BIOLOGICAL (Human Body- tissues, cells, organs, skin, fluids, DMA, RNA, etc) ) EFFECTS OF TERAHERTZ (THZ) RADIATION http://docs.wixstatic.com/ugd/a5089d_721ea3c553c94f40852820d6e355598c.pdf Biological Effects of Terahertz Radiation Abstract Terahertz (THz) imaging and sensing technologies are increasingly being used in a host of medical, military, and security applications. For example, THz systems are now being tested at international airports for security screening purposes, at major medical centers for cancer and burn diagnosis, and at border patrol checkpoints for identification of concealed explosives, drugs, and weapons. Recent advances in THz have regarding the with this . Biological effects studies are a valuable type of basic science research because they serve to enhance our fundamental understanding of the mechanisms that govern THz interactions with . Such studies are also important because they often times lay the foundation for the development of future applications. In addition, from a practical standpoint, THz is also for the safe use of THz . Given the importance and timeliness of THz bioeffects data, the purpose of this review is twofold. First, to provide readers with a common reference, which contains the necessary background concepts in biophysics and THz technology, that are required to both conduct and evaluate THz biological research. Second, to provide a critical review of the scientific literature. Keywords Terahertz . THz . Thermal effects . Microarray . Cellular effects . Gene expression . Invited review . Biological effects . Review article . Radiation CONTENTS 1.Introduction …………………………………….. 2. Background: composition and function of biological structures ……………………………. 3. Terahertz interactions with biological materials 3.1. Fundamental principles 3.2. Biological origin of tissue absorption properties 3.3. Thermal response of tissue. G. J. Wilmink (*) : J. E. Grundt 711th Human Performance Wing, Radio Frequency Radiation Branch, Air Force Research 4. Thermal effects in biological materials 4.1. Organisms and tissues 4.2. Mammalian cells 4.3. Cellular organelles 4.4. Biological macromolecules 4.5. Microthermal effects 5. Terahertz biological effects research 5.1. Sources 5.2. Detectors 5.3. Equipment used for controlled exposures and dosimetry 5.4. General challenges and considerations 6. Methodology and study-by-study analysis of the THz bioeffects literature 6.1. Organism level studies 6.1.1. Vertebrates 6.1.2. Insects 6.1.3. Plants 6.2. Excised tissues. applications 1 stimulated renewed interest biological effects associated frequency range biological systems biological effects research necessary accurate health hazard evaluation, development of empirically-based safety standards, systems Comment [i]: carbon nanotubes (CNTs) and graphene have emerged as extraordinary low-dimensional systems with a variety of outstanding electronic and photonic properties, 1 − 7 including those ideally suited for terahertz THz) devices 6.3. Mammalian cells 6.4. Cellular organelles: lipid membranes 6.5. Biological macromolecules 7. Summary and future prospects Introduction energy of THz is level type of because of below the from eVs). Thus, are. This fundamental distinction is important vastly free to other free in that are is that only to cause direct. These direct effects are they result in the can cause In contrast,.terahertz portion electromagnetic does not but it can cause. For many years, data has been scarce at THz frequencies because suitable sources were not widely available. However, a recent surge in research activity has resulted in the development of many new types of sources and components. These new THz technologies have bridged the proverbial “THz Gap,” and are increasingly being integrated into a host of practical medical, military, and security applications. For instance, THz imaging and Electromagnetic Spectrum Frequency (Hz) Spectral bands 10 5 10 6 10 7 10 8 10 10 9 10 10 11 10 12 10 13 10 14 10 15 10 16 10 17 10 18 10 19 10 20 10 21 Radio waves -wave THz IR VIS UV X- rays – rays Frequency (THz): Wavelength ( m): Wavenumber (cm-1): Period (picoseconds): Photon energy (meV): Temperature (K): h c/ k = 1/ 0.1 3000 3.3 10.0 0.4 1.0 300 33.4 1.0 4.1 47.8 10.0 30 334.0 0.1 41.0 478.0 from from bulk frequency spectrum region occupies located. The THz region is between 21 The (THz) a large of the (EM) that is the (IR) and (MW) typically defined to include the frequencies ranging from 0.1 to 10 THz, where 1 THz equals 1012 Hz. In terms of other frequently used units, this range corresponds to the following: wavelength 1 (303000 m); wavenumber k (3.3334 cm-1); period t (0.110 picoseconds), temperature T (4.8478 K), and photon energy E (0.441 milli-electron volts) (Fig. 1). It is important to note that the infrared photons several orders magnitude energy required to ionize,or remove,valence electrons biological molecules typically, several “T-rays” classified non-ionizing radiation nonionizing and ionizing radiation generate different effects in biological structures. Perhaps,the most noteworthy difference ionizing radiation particles carry o water and to enough energy ionization effects t biomolecules.particularly harmful biological structures formation of highly reactive radicals nonionizing secondary or indirect damage biomolecules radiation generate radicals biological structures, thermal effects indistinguishable effects observed heating because microwave regions as a which T = h /kB 4.8 Fig. 1 The Terahertz (THz) band of the electromagnetic spectrum. sensing techniques are presently used at major airports for security screening purposes [1, 2], at major medical centers for cancer and burn diagnosis , and at border patrol checkpoints for identification of concealed explosives, drugs, and weapons . Widespread deployment of new THz applications has prompted increased scientific interest regarding the biological effects associated with this frequency range. In recent years, many timely investigations have been performed to investigate the possible biological effects associated with THz radiation . Unfortunately, however, a comprehensive review has not yet appeared in the literature which both discusses the fundamental interaction mechanisms, and also critically reviews the bioeffects studies that have been conducted to date. Thus, the purpose of this review is twofold. First, to provide readers with a common reference, which contains the necessary background concepts in biophysics and THz technology that are required to both conduct and evaluate THz biological research. Second, to provide a review and analysis of the studies reported in the literature on the topic of THz bioeffects. This review is divided into seven sections. The first section provides a general introduction to the THz spectral band. The the of and an of the irradiation of materials. The fourth section summarizes the primary thermal effects that are observed in biological materials at an organism, tissue, cellular, organelle, and molecular level. The concepts described in this section are valuable because they provide the foundation to understand THz-induced effects at all levels of biological organization. In addition, they give the reader the tools to determine whether the effects observed in THz reports can be fully attributable to the temperature rise generated during exposure. The fifth section surveys the major types of THz sources, detectors, and equipment that are used in biological research. This section also addresses the common challenges and considerations that investigators face in this field. Following the description of THz technologies, the sixth section then describes our methodology to survey the literature. This section provides a comprehensive review and “study-by-study” analysis of the THz bioeffects reports that appear in the literature. The review concludes with a summary section that addresses challenges and future opportunities in this field. 2 Background: composition and function of biological structures THz-induced biological effects are influenced by two general factors: the THz exposure (i.e., etc.) and the of the . This section provides background on the chemical composition and function of skin, the. It also discusses energy deposition processes and temperature transients that result from THz of THz with and 3 second section describes composition function biological structures: skin tissue, mammalian cells,organelles, biological macromolecules. The third section provides fundamental mechanisms governing interaction radiation biological materials overview the parameters frequency, power,exposure duration, composition and/or properties biological target largest and primary biological target for THz radiation. Please note, the is also an an to properties. 2.1 and Skin of two (Fig. 2a). The skin and cell for THz in this we have not . This section also serves to provide the necessary foundation that is required to understand the biological origin of tissue optical important for this cells are type of skin cell. The of a toasaquamousepithelial a biological target effort details make section more concise tissue . The main function of the epidermis is is by 95% of all to and to provide a physical barrier that not only protects against water loss, but also prevents harmful external agents from entering. This protective barrier epithelial tissue consists of five distinct layers or strata: (sc), (sl), (sg), (ss), and (sb) (Fig. 2a). as they the to the include: increases in keratin production, decreases in water content, decreases in cellular metabolism, loss of nuclei and organelles, and cellular flattening. a b Plasma membrane Nucleus Cytosol Inorganic ions RNA H2O Ribosome DNA Cytoskeleton Mitochondria Endoplasmic reticulum O2 ATP Golgi apparatus Lysosome H+. In brief, these changes cornea 4 radiation; however,provided Human skin: structure chemical composition consists primary layers: an outer epidermis and an underlying dermis epidermis consists of water, keratin proteins, melanin granules,several types, including langerhans, melanocytes, keratinocytes keratinization achieved keratinocytes.in the Roughly keratinocytes,thus,they are the most common Keratinocytes are genetically programmed undergo cellular differentiation process known as keratinization. process results formation layered barrier referred stratified squamous tissue. S stratum corneum lucidum Keratinocytes granulosum spinosum basale undergo several phenotypic changes progress from inner outer stratum Protein Extracellular matrix Fig. 2 (ab). a. Skin anatomy. Histological cross section of porcine skin tissue (Hematoxylin and Eosin stain at 40X magnification). Epidermis (epi), basement membrane (bm), dermis (d). Legend for magnification: stratum corneum (sc), stratum lucidum (sl), stratum granulosum (sg), stratum spinosum (ss), and stratum basale (sb) b. Cellular chemistry and morphology. Image created with Ingenuity IPA software. Although keratinocytes in the sb layer are devoid of keratin, they do have high concentrations of melanin, a pigment responsible for skin (i.e., Fitzpatrick skin type). Melanin granules are produced by melanocytes, and they are transferred to keratinocytes via cytocrine secretion mechanisms. To date, studies have not been performed to characterize the optical properties of melanin at THz frequencies; however, comparable studies have been conducted at optical frequencies. These studies report that the absorption coefficient (a) of melanin decreases with wavelength, and can be approximated as: a (cm-1) = 1.70×1012 ×1-3.48 (nanometers, nm) . Assuming this trend continues into the THz region, melanin absorption is probably weak at THz frequencies (i.e., a 10-4 cm-1). In addition to contributing to skin color, the sb layer also The BM is the and in of the the to few of pattern color. It and have cassists primarily formation basement membrane (BM).layer that of type IV .Iseparates epidermis dermis. consists collagen, laminin,entactin, sulfated proteoglycans nterestingly, date,studies characterized the optical properties these biomolecules frequencies . Such information would likely improve the accuracy of computational models that are currently used to predict THz-tissue interactions. Immediately below the epidermis lies the dermis. The dermis provides skin with shape and structural integrity, and it ranges in thickness across the human body between 0.3 and 4 millimeters (Fig. 2a). The dermis consists of dermal fibroblasts that are anchored in an extracellular matrix (ECM). The ECM consists of fibrillar collagen embedded in a ground substance material. It is interesting to note that healthy fibrillar collagen exhibits a characteristic with a of ~60 nm, this The significance of this feature will be described in greater detail in Section 4.1. is of and that their own . Due to this property, large volumes of water typically reside in the at THz banding thermally damaged c gylcosaminoglycans ground substance of the dermis. This is the THz. at THz is to note , thus, (see collagen loses Ground substance primarily comprised Sections 3.1-3.3). 2.2 Structure and chemical composition of mammalian cells Cells in the human body come in a wide variety of sizes and shapes; however, virtually all cells (Fig. 2b). First, all cells are enclosed by an outer protective barrier known as the plasma membrane. The plasma membrane provides a selective barrier between intracellular contents and extracellular fluids. The is composed of a periodicity water,collagen,are whereas signature banding pattern. elastin,proteoglycans,(GAGs). GAGs hydrophilic molecules volume sequester water volumes roughly 1000 times property important because water primary chromophore frequencies presence strongly governs where energy deposited share certain characteristics plasma membrane phospholipid bilayer,which contains integral proteins Comment [i]: Carbon C 60 would then bind with these carbons and make a person even more sensitive to a terra hertz hit Comment [i]:are are Comment [i]:that for and small digesting Lysosomes compartments responsible damaged macromolecules,which are collected during phagocytosis autophagy, endocytosis,processes Mitochondria are a of that are all second the cell,’ the of in the of is to of class cytoplasmic organelles present in nearly cells. Nicknamed powerhouse mitochondria main function generate chemical energy adenosine form triphosphate (ATP).and . The phospholipid bilayer is comprised of two elements: polar are the outer exact of on the cell type, and ratio of cholesterol composition,membranes hydrophilic surface,and in the tails are in the interior of. The degree of saturation of the carbon-carbon hydrocarbon which bonds in the hydrocarbon tails governs the structure and order of the bilayer, where saturated hydrocarbons chains are more restricted and unsaturated chains are more fluid . Overall, the properties and present bilayer interior heads, which oriented towards thermal sensitivity plasma depend membrane saturated versus 27]. Two distinct regions exist inside the plasma membrane of all cells: and cytoplasm (Fig. 2b). The cytosol makes upthe largest volume of cells, and it is primarily composed of and ions (i.e.,unsaturated hydrocarbons roles in a thick and ), and cytoskeleton filaments.to cells, and they also play key. The is . that that are cytosol water,organic inorganic sodium,potassium, magnesium,calcium,phosphate, chloride Cytoskeleton filaments provide structural support intracellular transport and (pH ~7.17.2) liquid that cellular division cytoplasm alkaline contains all organelles. Organelles are vital in specialized membrane-bound compartments provide cellular functions.