Terahertz spectroscopy, with the advantages of label-free and non-ionizing has been considered as a potential method for biomolecule detection. Hereby we present a promising approach for the label-free protein sensing in liquid environment. In this work, we designed a grapheme-based device to increase the accumulated amount of protein molecules in the solution. The sensor demonstrates a quick and sensitive response to HER2 proteins and gave a linearly response to the concentrations of HER2 from 63 ng/ml to 4.0 μg/mL. The results demonstrated that once HER2 molecules targeting on the surface of graphene, the conductivity of graphene was significantly changed. This provided us a potential method to detect trace biomarker within liquid phase by using terahertz spectroscopy.
Here, we proposed the thin-film total internal reflection geometry (TF-TIR) for sensitive material characterization. Equations to extract the material dielectric constant in the TF-TIR geometry was derived. The TF-TIR technique consumes less sample material and provides higher sensitivity compared with the traditional attenuated total reflection (ATR) geometry. The sensitivity of TF-TIR geometry was first investigated by simulation using a 10 μm thick α-lactose thin film as the sample. A THz microfluidic device was fabricated according to the TF-TIR design in the simulation with TOPAS and high-resistivity Si as the top and bottom plate, respectively. The reaction chamber was sandwiched between the TOPAS and Si plates. The device was placed on a right-angle Si prism to realize the total internal reflection. Water and alcohol mixtures were used to verify the sensitivity of the device. Our results demonstrate that the TF-TIR technique has the potential to improve the sensitivity in measuring the dielectric constant of biological samples with THz waves. Our design can be used for THz lab-on-chip devices.
As a new two-dimensional material, MoS2 has been extensively studied in terahertz modulation due to its excellent photoelectric properties. Herein, we studied a novel method for label-free detection of the carcinoembryonic antibody based on MoS2 nanosheets using terahertz spectroscopy. Protein molecules were fabricated on the COC substrates with MoS2 nanosheets. A self-made simple sample cell was used to get signal of protein molecules in a liquid phase. Computational analysis was performed using a classic sandwich structure model. The refractive index and absorption coefficient were calculated. As a result, the THz signal increased with the protein concentration increasing in 0.2-1.1THz. The cole-cole plot was also investigated. The effectiveness of MoS2 nanosheets for adsorbing protein molecules has been demonstrated, which can be used to detect carcinoembryonic antigen sensitively in the future.
The use of terahertz radiation in various fields such as biology and medicine is increasing every year. Meanwhile, people are increasingly concerned about the mechanism on the interaction between terahertz radiation and biological system. In this study, we evaluated the effect of the cellular response of bEnd.3 which exposing to the terahertz radiation in the range of 0.1-3.5 THz. We collected the spectral data of cells during the irradiation with a temperature of 20.6°C and a relative humidity of 5%. Meanwhile, the apoptosis of cell was assessed by Annexin V-FITC/PI kit. As a result, the apoptosis of cells were inhibited from 0 and 6 hours after terahertz irradiation and promoted at 12 hours after irradiation. Moreover, we also calculated the complex dielectric constant of bEnd.3 cells at different exposures. The results demonstrate that the dielectric loss of cells showed a slight decrease with the increase of exposure in the range of 0.2-1.4 THz.
Terahertz (THz) spectroscopy is sensitive to probe several aspects of biological systems. In THz frequency, electrically controllable Drude-like intraband absorption makes graphene a promising platform for building graphene-based optoelectronic devices such as THz biosensor. In this work, BSA protein thin films were spin-coated and incubated on single-layer graphene. IR lasers with different power were used as the pump light to stimulate the sandwich-like sample respectively. The graphene monolayer complex conductivity was calculated using the transmission method. The novel optical properties of single-layer graphene and BSA protein on graphene in the THz range will be discussed in this paper.
Hemagglutinin (HA) is the main surface glycoprotein of the influenza A virus. The H9N2 subtype influenza A virus is recognized as the most possible pandemic strain as it has crossed the species barrier, infecting swine and humans. We use terahertz spectroscopy to study the hydration shell formation around H9 subtype influenza A virus’s HA protein (H9 HA) as well as the detection of antigen binding of H9 HA with the broadly neutralizing monoclonal antibody. We observe a remarkable concentration dependent nonlinear response of the H9 HA, which reveals the formation process of the hydration shell around H9 HA molecules. Furthermore, we show that terahertz dielectric properties of the H9 HA are strongly affected by the presence of the monoclonal antibody F10 and that the terahertz dielectric loss tangent can be used to detect the antibody binding at lower concentrations than the standard ELISA test.
Terahertz spectroscopy is sensitive to probe several aspects of biological systems. We have reported the terahertz dielectric spectrum is able to identify the type of the charges in the hydrogen-bonded antibodies’ networks in our previous work. Recently we demonstrate a highly sensitive THz-TDS method to monitor binding interaction of influenza hemagglutinin (HA) against its target antibody F10. The terahertz dielectric properties of HA was strongly affected by the presence of a specific antibody. Protein solution concentration or even molecular binding interaction can also affect the terahertz signal. This enables us to detect the specificity and sensitivity of antibody-antigen binding under THz radiation.
Terahertz spectroscopy is able to probe several aspects of biological systems. Most well known is its sensitivity to water
due to the strong water absorptions at terahertz frequencies. However an increasing number of studies have shown that
it is not just water content that terahertz is sensitive to and that other factors such as tissue structure, molecular
arrangement or even temperature can also affect the signal. Examples ranging from breast cancer spectroscopy to
antibody protein spectroscopy will be presented and discussed.
We demonstrate how the terahertz properties of porcine adipose tissue and skeletal muscle are affected by formalin fixing. Terahertz radiation is sensitive to covalently cross-linked proteins and can be used to probe unique spectroscopic signatures. We study in detail the changes arising from different fixation times and see that formalin fixing reduces the refractive index and the absorption coefficient of the samples in the terahertz regime. These fundamental properties affect the time-domain terahertz response of the samples and determine the level of image contrast that can be achieved.
In this paper, we measured and analyzed the characteristic of endogenous fluorophores in porcine layered retina by using
advanced fluorescence spectroscopy and microscopy imaging technology. It was found that there were obvious contrasts
corresponding to the different layers of retina, which may be important for fundus disease diagnosis. The retinal pigment
epithelium cells exhibited strong autofluorescence with as emission peak of 600±10nm when excited with 860-nm light.
The emission peak of photoreceptors was at 652±5nm, and the emission peak of retinal vessels layer was weak and at
640~700nm, when excited with 488-nm light. Autofluorescence images of three layers of retina were obtained using the
same setup. We concluded that the main endogenous fluorophore in PRE was lipofuscin and that in retinal vessels was
porphyrin. What's more, the FMHW (full width at half. maximum) of retinal fluorescence spectrum was broad, which
suggested that there wasn't only one endogenous fluorophores of tissues excited.
Transplantation technique of retinal pigment epithelium has been noticeable in recent years and gradually put into
clinical practice in treatment of retinal degenerative diseases. Generally, immunological, histochemical, and physical
methods are used to study the iris pigment epithelium (IPE) and retinal pigment epithelium (RPE) cells, which need
complex sample preparation. In this paper, we provided a simple autofluorescence microscopy to investigate the fresh
porcine IPE and RPE cells without any pretreatment. The results showed that the morphology and size of both were
similar, round and about 15 μm. The main flourophore in both cells was similar, i.e. lipofuscin. In additional, the
autofluorescence spectrum of RPE shifted blue after light-induced damage by laser illuminating. Because it was easier
for IPE to be damaged by laser than for RPE, and the power of one scanning operation to get a full image was strong
enough to damage IPE sample, we hadn't get any satisfied autofluorescence spectrum of IPE.
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