its capability of acquiring physicochemical information in a label-free, noninvasive, and nonionizing manner. However, extending THz imaging to the single-molecule level remains a challenge, partly due to the weak THz reflectivity of biomolecules with low dielectric constants. Here, the development of graphene-mediated THz scattering-type scanning near-field optical microscope for direct imaging of single proteins is reported. Importantly, it is found that a graphene substrate with high THz reflectivity and atomic flatness can provide high THz contrast against the protein molecules. In addition, a platinum probe with an optimized shaft length is found enabling the enhancement of the amplitude of the scattered THz near-field signals. By coupling these effects, the topographical and THz scattering images of individual immunoglobulin G (IgG) and ferritin molecules with the size of a few nanometers are obtained, simultaneously. The demonstrated strategy thus opens new routes to imaging single biomolecules with THz.

Detection of gene mutation responsible for Huntington's disease by terahertz attenuated total reflection microfluidic spectroscopy.

Terahertz absorption spectroscopy based on attenuated total reflection (ATR) from a microfluidic sample cell was designed and implemented to detect gene mutations leading to Huntington's disease (HD). The self-developed compact ATR microfluidic system was employed to detect two groups of base-repeated DNA molecules combined with a terahertz time-domain spectrometer in a marker-free manner. The first group featured different repetition patterns of oligonucleotide fragments, and the second group included the HD gene. For the oligonucleotides of different repetition patterns, there were significant differences among the three oligonucleotides with three repeats of the double bases, which could be unambiguously classified and identified; For the HD gene, it was found that the magnitude of the terahertz absorption coefficients of the four oligonucleotide solutions was, in ascending order, CAG-4 < CAG-16 < CAG-32 < CAG-40 (the numbers are the repeat times of the CAG base segment, with 40 repeats belonging to the HD gene), when the concentration of oligonucleotide was 1 mg/mL. Principal component analysis result indicated that the spectral differences of the four oligonucleotide solutions with different CAG repeat times were statistically significant and clearly distinguishable. These results demonstrate the potential of terahertz spectroscopy as a noninvasive, unmarked, fast and low-cost assay for gene diagnosis and clinical disease detection.

Terahertz detection of porosity and porous microstructure in pharmaceutical tablets: A review.

Pores are inevitably produced during the production of pharmaceutical tablets, which greatly affects a range of tablet properties such as hardness, friability, tensile strength, disintegration, dissolution, and ultimately the bioavailability of an orally administered tablet. The pursuit of speed and non-destructiveness in detection of pores in pharmaceutical tablets has recently ushered in the use of terahertz (THz) techniques. This review briefly introduces the mechanism of the formation of the pores in tablets and the traditional methods of detecting them. The main focus is the relevant research work of THz technology applied to the detection of the pores in tablets, including the quantitative detection of porosity and analysis of porous microstructure. It also discusses the challenges and the future development directions of THz technology in the detection of pores in tablets.

Detection of single-base mutation of DNA oligonucleotides with different lengths by terahertz attenuated total reflection microfluidic cell.

Many human genetic diseases are caused by single-base mutation in the gene sequence. Since DNA molecules with single-base mutation are extremely difficult to differentiate, existing detection methods are invariably complex and time-consuming. We propose a new label-free and fast terahertz (THz) spectroscopic technique based on a home-made terahertz attenuated total reflection (ATR) microfluidic cell and a terahertz time-domain spectroscopy (THz-TDS) system to detect single-base-mutated DNA molecules. The detected object DNA molecules are normal hemoglobin gene, sickle cell anemia gene (15 nt), JAK2 gene wild type and JAK2 V617F gene mutation (39 nt) from sickle cell anemia and thrombocytopenia, respectively. Results show that the oligonucleotide fragments with single-base mutation can be identified by THz spectroscopy combined with the ATR microfluidic cell, and the recognition effect of short oligonucleotide fragments with single-base mutation is better than that of long oligonucleotide fragments. The terahertz biosensor is shown to have high sensitivity and can be used to detect DNA molecules directly in the solution environment.

Low-frequency fiber optic hydrophone based on weak value amplification.

A high-sensitivity low-frequency fiber optic hydrophone based on weak value amplification (WVA) is proposed and demonstrated. A polarization maintaining (PM) fiber with a length of 0.8 m wound around a polycarbonate (PC) tube is used as the sensing element. Theoretical analysis shows that the PM fiber in a WVA measurement scheme responds to underwater acoustic pressure with unprecedented sensitivity. The prototypical hydrophone based on such a scheme can sense underwater acoustic disturbance as weak as 1.3×10-6 Pa/Hz1/2 at 10 Hz, with a flat frequency response in the low-frequency band of 0.1-50 Hz. The experimental result agrees well with the theoretical prediction to within 0.5 dB.

Measurement of Chiral Molecular Parameters Based on a Combination of Surface Plasmon Resonance and Weak Value Amplification.

A novel combination of surface plasmon resonance (SPR) and weak value amplification (WVA) is employed to measure the optical rotation angle and refractive index of chiral enantiomers such as sugars and amino acids. An extremely low optical rotation change (2.73 × 10-4 rad) is readily measurable, with a resolution of 6.75 × 10-7 rad, 1 order of magnitude higher than that obtained using weak value amplification with intensity modulation, and a refractive index change of 1.13 × 10-6 RIU is also detected, with a resolution of 1.99 × 10-9 RIU, a nearly 1-order-of-magnitude increase in sensitivity over weak measurement based on a Mach-Zehnder interferometer. The optical activity and refractive index changes of chiral molecules are determined in real time by measurements of the output light intensity variation, whereby the absolute configuration of the chiral molecule is identified through the relation between intensity and molecular orientation. The SPR-WVA combination sensing scheme fills the gap of capability for detecting the optical activity of a molecular solution, which has not been possible with conventional SPR alone.

Fiber optic interferometric seismometer with phase feedback control.

A high-sensitivity ultralow-frequency fiber optic interferometric seismometer using phase feedback control is proposed and demonstrated. The principle of sensitivity improvement using feedback is described, and the characteristics of the seismometer, including the ultralow-frequency vibration sensing with Michelson interferometer with and without feedback control, are analyzed in terms of the amplitude response and phase response. The phase feedback control loop is designed and implemented, and higher sensitivity for very low frequency vibration is achieved. The efficacy of the new approach is demonstrated experimentally, showing that the weak vibration signal originally buried in noise can be observed unambiguously.

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.

Vibrational spectra of pyrazinamide and isoniazid studied by terahertz spectroscopy and density functional theory.

Pyrazinamide and isoniazid, as two first-line anti-tuberculosis drugs, are investigated by terahertz time-domain spectroscopy (THz-TDS). Both pyrazinamide and isoniazid have three absorption peaks, at 0.50, 0.71, 1.42 THz and 1.16, 1.46, 1.56 THz, respectively, which can be used as the basis for qualitative identification of these two drugs. In order to gain insight into the origin of the characteristic absorption peaks, density functional theory (DFT) based on single molecular, dimer, and crystalline structures of pyrazinamide and isoniazid are performed. The purpose of the calculation based on the single molecular structure is to understand the intramolecular interaction, while those based on the dimer and crystalline structures are to investigate the intermolecular interactions in PNZ and INZ. Comparing the theoretical results of the dimer and crystalline based structures reveals that the crystalline structure leads to vibrational spectra that are closer to the experimental values in terms of the number of absorption peaks and the positions of the absorption peaks. Vibrational mode assignments can be summarized as that the characteristic absorption peaks of pyrazinamide mainly come from intermolecular interaction, and the characteristic absorption peaks of isoniazid originate from both the intramolecular and intermolecular interactions. Our experimental and theoretical results indicate that the combination of THz-TDS with DFT is an effective approach for identification of molecules with pharmaceutical significance.

Photovoltaic Effect Related to Methylammonium Cation Orientation and Carrier Transport Properties in High-Performance Perovskite Solar Cells.

Solar cells based on organic-inorganic hybrid halide perovskites (OIHHPs) have been widely studied because of their increasing power conversion efficiency. Extensive research has been conducted in electrical and optical properties and device fabrication. However, in terms of material science, the photovoltaic effects of OIHHP are still not well understood. Here, we theoretically investigate the photovoltaic phenomena of MAPbI3 (MA = CH3NH3+) under standard AM 1.5G sunlight illumination, considering the MA cation orientation, light incident angle, polarization, and photon energy, using Keldysh nonequilibrium Green's function formalism combined with density functional theory calculations. It is found that the short-circuit current density Jsc has a maximum value of 383.149 A/m2 when the MA orientation is parallel to the transport direction, whereas it is negligible when the MA orientation is orthogonal to the transport direction. In addition, full consideration is also given to the direction of incidence of sunlight and its polarization state. Nevertheless, of all factors considered, MA orientation plays the decisive role, for Jsc still has a respectable value of 364.112 A/m2 even for a 90° sunlight incident angle relative to the transport direction, so long as the MAs are aligned in the transport direction. The increase in the photocurrent is attributed to an increase in the transmission coefficient of low-energy holes, as well as improvement of the velocities and mobilities of electrons and holes in the MAPbI3-based device with [001] MA orientation. The results suggest that during the designing of high-performance OIHHP-based solar cells and photoelectronic devices, the crystal orientation and MA cation orientation relative to the transport direction should be carefully considered as they directly affect carrier transport properties.

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.