Terahertz biophysics
人类对疾病的恐惧、对健康的渴望、对永葆青春的向往和对返老还童的想象都可能成为驱动科学与技术创新的内驱力. 激光的发明、显微技术的发展和蛋白质结构的解析等, 诞生了许多诺贝尔奖. 物理与生物的交叉融合不仅让人类用物理的手段解决生物问题, 而且生命科学的发展需求也推动了物理学的发展. 然而, 在电磁波谱上, 还有一个至今没有被人们完全认识的频段—太赫兹电磁波, 因其长期受限于电子学和光子学技术扩展的瓶颈, 至今未能服务于人民生命健康. 同时太赫兹信息神经系统的产生、探测以及太赫兹波对生物组织的作用规律都需要进一步探索.
尽管太赫兹科学与技术已发展近半个世纪, 由于太赫兹波源的缺乏, 太赫兹电磁波与物质相互作用, 尤其是与生物物质相互作用的研究一直止步在弱场线性相互作用层面. 在弱场区间, 人们正在利用太赫兹谱学成像技术研究生物物质的光谱特征, 正尝试将其应用于新冠检测、肿瘤筛查、物质鉴别等. 近年来, 随着大型同步辐射光源、自由电子激光、高频率真空电子器件、半导体器件以及超快超强高能激光技术的快速发展, 为太赫兹电磁波源技术带来了前所未有的进步, 各种大功率太赫兹波源已相继问世. 人们在DNA、蛋白、水等最基本生命物质中观察到了太赫兹场诱导的电磁生物效应, 并在分子层面、细胞层面、组织层面、个体层面都看到一些太赫兹诱导的非热生物学现象, 例如利用强场太赫兹激光作为“电磁剪刀”对基因进行无剪切酶参与的基因编辑、神经细胞中太赫兹信息的产生和传输以及太赫兹对神经系统的刺激作用方面的研究成果也已经被报道. 这些激动人心的结果展示了太赫兹生物物理服务于人民生命健康的潜力.
“中国生物物理学会·太赫兹生物物理分会”于2020年11月批准成立, 并于2021年在天津召开全国太赫兹生物物理年会. 基于本次大会, 在国防科技创新研究院常超教授的提议下, 我们邀请了国内若干位活跃于太赫兹生物物理研究前沿的中青年学者撰文, 对近年来该领域部分热点进行总结回顾. 其中既包括对太赫兹生物学效应、太赫兹生物化学传感检测、太赫兹无线通信等的综述, 也包括太赫兹近场显微镜技术、分子动力学模拟、水合物太赫兹调控、太赫兹辐射源等方面的研究论文. 受水平及时间所限, 本专题所反映的太赫兹生物物理研究现状难免挂一漏万, 不当之处恳请各位同仁批评指正. 希望本专题能对国内太赫兹生物物理研究的学术交流做一点贡献.
2021, 70 (12): 128201.
doi: 10.7498/aps.70.20210647
Abstract +
Recovering the protein activity of p53 mutants through small molecule ligand binding (eg. arsenic) is an important strategy for tumor suppressor therapy. However, the mechanistic basis on the changes of collective dynamics and their roles of p53 protein in functional recovery process has not been fully elucidated. Herein, the normal mode calculations based on all-atom elastic network model are employed to characterize the terahertz low frequency motions of core DNA-binding domain (p53C) which is essential for p53 protein activities in transcriptional transactivation. We find that the lowest-frequency collective vibration mode of the p53C mutant is effectively restored by the binding of arsenic (III) ligand. In R249S mutant, the L1 loop is stabilized through restricting the swing-out movement. The results obtained from atomic backbone fluctuations suggest that the arsenic binding can significantly improve the L1 loop and L2 loop fluctuations. The statistical analysis of low frequency vibration mode reflects that the arsenic-bound R249S mutant has an apparent recovery of frequency shift in the terahertz range. The residue-residue motion correlation also suggests that structural components binding to arsenic are dynamically coupled. In the H2 helix with arsenic-binding residues, the motions of C124, C135, M133 and C141, are correlated with the arsenic recovery. These results provide the terahertz biophysical mechanism for the recovery effect of arsenic (III) on the p53 protein activity and new evidence for the coupling of the low-frequency vibration characteristics of protein structures with its function, thus giving a new physical insight into the p53 related cancer therapies.
2021, 70 (24): 248703.
doi: 10.7498/aps.70.20211715
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Terahertz scattering scanning near-field optical microscopy (s-SNOM), as an important means to break through the limits of conventional optical diffraction, can achieve super-resolution imaging on a nanoscale and has a wide range of applications in biological nano-imaging, terahertz nano-spectroscopy, nanomaterials imaging, and the study of polarized excitations. As an important component of the terahertz s-SNOM, the atomic force microscope tip plays a key role in implementing the near-field excitation, detection, and enhancement. However, the tip-sample interaction can greatly affect the results. In this paper, the effects of tip-sample interaction on near-field excitation, near-field detection, and terahertz near-field spectrum in terahertz s-SNOM are revealed through simulations and experiments. First, the wave vector coupling weight of the near field excited by the tip is investigated, and it is found that the wave vector is concentrated mainly on the order of 105 cm–1, which differs from that of the general terahertz excitations by 2 to 3 orders of magnitude, indicating that the terahertz near field is difficult to excite terahertz excitations. Secondly, through theoretical and experimental studies, it is found that the metal tip interferes with the surface near-field of the graphene disk structure, which indicates the limitations of the terahertz s-SNOM in probing the near-field distribution of the structure. Finally, the influence of the tip on the near-field spectrum is studied. It is found that the tip length and cantilever length are important parameters affecting the near-field spectrum, and the influence of the tip on the near-field spectrum can be reduced by increasing the tip length or cantilever length.
2021, 70 (24): 248704.
doi: 10.7498/aps.70.20211210
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A GaAs photoconductive antenna is one of the important radiation sources of terahertz electromagnetic waves. Antenna arrays can increase the radiation intensity of terahertz waves. Therefore, photoconductive antennas and arrays have attracted much attention for a long time. In this study, CST Microwave Studio is used to conduct a simulation calculation of the characteristics of a photoconductive antenna array radiating terahertz electromagnetic waves. Using the current transient model, the pulsed photocurrents generated when the laser is incident on the GaAs photoconductive antenna are calculated. With the pulsed photocurrents serving as an excitation source, a simulation calculation of the radiation performance of photoconductive antenna is conducted, and the effects of antenna structure and substrate material on the radiation of terahertz waves are analyzed. Based on this, the far-field radiation of terahertz wave radiated by the GaAs photoconductive antenna array is calculated. The simulation results show that the photoconductive antenna array radiates terahertz waves with stronger directivity. The width of main lobe is reduced, and its far-field radiation conforms to the multiple relationships of electric field superposition. A 1 × 2 GaAs photoconductive antenna array is developed, and the experimental results are consistent with the simulation conclusions, thereby laying a theoretical and experimental basis for fabricating the multielement terahertz photoconductive antenna arrays.
2021, 70 (24): 243202.
doi: 10.7498/aps.70.20211716
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Water has the strong absorption of terahertz (THz) wave, so it always a difficult problem to study the characteristics of aqueous samples by THz technology. In this paper, THz waves with high field strength are obtained at the position of sample by using photoconductive antenna working in high-gain mode and horn shaped graded parallel plate waveguide in THz time-domain spectrum system, and the THz spectrum of α-lactose solution in a range of 0.1－1.5 THz is directly detected. Furthermore, the absorption spectrum of α-lactose single molecule model in water environment is simulated by the density functional theory, and the simulation results are in good agreement with the experimental results. This work has important reference value for directly detecting the spectral characteristics of water samples in THz band.
2021, 70 (24): 248702.
doi: 10.7498/aps.70.20211731
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Water is the source of all life. The understanding of the terahertz absorption spectrum of water is the prerequisite for the application of terahertz technology to biomedicine. The choice of terahertz frequency is essential for achieving the biological effects of terahertz with high efficiency and low energy consumption. The complex hydrogen bond network of water possesses a broad terahertz absorption peak. Therefore, it is necessary to study the relation between the dynamics of the hydrogen bond network of water and its terahertz absorption spectrum. However, the research in this field is still lacking. Using molecular dynamics simulation methods, the terahertz absorption spectra of different water models at room temperature and pressure are studied in this work. Furthermore, taking the temperature as a variable, the dependence of the terahertz absorption spectrum of water on the strength of the hydrogen bond network is explored. It is found that rising temperature makes the terahertz absorption spectrum of the hydrogen bond network red-shift, indicating that the center frequency of the spectrum is strongly correlated with the strength of the hydrogen bond. Further studies show that there is a linear relationship between the hydrogen bond lifetime of water and the center frequency of vibration absorption peak of the hydrogen bond network. The underlying mechanism can be disclosed by imitating the hydrogen bonds in the hydrogen bond network as springs then using the spring oscillator model. These findings are conducive to understanding in depth the complex hydrogen bond network dynamics in water and promoting the study of terahertz biological effects.
2021, 70 (24): 248706.
doi: 10.7498/aps.70.20211807
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2021, 70 (24): 248701.
doi: 10.7498/aps.70.20211725
Abstract +
Potassium channels play an important role in repolarizing the nerve cell action potentials. There are many types of potassium channel proteins, and potassium channels allow potassium ions to specifically pass through the cell membrane, thereby maintaining the resting potential of nerve cells. In this paper, molecular dynamics simulation method is used to simulate the effects of 53.7 THz terahertz wave with different amplitudes on the secondary structure of KcsA potassium channel protein and the potassium ions rate. It is found in this study that under the action of the 53.7 THz terahertz wave, the number of alpha helices in KcsA potassium channel protein decreases, and the number of beta sheets and the number of coils increase. In addition, the 53.7 THz terahertz wave can accelerate potassium ions through the KcsA potassium channel. In this article, the effects of terahertz waves on potassium channel proteins are analyzed through the secondary structure of proteins, and a new perspective for the interaction between terahertz waves and biological functional molecules is presented as well.
2021, 70 (24): 240301.
doi: 10.7498/aps.70.20211677
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The size of nerve cell is comparable to the wavelength of terahertz (THz) wave. In this work, a new concept of weak resonance effect of nerve cells is proposed. The permittivity of intracellular fluid is measured experimentally by using a THz-TDS system, and the relationship between the permittivity of nerve cells and the frequency is obtained by fitting the double Debye model. The propagation characteristics of THz waves in nerve cells are studied by finite difference time domain. The results show that when the dielectric constant of nerve cell is higher than that of the external medium, THz wave can be enhanced in the nerve cell. Meanwhile, as the dielectric constant of the external medium increases, the resonance will be close to the cell membrane. And it shows the focusing property of THz waves, as a convex lens does. The weak resonance effect is related to the dielectric constant of the background medium, and increases with the cell size and frequency increasing. These results provide a new model to explain the interaction between THz wave and nerve cells, contributing to the study of the transmission mechanism of THz wave in biological nervous system.
2021, 70 (24): 248705.
doi: 10.7498/aps.70.20211779
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Methane hydrate (so-called flammable ice) has many advantages such as wide distribution, large resource reserves, high energy density, being clean and pollution-free, etc. Thus, it has attracted much attention since it was discovered. Unfortunately, its exploration encounters many difficulties, which involve mainly with the dissolution process of caged methane hydrate. Therefore, in this work the specific effect of THz electromagnetic wave on decomposition of the hydrate is explored through molecular dynamics simulations. Analyzing the vibrational spectrum of the hydrogen-bond network in methane hydrate, no specific absorption peak is found in the bulk water. Applying a THz wave at this specific frequency to the methane hydrate, the original hydrogen-bond network is broken, the coordinate number of water molecules for the methane decreases, and ultimately the methane frees from the water cage. The F4 ordered parameters further validate the phase change from the crystal water to liquid water under the same THz field irritation. It is also proved that this peak absorption frequency has a remarkable superiority over other frequencies in decomposing the methane hydrate, hence it has specificity. Our findings support the feasibility of non-thermally dissolving methane hydrate, which promises to promote the exploitation efficiency and development of new energy sources in the future.
2021, 70 (24): 244303.
doi: 10.7498/aps.70.20211729
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The future sixth-generation (6G) wireless network has advantages of global coverage, high spectrum efficiency, low cost, high safety, and higher intelligent level. The 6G technology can create ubiquitous intelligent mobile networks for human society. Terahertz wireless communication has the characteristics of high data transmission rate, low delay, and anti-interference, which may be widely used in 6G technology. This paper mainly introduces the planning vision, development status, and key 6G technology, and analyzes the terahertz devices, channels, communication systems, and the possible development trend of 6G technology.
2021, 70 (24): 240701.
doi: 10.7498/aps.70.20211996
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2021, 70 (24): 243101.
doi: 10.7498/aps.70.20211482
Abstract +
The physical properties and dynamics of molecules can be studied by the interaction between electromagnetic field and molecular system. The continuous development of terahertz technology provides a terahertz source capable of generating a sub-picosecond directional intense electric field. The generated intense-field terahertz wave has the same electric field intensity as the molecular local electric field environment, and on a sub-picosecond time scale of the directional electric field there can happen many ultrafast physical and chemical reactions. At present, the interaction between terahertz waves and molecules is limited mainly to the resonance interaction, that is, the molecules transition at different vibrational levels, caused through dipole interaction. In this work, based on the density functional theory calculation and the finite difference time domain solution method of Schrödinger equation, the intense non-resonance effect of intense terahertz wave electric field on hydrogen molecules is studied. The results show that under the action of intense terahertz wave sub-picosecond directional intense electric field, hydrogen molecule will produce an induced dipole moment. This dipole interacts with the external terahertz field, resulting in the fluctuation of proton probability density distribution and the change of vibration energy level population. Based on the non-resonant interaction between non-polar diatomic molecule hydrogen and intense terahertz wave, a unique way of producing the interaction between electromagnetic waves and molecules is displayed in this work, which is a method of studying the dynamics of non-polar molecules and molecules with weak polarity in intense terahertz field.
2021, 70 (24): 247802.
doi: 10.7498/aps.70.20211752
Abstract +
The electromagnetic wave in the terahertz region shows many promising properties, such as non-ionizing, sensitivity to weak resonance, and gradually becomes a basic and applied research hotspot of physics, information, materials, biology, chemistry and other disciplines. However, the analyte molecules tend to be of subwavelength size, and cannot have sufficient interaction with the incident terahertz wave. Small disturbances and subtle features are difficult to detect, which undoubtedly hinders the further development of the terahertz biochemical sensing and detection. The rapid development of terahertz metamaterials provides an alternative method to overcome this obstacle. The intense electromagnetic field enhancement induced by metamaterials allows the sensing and detection application to surpass the limitation of classical terahertz spectroscopy, which is due to the enhancement of the interaction between the analyte and terahertz. In recent years, a series of researches based on terahertz metamaterials combined with new materials, new structures and new mechanisms has offered new opportunities for the application of highly sensitive terahertz biochemical sensing and detection. In this paper, the recent advances in the application of terahertz metamaterials biochemical sensing are reviewed. The related concepts are briefly introduced and the influences of different factors on the sensing performance of metamaterial sensor are analyzed. According to the material selection and design strategies, the related researches of terahertz metamaterial biochemical sensing and detection are summarized. Furthermore, the novel strategy of terahertz metamaterial sensing and detection application based on multidisciplinary are presented, and the future development directions are also discussed, which will greatly conduce to expanding the practicality of terahertz sensing and detection.
2021, 70 (24): 248707.
doi: 10.7498/aps.70.20212030
Abstract +
Irradiation of terahertz electromagnetic wave including its short-wave band in infrared wave shows broad and important application prospects in biological science due to its noninvasive and nonionizing nature. Cell membrane is an important biological barrier for keeping cell integrity and homeostasis, and it is also the cellular structure that electromagnetic fields act first on in the case of terahertz irradiation. The responses of cell membrane to the electromagnetic fields are the mechanisms for most of the biological effects of terahertz irradiation. First, in this paper are expatiated the application safety of terahertz irradiation and its new application prospects in life medicine, neural regulation and artificial intelligence. Then, systematically described are the researches and developments in the biological effects of cell membrane under terahertz electromagnetic irradiation from the following four aspects: the dielectric response characteristics of phospholipid membrane to terahertz electromagnetic irradiation, the transmembrane transport of ions through membrane ion channel proteins under the irradiation, the transmembrane transport of macromolecules and ions through phospholipid membrane under the irradiation, and the potential applications and role of biological effects of cell membrane under the irradiation. Meanwhile, introduced in this paper are the scientific discoveries that terahertz electromagnetic irradiation is able to activate voltage-gated calcium channels, voltage-gated potassium channels and active transport calcium channels in cell membrane and to create hydrophilic pores on the phospholipid membrane of cell membrane. Finally, the directions of future efforts to study the biological effects of cell membrane under terahertz irradiation are presented.
2022, 71 (17): 178702.
doi: 10.7498/aps.71.20212419
Abstract +
Terahertz wave is an electromagnetic wave, whose wavelength is located between microwave wavelength and infrared wavelength. Based on low ionization and fingerprint characteristics, it has great potential applications in biomedical field, especially in the intraoperative localization and qualitative diagnosis of tumors. Glioma is the most urgent tumor for positioning qualitative diagnosis. Owing to its invasiveness and heterogeneity, it is easy to relapse after resection and has a significant influence on the nerve function of adjacent brain regions. Therefore, rapid determination of tumor boundary and pathological characteristics is an important prerequisite for accurate diagnosis, treatment and clinical research of glioma. Here, we summarize the biophysical technology of glioma diagnosis, and expound the new technique of terahertz wave and its research results in diagnosis of glioma. Furthermore, based on the research progress of integrated diagnosis of glioma histopathology and molecular pathology, we propose a hypothesis that different molecular subtypes of tumor tissue may have a consistent 'differential terahertz wave protein composition' of terahertz tumor subtype recognition mechanism. Finally, combining the biological characteristics of brain tissue and the potential of glioma marker detection in body fluids, we discuss the clinical application model and prospects of terahertz technologies in glioma detection.
