Shihan Yan

Terahertz Biosensing Based on a Polarization-Insensitive Metamaterial

A polarization-insensitive metamaterial biosensor composed of metallic square ring resonators is proposed and is shown to be especially suitable to work together with the linear polarized femtosecond laser pumped terahertz time-domain spectroscopy. A symmetric slit is distributed on every side of the ring to render the biosensor insensitive to the polarization direction of the incident terahertz wave. The proposed structure is analyzed with the finite-element method and investigated experimentally. The results reveal that a minimal resolution of 17.7 μmol/L in the detection of bovine serum albumin is obtained when the biosensor is oriented arbitrarily in the plane containing the electric field vector.

Rapid and label-free detection and assessment of bacteria by terahertz time-domain spectroscopy

Here we demonstrated the potential and applicability of terahertz (THz) spectroscopy to detect four commonly found bacteria in the infectious diseases. Besides the different spectral characteristics between bacterial species, THz absorption differences for living bacteria, dead bacteria and bacterial powder of the same species were also investigated. Our results revealed that small differences in water contents between bacterial cells account for distinct discrepancies of the absorption coefficients, which can be used for bacterial species identification. Furthermore, living and dead bacteria showed different absorption coefficients as a result of their different hydration levels, suggesting that THz spectroscopy can be used to rapidly assess the living state of bacteria under test. Our results clearly demonstrated the ability of THz spectroscopy for time-saving and label-free detection of bacteria with minimal sample preparation, potentially to be utilized for point-of-care tests in the near future. Schematic representation of bacterial detection by THz spectroscopy. Different bacteria have distinctive absorption coefficients as a result of their different water contents.

Determination of Critical Micelle Concentrations of Surfactants by Terahertz Time-Domain Spectroscopy

A novel detection method is presented to determine the critical micelle concentrations (CMCs) of surfactants by using a simple and convenient terahertz time-domain spectroscopy (THz-TDS) technology which has been successfully used to study the picosecond dynamics of water in reverse micelles. Absorption coefficients or refractive indices of aqueous solutions of an ionic surfactant sodium dodecyl sulfate and a nonionic surfactant nonaethylene glycol monododecyl ether in 0.2-1.8 THz frequency range at different concentrations are measured through the THz-TDS. A clear intersection of THz absorption coefficient or refractive index caused by the micelle formation is observed. This phenomenon is strongly associated with the change of component ratio between surfactant, bulk water and hydration water during the formation of micelles. The corresponding concentration is determined as the CMC of the surfactant which is in good agreement with the most existing results using traditional methods. For comparison, absorption coefficients of the two surfactants in hydrochloric acid solutions are also measured and differences in contrast to those in aqueous solutions are observed and explained. Our findings indicate that THz spectroscopy technology can be applied to determine the CMCs of surfactants in a sensitive, accurate, and label-free way.

Label-free detection of anti-estrogen receptor alpha and its binding with estrogen receptor peptide alpha by terahertz spectroscopy

Terahertz (THz) spectroscopic techniques were employed to study the hydration shell formation around anti-estrogen receptor alpha (AER-α), an important biomarker in breast cancer diagnosis, and to detect the binding reaction between AER-α and estrogen receptor peptide alpha (ERP-α), in aqueous solutions. A remarkable nonlinear relation between THz absorption and AER-α concentration was demonstrated, shedding some light on the formation process of the hydration shell around AER-α. THz spectroscopic properties of the AER-α were also shown to be significantly affected by the binding with the ERP-α, to the extent that THz transmission and attenuation could be used to investigate the dielectric properties of antibody–antigen binding reactions.

Label-free sensing of the binding state of MUC1 peptide and anti-MUC1 aptamer solution in fluidic chip by terahertz spectroscopy

The aptamer and target molecule binding reaction has been widely applied for construction of aptasensors, most of which are labeled methods. In contrast, terahertz technology proves to be a label-free sensing tool for biomedical applications. We utilize terahertz absorption spectroscopy and molecular dynamics simulation to investigate the variation of binding-induced collective vibration of hydrogen bond network in a mixed solution of MUC1 peptide and anti-MUC1 aptamer. The results show that binding-induced alterations of hydrogen bond numbers could be sensitively reflected by the variation of terahertz absorption coefficients of the mixed solution in a customized fluidic chip. The minimal detectable concentration is determined as 1 pmol/μL, which is approximately equal to the optimal immobilized concentration of aptasensors.

Terahertz biosensing of protein based on a metamaterial

Proteins perform a vast array of functions within living organisms and the realization of its function is derived from the interaction with other molecules. Research about protein-protein interaction empower the current knowledge on biochemical cascades, metabolic process and disease pathogenesis. So far, there are multitudes of methods invented to investigate whether different kinds of proteins interact with each other. To achieve sufficient sensitivity and specificity, those approaches usually extend over a couple of days and a series of steps. Here we demonstrate that metamaterials operating in the terahertz frequency range show promising potential for fabricating the highly sensitive and selective bio-macromolecule sensors. Experimental results reveal that the rat IgG and corresponding anti-rat IgG mixed solution bring in a larger resonance shift in THz transmission spectra than the non-interacting protein mixture solution, rat IgG and BSA. The method and the achieved results demonstrate the capacity and usefulness of terahertz spectroscopy in bio sensing of interacting proteins.

Sheet conductance and imaging of graphene by terahertz time-domain spectroscopy

A rapid, nondestructive and high-through quality characterization of large-area graphene films is presented based on the Terahertz (THz) time-domain spectroscopy technology. Sheet conductance of graphene films was obtained from the THz transmission measurement and the data analysis was based on the Fresnel coefficient and the Tinkham film equation. In comparison to the traditional four-point probes method, the measurement result showed a quite good consistency. Conductance imaging of graphene by THz method was performed and used to estimate the quality of graphene films on the Si substrate.

The properties, preparation approaches and uses of microfluidic channels for terahertz absorption signatures detection in aqueous

A microfluidic channels chip and its processing method and application are introduced for Terahertz (THz) absorption signatures detection of biomolecules in aqueous solution. Thousands of rectangular microchannels with a characteristic dimension of 2 μm and their reservoirs were precisely etched in a high resistivity silicon wafer by lithography and etching process, then the silicon wafer and a glass sheet were bonded to form a sealed microfluidic chip by anodic bonding technology. The chip can be sampled through the capillary action and the microfluidic pressure system. Three absorption signatures around 850, 928, 950 GHz of dissolved λ-DNA were obtained in 0.7∼1.0 THz band by using this chip and the coherent photomixing spectrometer. It is indicated that dispersion of biomolecular solution in 2 μm spaces between the tines of the grating in microchannels can reduce the water component in THz transmission detection, thereby reducing the water background absorption, effectively improve the signal strength of THz characteristic attenuation.

Detection of oligonucleotides in aqueous solution based on terahertz spectroscopy

A terahertz spectroscopic study is carried out to analyze DNA mutations in a label-free manner. The 5 base mutations from the 3′-terminus on single-stranded 17nt oligonucleotides has been detected in aqueous solution.

Label-free protein detection using terahertz time-domain spectroscopy

In the proposed method the membrane made of nitrocellulose after being moved on proteins is directly scanned by using terahertz time domain spectroscopy system (THz-TDS) to qualitatively and quantitatively protein species and quantity.