TECHNICAL TESTING AND CONFIRMATION OF THE PHOTOCHEMICAL PROPERTIES OF A NEW NANOSECOND SEMICONDUCTOR LASER GENERATOR FOR MEDICAL USE

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1 International Journal of Mechanical Engineering and Technology (IJMET) Volume 9, Issue 11, November 2018, pp , Article ID: IJMET_09_ Available online at aeme.com/ijmet/issues.asp?jtype=ijmet&vtype= =9&IType=11 ISSN Print: and ISSN Online: IAEME Publication Scopus Indexed TECHNICAL TESTING AND CONFIRMATION OF THE PHOTOCHEMICAL PROPERTIES OF A NEW NANOSECOND SEMICONDUCTOR LASER GENERATOR FOR MEDICAL USE A. A. Chunikhin, E. A. Bazikyan, N. A. Chunikhin Moscow State University of Medicine and Dentistry, A.I. Evdokimov Departmentt of oral surgery, Moscow, Russian Federation K. M. Akimova, A. A. Kalantaryan, A. T. Manukyann I.M. Sechenov First Moscow State Medical University Department of prosthetic dentistry, Moscow, Russian Federation ABSTRACT Laser technologies in medicine and dentistry are promising. The directional action of the laser beam allows performing minimally invasive surgical interventions. The photochemical effect of singlet oxygen on the pathological tissues generated from molecular oxygen by the action of laser light defines a whole direction in the development of laser technology for medical use. This study presents a new laser device based on semiconductor crystals with the possibility of operating in a nanosecond pulsed radiation mode. The purpose of the study was to test the technical parameters of the device and to conduct photochemical laboratory experiments to determine the possibility of generating singlet oxygen in biochemical environments. Technical testing of a new laser device included a test to maintain a given average power, spectral parameters of laser radiation and modulation of nanosecond radiation pulses for a long period of operation of the device (for 1 hour). In addition, photochemical experiments were carried out to determine the efficiency of generation of singlet oxygen in model biochemical environments in pulse mode of radiation, in comparison with continuous mode. The results of technical testing of the device confirmed the stability of the technical characteristics of the device, even after long- laser term operations. Laboratory photochemical testing of a new nanosecond generator proves that pigment-free laser generation of singlet oxygen using a pulsed low-frequency emission mode is more efficient than continuous radiation. The collected data allow us to recommend this device for further preclinical and clinical trials, which ultimately can be a start of a new direction in the development of medical laser technologies editor@iaeme.com

2 Technical Testing and Confirmation of The Photochemical Properties of A New Nanosecond Semiconductor Laser Generator For Medical Use Keyword: Photodynamic Effect, Singlet Oxygen, Laser Radiation, Nanosecond Pulsed Laser, Semiconductor Laser. Cite this Article: A. A. Chunikhin, E. A. Bazikyan, N. A. Chunikhin, A.I. Evdokimov, K. M. Akimova, A. A. Kalantaryan and A. T. Manukyan, Technical Testing and Confirmation of The Photochemical Properties of A New Nanosecond Semiconductor Laser Generator For Medical Use, International Journal of Mechanical Engineering and Technology, 9(11), 2018, pp INTRODUCTION In modern medicine, the use of laser technology is quite widespread, since they are described as a humanistic therapy. Laser generators make it possible to obtain monochromatic radiation of high power and due to this, selectively hit the necessary targets avoiding the damage to other structures. Treatment using laser technology is characterized by low invasiveness, low systemic toxicity, and lack of genotoxicity [1]. Low-intensity laser radiation has fibrin and thrombolytic properties, has anti-inflammatory and anti-edema effects [2]. Photochemical effects of laser radiation underlie the method of treatment using photodynamic (PDT) laser therapy. The result consists of the combined action of three components - a photosensitizer, laser radiation and the formation of oxygen into molecular singlet oxygen. Due to the high oxidative activity, singlet oxygen enters into chemical reactions with biological structures, triggering the reaction of lipid peroxidation in the cell or in the extracellular space. The destruction of biological substrates also leads to the formation of free radicals, which have a secondary damaging effect on cells. New medical technologies using photodynamic therapy have been developed in various branches of medicine: ophthalmology, otorhinolaryngology, urogynecology, operative dermatology, cosmetology, surgery, dentistry and maxillofacial surgery [3]. In addition, laser technology allows performing surgical interventions with minimal invasion, which is especially important in performing reconstructive operations in the maxillofacial area [5; 7; 12]. At this stage of development of photodynamic therapy, photochemical reactions in tissues are impossible without photosensitizers. A large number of compounds can be used as photosensitizers: hematoporphyrin, δ-aminolevulinic acid, phthalocyanine, benzoporphyrins, bacteriochlorophyll, chlorin e6 derivatives [4; 9]. The degree of penetration of the photosensitizer in the tissue depends on its concentration. However, with increasing concentration of the drug increases its toxicity. The selectivity of the photosensitizer depends on the main substance from which the preparation is made. In addition, experiments have shown that tissue destruction does not occur with the same selectivity with which sensitizers accumulate. It is of interest to search for the possibility of photodynamic therapy in tissues without the use of photosensitizers, i.e. the method of direct generation of singlet oxygen according to the following schema: 1. 3 O 2 + hv 1 O 2, 2. 1 O 2 + Substrate Oxidation, It is known that the maximum tissue permeability stays in the spectrum of far red and near-ir region of nm. In addition, experiments have shown that the maximum absorption of oxygen occurs upon radiation with a wavelength close to 1270 nm, and editor@iaeme.com

3 A. A. Chunikhin, E. A. Bazikyan, N. A. Chunikhin, A.I. Evdokimov, K. M. Akimova, A. A. Kalantaryan and A. T. Manukyan nanosecond pulsed laser radiation allows to penetrate deeper into the tissues without their substantial heating [1; 6; 8]. Currently, in the conditions of the need to improve competitiveness in the world market, there is an increasing task to develop innovative Russian enterprises and to create new innovative products, including such products as medical lasers [10]. Today such laser generators are being developed and there are prototypes which need tests of physical parameters and photochemical properties to be held [11]. The aim of the work was the study of the physical parameters of a nanosecond diode laser and a comparative evaluation of photochemical effects in vitro. 2. MATERIALS AND METHODS We used a laser device for medical use with a touch control display on the basis of semiconductor crystals, designed by LLC New Surgical Technologies (Moscow, Russia) on the instructions of the research group in accordance with the technical documentation developed at MSUMD named after A.I. Evdokimov at the Department of Oral Surgery. The device has a main infrared (IR) emitter with a wavelength corresponding to the maximum absorption of oxygen ( nm). The emitter operates in a continuous mode with a variable radiation power in the range of up to 1.0 W and four pulse modes with the generation of nanosecond pulses with a fixed radiation power. The radiation is focused in a 400 μm optical light guide. The infrared emitter is a strip diode laser based on a quantum confinement double heterostructure with an extended waveguide. The laser heterostructure was fabricated by the MOS-hydride gas-phase epitaxy in the AlInGaAs / InP solid solutions system. The structure consists of InP emitters, AlInGaAs waveguide with a total thickness of 1.04 μm, two AlInGaAs quantum wells with a thickness of 75Å each and AlInAs energy barrier from the p- emitter with a thickness of 100 nm (Figure 1). Figure 1 Schematic zoned energy diagram of the laser structure used in the under study device. The laser power was determined using an Ophir ORION-TH power meter with an Ophir 20C-SH measuring head. Using the Aktakom ADS-2121M oscilloscope, the variability of laser radiation in one of the operating modes was checked. To study the emission spectrum in all laser modes, we used a computerized setup based on a MDR-206 monochromator and a photodiode device with a germanium photodiode, calibrated with a wavelength using a LGN-207B helium-neon laser. In order to track possible changes during a long work session, for each mode a series of spectra was obtained from 50 radiation sessions, which were recorded every 10 min after the laser was switched on editor@iaeme.com

4 Technical Testing and Confirmation of The Photochemical Properties of A New Nanosecond Semiconductor Laser Generator For Medical Use To record singlet oxygen, we used model media aqueous detergent solutions (singlet oxygen trap) of 1,3diphenylisobenzofuran (DPIBF). DPIBF forms a colorless endoperoxide when it interacts with singlet oxygen. The monitoring of the singlet oxygen release reaction was carried out using a fading spectrophotometer with laser irradiation of the main absorption band of traps at 414 nm wavelength. For the accuracy of determining the responsibility of singlet oxygen for the loss of the substrate, quenchers of singlet oxygen were added to the solution. In order to free the solutions from dissolved oxygen, the solutions were sparged with nitrogen. Square quartz cuvettes with an optical path length of 1 cm were used. The volume of samples in cuvettes was always up to 1.5 ml. The light guide was placed close to the cuvette with the trap solution. The duration of the sample irradiation session was chosen so that the fading effect of SDS was reliably measurable, but not too strong. The exposure time was 60 minutes with an average power of 1 W. The optical density of the solutions (at 414 nm) was measured before and after emitting. To record the fading of the singlet oxygen trap, a Shimadzu UV-1601PC spectrophotometer was used. The trap fading rate was calculated from the result of the optical density of the solution. The study was carried out on different operating modes of the laser in order to identify the optimal parameters of laser emitting for generating singlet oxygen. In each mode of radiation, a series of studies including 50 sessions was carried out. The results were processed statistically with the calculation of the arithmetic mean and the error of the arithmetic mean. 3. RESULTS Technical measurements of power made it possible to establish that the range of power control is possible in the range from 0.05 to 1.0 W in increments of 0.01W in the continuous emission mode. Pulse radiation modes have preset power levels of 0.25; 0.5; 0.75 and 1 W. The power level in all modes is stable, it stays exactly at the level stated in the technical documentation. Smooth adjustment of the power level in continuous mode in 0.01 W increments has high accuracy and corresponds to the stated readings. As a result of research, it was found that, both in stationary mode of operation and in pulsed modes, the emission spectrum during continuous operation of the device for more than 1 h does not shift and stays within 1270 ± 2 nm. It is important to note that the laser emission spectrum did not depend on the set power level. (Figure 2). Figure 2 Laser emission spectrum in pulsed mode 0,75W The oscillogram obtained by measuring the pulse modes of radiation of the device shows that the signal has a significant modulation, which confirms the impulsiveness of the radiation. In this case, in all modes of different power, the pulse duration stayed 100 ns, and the time interval between pulses was about 200 ns, which corresponded to a frequency of 500 khz (Figure 3) editor@iaeme.com

5 A. A. Chunikhin, E. A. Bazikyan, N. A. Chunikhin, A.I. Evdokimov, K. M. Akimova, A. A. Kalantaryan and A. T. Manukyan Figure 3 Oscillogram of a laser signal in a pulse mode Photochemical experiments were performed with a radiation power of 0.75W. In photochemical experiments, 1,3-diphenylisobenzofuran was used as a singlet oxygen trap. To estimate the efficiency of generation of singlet oxygen by laser radiation, a model system was used, which was an air-saturated solution of 1,3-diphenylisobenzofuran (DPIBF) in acetone. It is characterized by a rather long lifetime of singlet oxygen (51 μs), and therefore the effect of decreasing optical density of DPIBF reacting with singlet oxygen is easily measurable. The quickness of fading of a chemical trap, both in continuous operation mode of the device and in pulse modes, directly depends on the time of exposure. (Figure 4). Figure 4.The change in optical density of a chemical trap in an acetone solution depending on the irradiation time under the action of a laser in a pulse mode with power 0,75W The graph in Figure 4 shows the quickness of change of the optical density of a chemical trap under the action of a pulse mode with a radiation power of 0.75 W depending on the exposure time. Before emitting, the optical density is at a level of 0.9 rel. units. When the solution is emitted for 6 min, the optical density drops to 0.8, while continuing to radiate to 12 min, the density drops to 0.65 rel. units. When the solution is emitted for 18 min, the density drops to In our study, we performed irradiation for 1 hour. Table 1 shows the relative rates of fading of the trap in an acetone solution under the action of the device. The figures in the table correspond to the decreasing speed of the optical editor@iaeme.com

6 Technical Testing and Confirmation of The Photochemical Properties of A New Nanosecond Semiconductor Laser Generator For Medical Use density of the trap, normalized to 1 W per minute of laser emitting. Each digit is the average of 50 independent measurements (statistical error ± 5%). Table 1 Efficiency of photodestruction of a singlet oxygen trap with laser excitation of dissolved oxygen molecules in acetone solution The fading rate DPIBF (Rel. Unit.) Normalized to the power of the substance laser radiation (W) with different operating modes of the laser continuous 0,75W pulse 0,5W pulse 0,75W Acetone 0,065 0,049 0,043 The results of the experiments clearly demonstrate that in the pulse modes the rate of fading of the chemical trap is higher than during irradiation in the continuous mode of the laser. The difference in the fading rate of the trap between the nanosecond pulsed mode with a radiation power of 0.75 W and a continuous radiation mode is 22 points, measured in relative units of the optical density of the solution. It should be noted that the decrease in optical density after irradiation of the solution during the first 20 minutes is the most active, as it can be seen while comparing the data of Figure 4 and Table 1. In the first 18 minutes of irradiation, the trap density decreases by 35 points of relative units, while in the next 42 minutes of exposure a decrease in density occurs by 12 points. 4. DISCUSSION The experiments carried out showed that the laser device for medical use constructed on the basis of the documentation, fully complies with the set medical and technical tasks and requirements. The laser power at the set parameters does not change during long-term operation of the device. The power settings correspond exactly to the specifications set on the control panel of the device. Experiments to determine the emission spectrum and wavelength stability during long-term operation of the device showed that the laser radiation spectrum of the device stays within 1270 ± 2 nm. Spectral measurements performed as a result of 50 switching-ons of laser radiation for 1 h showed that within an hour in a pulsed mode, the shift occurs at 2 nm, which represents 0.15% of the declared wavelength and does not affect on the accuracy of photochemical experiments carried out. The accuracy of the pulsed radiation mode is important for the further medical use of the device. Technical testing using an oscilloscope showed that the device corresponds to the required parameters, while operating in pulse mode. It operates stably with a pulse duration of 100 ns, with the interval between pulses of 200 ns and a radiation frequency of 500 khz. Photochemical experiments to determine the potential of laser radiation with these characteristics for the generation of singlet oxygen from molecular oxygen in biochemical models have shown a high efficiency of radiation with a given wavelength for the generation of singlet oxygen. An experimental study was carried out with an acetone solution with 1,3- diphenylisobenzofuran, which is a chemical trap of singlet oxygen. The rate of fading of the trap was used to determine the efficiency of laser radiation from the generation of singlet oxygen. Experiments have shown that the efficiency of generation of singlet oxygen is higher by more than 30% compared with the use of continuous radiation using nanosecond pulsed radiation with a frequency of 500 khz editor@iaeme.com

7 A. A. Chunikhin, E. A. Bazikyan, N. A. Chunikhin, A.I. Evdokimov, K. M. Akimova, A. A. Kalantaryan and A. T. Manukyan 5. CONCLUSION The collected data obtained during the study shows that the tested laser device has stable technical characteristics even after prolonged operation. The results obtained in the analysis of photochemical laboratory tests of the device, suggest that the destruction of biological tissues rich in oxygen is possible under the action of laser radiation with a wavelength of 1270 nm. The ultra-short pulse laser radiation modes developed and embodied in this device with the ability to generate nanosecond pulses, contribute to the efficient generation of singlet oxygen in biochemical models by more than 30% compared to the continuous radiation mode. The data obtained during the photochemical experiments is fully correlated with the understanding of the short lifetime of singlet oxygen and the powerful ultrashort emission of laser energy contributing to the total pumping of singlet oxygen and its population in solutions. The designed laser device operating in a nanosecond pulse radiation mode allows to generate powerful short pulses of laser radiation, which increases the peak power of the light flux without substantial heating of the tissues. The stated characteristics, confirmed by technical testing, as well as the results of photochemical experiments, open up broad opportunities for the development of new areas of laser technology for medical use. It is important to create a laser device on semiconductor crystals, since it provides the ability to design compact devices with unique radiation parameters. The positive results obtained in this study are the first step in the cascade of experiments and allow you to proceed to the preclinical and clinical trials of the new laser device, and also open up opportunities for the development of a new laser microsurgery technology with the effects of singlet photo oxidative therapy. REFERENCES [1] Voronova, O.S, Gening, T.P., Svetukhin, V.V. (2012). Effect of femtosecond laser radiation on indicators of oxidative stress in tumor tissue in experimental cervical cancer.fundamental'nyeissledovanija, 1, [2] Boyko, V.I., Laricheva, L.P., Degtyareva, L.M. (2008). The mechanism of action of laser radiation on biological objects.elektronika i svjaz '.Tematicheskijvypusk Problemyjelektroniki, 2, [3] Gening, T. P., Voronova, O. S., Dolgova, D. R., Abakumova, T. V., Zolotovsky, I. O., Sholokhov, E. M., Kurkov, A. S., Gening, S. O. (2012). Analysis of the effectiveness of the use of continuous laser radiation with a wavelength of 1265 nm for the initiation of oxidative stress in the tissue of a solid malignant tumor.quantum Electronics, 42 (9), [4] Geinits, A.V., Sorokaty, A.E., Yagudaev, D.M., Trukhmanov R.S. (2006). Modern view on the mechanism of photodynamic therapy.photosensitizers and their bioavailability.urology, 5, [5] Robustova, T.G., Bazikyan, E.A., Ushakov, A.I., Dayan, A.V., Serova, N.S., Ushakov, A.A. (2008). A comprehensive clinical and radiological approach for reconstructive surgeries and sinus lifting in the upper jaw for dental implantation.rossijskajastomatologija, 1 (1), [6] Chunikhin, A. A., Bazikyan, E. A., Zayratiants, O. V. (2017). Evaluation of the effectiveness of nanosecond laser therapy of periodontal disease in the experiment.rossijskajastomatologija, 10(4), 3-7. doi.org/ /rosstomat [7] Bazikyan, E. A., Chunikhin, A. A. (2016). Minimally invasive laser technologies based on robotic multifunctional complexes in maxillofacial surgery and dentistry. Rossijskijstomatologicheskijzhurnal, 20(5), [8] Anquez, F., Courtade, E., Sivéry, A., Suret, P., &Randoux, S. (2010). A high-power tunable raman fiber ring laser for the investigation of singlet oxygen production from editor@iaeme.com

8 Technical Testing and Confirmation of The Photochemical Properties of A New Nanosecond Semiconductor Laser Generator For Medical Use direct laser excitation around 1270 nm. Optics Express, 18(22), doi: /oe [9] Anquez, F., El Yazidi-Belkoura, I., Randoux, S., Suret, P., &Courtade, E. (2012). Cancerous cell death from sensitizer free photoactivation of singlet oxygen.photochemistry and Photobiology, 88(1), doi: /j x [10] Akhmetshin, E. M., Vasilev, V. L., Mironov, D. S., Yumashev, A. V., Puryaev, A. S., & Lvov, V. V. (2018). Innovation process and control function in management. European Research Studies Journal, 21(1), [11] Chunikhin, A. A., Bazikyan, E. A., &Pikhtin, N. A. (2017). A laser unit for photodynamic therapy and robot-assisted microsurgery in dentistry.technicalphysicsletters, 43(6), doi: /s [12] Utyuzh, A. S., Yumashev, A. V., Lushkov, R. M. (2016). Clinical example of orthopedic treatment of a patient after mandible resection caused by sarcoma with the use of dental implants.clinical Dentistry, 4, editor@iaeme.com