Detection of In Vivo-like Cells by a Biosensor Chip Based on Metamaterials in Terahertz Regime.

Early diagnosis of diseases, especially cancer, is critical for effective treatment. The unique properties of terahertz technology have attracted attention in this field. However, current terahertz bio-detection methods face challenges due to differences between the test environment and the actual in vivo conditions. In this study, a novel method is proposed for detecting in vivo-like cells using a biosensor chip composed of metamaterials and a cavity. The cavity has a thickness of ~50 µm. The structure can protect cells from damage and provides a liquid environment like an in vivo state. Through simulation analysis, the metamaterials sensor exhibits a theoretical sensitivity of 0.287 THz/RIU (Refractive Index Unit) with a 50 µm thick analyte. The detection method is experimentally validated using the apoptosis of glioma cells and various cell types. The biosensor investigates the apoptosis of glioma cells under the impact of temozolomide, and the trend of the results was consistent with the Cell Counting Kit-8 method. Furthermore, at a concentration of ~5200 cells/cm2, the experimental results demonstrate that the sensor can distinguish between neurons and glioma cells with a resonance frequency difference of approximately 30 GHz. This research has significant potential for detecting glioma cells and offers an alternative approach to in vivo-like cell detection.

Investigating the Molecular Rearrangement of Polar Liquid Mixtures Using Terahertz Frequency Domain Reflection Spectroscopy.

A special data processing method for the terahertz frequency domain reflection spectroscopy system has been proposed to analyze the characteristics of a polar mixed liquid. This novel and practical measurement system is characterized by a simpler optical structure and a tunable output frequency range of 0.1-1 THz. By Hilbert transform, stationary wavelet transform, and time domain zero setting method, the reflection coefficient that has been eliminated by the noise and the Fabry-Pérot effect can be obtained by the self-reference calibration method. Then, the dielectric function of the ethanol/n-hexane and propanol/n-hexane mixtures with different mixture ratios can be extracted by this method. In addition, a significant deviation can be observed between the imaginary part of the measured dielectric function and the ideal calculated value. These results indicate that during the mixing process of polar and nonpolar liquids, the hydroxyl functional groups of alcohols significantly change the molecular arrangement pattern of the mixture. The arrangement pattern will result in the formation of the new permanent dipole moment. This study lays a solid foundation for future research on the microscopic mechanism of intermolecular interaction using terahertz frequency domain reflection spectroscopy.

Ultra-sensitive terahertz metamaterials biosensor based on luxuriant gaps structure.

Fast, simple, and label-free detections and distinctions are desirable in cell biology analysis and diagnosis. Here, a biosensor based on terahertz metamaterial has luxuriant gaps, which can excite dipole resonance is designed. Filling the gaps with various analytes can change the biosensor's capacitance resulting in electromagnetic properties changing. The idea is verified by simulations and experiments. The theoretical sensitivity of the biosensor approaches 290 GHz/RIU, and the experimental concentration sensitivity of the biosensor is ≥ 275 kHz mL/cell. Candida Albicans, Escherichia Coli, and Shigella Dysenteriae were selected as analytes, and the measurement frequency shift is 270 GHz, 290 GHz, and 310 GHz, respectively, which indicates that the biosensor can detect and distinguish these bacteria. Successfully detection of low-concentration glioblastoma (200 cells/mL), showing great potential for the early diagnosis of glioblastoma of the biosensor. This biosensor supplies a new horizon for cell detection, which will significantly benefit cell biology investigation.

Research on a high-sensitivity asymmetric metamaterial structure and its application as microwave sensor.

In this paper, an Asymmetric Electric Split-Ring Resonator (AESRR) metamaterial structure is proposed to explore the interaction between metamaterials and electromagnetic waves with the influence of Fano resonance on electromagnetic properties. With the symmetry of basic electric Split-Ring Resonator (eSRR) being broken, a new Fano resonant peak appears at around 11.575 GHz and this peak is very sensitive to the dielectric environment. Based on the proposed high sensitivity of AESRR, a microwave sensor based on a 13 × 13 arrays of AESRR was designed and verified using printed circuit board (PCB) technology. T-shape channel was integrated to the sensor by grooving in the FR-4 substrate which improved the integration and provided the feasibility of liquids detection. Seven organic liquids and four dielectric substrates are measured by this sensor. The measured results show the transmission frequency shifts from 11.575 to 11.150 GHz as the liquid samples permittivity changes from 1 to 7 and the transmission frequency shifts from 11.575 to 8.260 GHz as the solid substrates permittivity changes from 1 to 9. The results have proven the improved sensitivity and the larger frequency shift ∆f on material under test (MUTs) compared with the conventional reported sensor. The relative permittivity of liquid samples and solid samples can be obtained by establishing approximate models in CST, respectively. Two transcendental equations derived from measured results are proposed to predict the relative permittivity of liquid samples and solids samples. The accuracy and reliability of measured results and predicted results are numerically verified by comparing them with literature values. Thus, the proposed sensor has many advantages, such as low-cost, high-sensitivity, high-robustness, and extensive detecting range, which provided a great potential to be implemented in a lab-on-a-chip sensor system in the future.

High-Sensitivity Microwave Sensor for Liquid Characterization Using a Complementary Circular Spiral Resonator.

This paper describes a low-cost, small size, and high-sensitivity microwave sensor using a Complementary Circular Spiral Resonator (CCSR), which operates at around 2.4 GHz, for identifying liquid samples and determining their dielectric constants. The proposed sensor was fabricated and tested to effectively identify different liquids commonly used in daily life and determine the concentrations of various ethanol⁻water mixtures at by measuring the resonant frequency of the CCSR. Using acrylic paint, a square channel was drawn at the most sensitive position of the microwave sensor to ensure accuracy of the experiment. To estimate the dielectric constants of the liquids under test, an approximate model was established using a High-Frequency Simulator Structure (HFSS). The results obtained agree very well with the existing data. Two parabolic equations were calculated and fitted to identify unknown liquids and determine the concentrations of ethanol⁻water mixtures. Thus, our microwave sensor provides a method with high sensitivity and low consumption of material for liquid monitoring and determination, which proves the feasibility and broad prospect of this low-cost system in industrial application.

Reduction/temperature/pH multi-stimuli responsive core cross-linked polypeptide hybrid micelles for triggered and intracellular drug release.

The high toxicity, poor stability, premature drug release, and lack of intracellular stimuli responsibility of current polymeric micelles still hinder them for potential clinical applications. To address these challenges, a novel type of multi-stimuli responsive, core cross-linked polypeptide hybrid micelles (CCMs) was developed for triggered anticancer drug delivery in tumor microenvironment. The CCMs was prepared via free radical copolymerization by using N,N'-methylene-bis-acylamide (BACy) as the cross-linking agent, 2,2-azobisisobutyronitrile (AIBN) as the initiator, where poly (γ-benzyl-L-glutamate) (PBLG) and N-isopropylacrylamide (NIPPAM) as comonomers. The doxorubicin (DOX) was then introduced into the CCMs by hydrazone bond to prepare the drug-incorporated core cross-linked micelles (CCMs-DOX). By the experimental results, the CCMs showed reduction responsibility due to the degradable disulfide bond in the polymer network. The hydrazone bond can be broken under acidic condition causing a controllable drug release for CCMs-DOX. Compared to only 7.7% DOX release under pH 7.4 at 37°C, a much higher DOX release rate up to 85.3% was observed under 10 mM GSH (pH 5.0, 42°C). In vitro cell assays showed that the blank CCMs showed almost no toxicity against HUVEC cells while the CCMS-DOX exhibited significant cancer cell killing effect. These experimental results suggested that the prepared multi-stimuli responsive polymeric micelles could serve as a smart and promising drug delivery candidate for anti-cancer therapy.

[The preparation and study on drug release of a triply-responsive (redox/thermo/pH) cross-linked polymeric micelle as anti-cancer drug carrier].

A multiple-stimuli-responsive drug-conjugated cross-linked micelles was prepared by radical copolymerization. The chemical structure, morphology, and size of the cross-linked micelles were characterized, and the drug loading of the micelle was calculated. The experimental results indicated that the hydrodynamic size of the drug-loaded micelles were about 100 nm, and the as prepared micelles could be degraded and swelled in presence of reducing glutathione (GSH). The low critical solution temperature (LCST) of the micelle was around 39.4℃. According to the experimental results, the micelles will shrink at temperature above the LCST. Subsequently, the accumulative drug release rate was up to 91.78% under acidic (pH 5.0), reductive (GSH 10 mmol/L) and high temperature (42.0℃) conditions mimicking the tumor microenvironment, while a relatively low release rate of 1.12% was observed without stimulation. The drug-conjugated cross-linked micelles showed a strong cell uptake behavior. In the cytotoxicity assay, the micelles exhibited effective anti-cancer activity and excellent biocompatibility. In brief, the experimental results show that the as-prepared drug-conjugated cross-linked micelle exhibits multiple stimuli-responsiveness, which holds great promise for anti-cancer drug delivery.