JP2005074081A - Laser therapeutic apparatus and cytoclasis method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a therapeutic apparatus and a cytoclasis method for selectively destroying lesion cells. <P>SOLUTION: This laser therapeutic apparatus irradiate the lesion cells such as cancer cells with pulse laser beams to cause multiphoton absorption of lesion intracellular molecules. The intracellular molecules are ionized by multiphoton absorption to selectively destroy the lesion cells. A multiphoton absorption process is a process of molecules absorbing two or more photons simultaneously to excite an electron state. With the lesion cells irradiated with laser beams in predetermined conditions, the lesion intracellular molecules are ionized to produce semi-free electrons, and plasma is generated to destroy the cell membranes of the lesion cells. The lesion cells can thereby be treated selectively. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a laser treatment apparatus and a cell destruction method, and more particularly to a laser treatment apparatus and a cell destruction method that destroy cells by ionization caused by multiphoton absorption.

  In recent years, cancer is one of the most common causes of death in humans, and various treatment methods have been studied for many years. One cancer treatment is surgery. Surgical treatment removes the cancerous part by surgery. If all the cancer tissue can be removed, the cancer can be cured. However, surgical resection removes not only cancer tissue but also surrounding tissues at the same time. For this reason, there is a problem that it can lead to organ function deterioration and malfunction. Surgical therapy in which cancer tissue is excised using high frequency or laser light instead of a scalpel can reduce the amount of bleeding and reduce the influence on the human body as compared with conventional surgery. However, it is inevitable to simultaneously remove the tissue surrounding the cancer tissue.

  Another cancer treatment is radiation therapy. Radiotherapy kills and treats cancer cells by irradiating cancer tissue with radiation. Unlike surgical surgery, there are relatively few tissue defects. However, there is a problem that the irradiation of the body can cause a decrease in the body's immunity and the function of each organ. Alternatively, as another cancer treatment method, chemotherapy is known in which treatment is performed by administering an anticancer agent. Depending on the type of cancer, only chemotherapy is possible and is particularly useful in the treatment of these cancers. However, since anti-cancer drugs have strong side effects, there is a problem in that the function is lowered not only to cancer cells but also to normal cells, and sometimes destroyed.

  As described above, in cancer treatment, it is an important factor to surely destroy cancer tissues and to prevent side effects and adverse effects on the human body or healthy cells. In view of such a point, non-surgical therapy using a laser has been proposed. One of them is laser transpiration. Laser ablation is a laser ablation technique that irradiates a tumor with high-power laser light to evaporate the tumor. Although excellent in that the tumor is directly evaporated, there is a problem that when the treatment inside the tissue is performed, the surface of the tissue is affected by the high-power laser beam, and thermal damage around the tumor cannot be avoided.

  On the other hand, photodynamic therapy has been proposed as another laser therapy (see, for example, Patent Document 1). Photodynamic therapy is a combination of photosensitizers and site-specific irradiation that results in a therapeutic response in certain tissues such as tumors. When the drug absorbs photons, it becomes excited and becomes effective. The above-mentioned prior literature proposes a two-photon excitation method as a preferable method instead of the single-photon excitation method as a process for exciting a drug. Two-photon excitation is excitation between energy levels induced by simultaneously absorbing two photons. A photosensitizer present in cancer cells is excited to a high energy level by simultaneously absorbing two photon energies, and the photosensitizer exhibits a therapeutic effect.

  Compared with single photon excitation, two-photon excitation suppresses energy absorption outside the condensing region and can penetrate deep into the tissue. Also, spatial control of the processing unit is possible. Thus, the use of two-photon excitation in photodynamic therapy improves the penetration depth and spatial control issues, as well as improved therapeutic performance and activation sites for photodynamic therapeutic agents. Additional improvements are achieved by improving disease specificity in the selection of.

  However, the above-described conventional treatment method using two-photon excitation of a photosensitive agent needs to accumulate a photodynamic therapeutic agent in a tumor cell, and thus certain limitations arise in the treatment of focal tissue. For example, some photodynamic therapeutic agents can have side effects on the human body. Alternatively, some photodynamic therapeutic agents may exert a therapeutic effect only in limited conditions. For this reason, it is required to obtain a treatment method that can more effectively suppress side effects on healthy cells or the human body and selectively destroy the lesion tissue.

JP-T-2002-528472

  The present invention has been made in view of the above prior art, and one object of the present invention is to provide a therapeutic apparatus capable of effectively selectively destroying lesion cells, and a method of destroying lesion cells.

According to a first aspect of the present invention, there is provided a laser treatment apparatus for destroying a lesion cell, comprising: a laser light source that outputs a pulsed laser beam; an optical unit that guides the pulsed laser beam to a lesion cell; and the laser light source comprising: A control unit that controls, so that the lesion cell is destroyed by ionizing molecules due to multiphoton absorption in the lesion cell irradiated with the pulse laser beam. , Controlling the laser light source. By having this configuration, it is possible to selectively destroy lesion cells.
The treatment device destroys the lesion cells with one pulse of laser light. This can prevent unwanted thermal damage to surrounding cells.

  Alternatively, in the lesion cell, plasma is generated by ionization of a plurality of molecules, and the membrane forming the lesion cell is destroyed. Furthermore, plasma is generated by the cascade laser-induced irradiation of molecules in the lesion cells, which induces ionization in a cascade manner. This greatly increases the absorption of light energy, and can effectively destroy the lesion cells.

  It is preferable that the control unit controls the laser light source so that a peak energy of the pulsed laser light applied to the lesion cell is 10 KW or more. More preferably, the peak energy of the pulse laser beam is 20 KW or more. Thereby, ionization of intracellular molecules can be effectively induced.

  It is preferable that the control unit controls the laser light source so that a pulse width of the pulse laser light applied to the lesion cell is 10 ps or less. More preferably, the pulse width of the pulse laser beam is 1 ps or less. As a result, thermal damage to other cells can be suppressed and ionization of intracellular molecules can be effectively induced.

  Preferably, the optical means includes an optical fiber that transmits a pulse laser beam, and the control unit controls the pulse width of the pulse laser beam output from the laser light source to be not less than 1 ps and not more than 10 ps. . Thereby, even when an optical fiber is used, ionization of intracellular molecules can be effectively induced.

  It is preferable that the control unit controls the laser light source so that a wavelength of the pulsed laser light applied to the lesion cell is 700 nm or more and 900 nm or less. More preferably, the wavelength of the pulse laser beam is not less than 750 nm and not more than 850 nm. Thereby, ionization of intracellular molecules can be effectively induced.

  According to a second aspect of the present invention, there is provided a method for destroying a lesion cell by irradiating a pulsed laser beam, the step of irradiating the lesion cell with a pulsed laser beam, and the lesion. A step of ionizing a plurality of molecules in the cell due to multiphoton absorption, and a step of destroying the lesion cells by light absorption of the lesion cells having the plurality of ionized molecules. By having this configuration, it is possible to selectively destroy lesion cells.

  ADVANTAGE OF THE INVENTION According to this invention, the treatment apparatus which can treat a lesion part effectively can be provided.

  Hereinafter, embodiments to which the present invention can be applied will be described. The following description is to describe the embodiment of the present invention, and the present invention is not limited to the following embodiment. For clarity of explanation, the following description is omitted and simplified as appropriate. Further, those skilled in the art will be able to easily change, add, and convert each element of the following embodiments within the scope of the present invention.

  FIG. 1 is a block diagram showing a schematic configuration of a laser treatment apparatus 100 according to an embodiment of the present invention. The laser treatment apparatus 100 according to this embodiment irradiates a lesion cell such as a cancer cell with a pulsed laser beam, and causes multiphoton absorption of molecules in the lesion cell. Multiphoton absorption ionizes intracellular molecules and selectively destroys focal cells. The multiphoton absorption process is a process in which a molecule absorbs a plurality of two or more photons simultaneously, and an electronic state is excited. By irradiating a lesion cell with laser light under a predetermined condition, molecules in the lesion cell are ionized, and the lesion cell can be selectively destroyed and treated. The treatment apparatus of this embodiment can be applied to treatment of various lesion cells, but is particularly suitable for treatment of cancer cells.

  In FIG. 1, a laser treatment apparatus 100 includes a laser irradiation system that performs laser irradiation on lesion cells, an illumination system that illuminates the lesion, and an observation system that observes the lesion. The user can selectively treat the lesion cells with the laser irradiation system while observing the lesion portion illuminated by the illumination system with the observation system. The laser irradiation system includes a laser light source 101, a condensing lens 102 that condenses the light from the laser light source 101, a light guide fiber 103 in which a plurality of optical fibers are bundled, and a concentrator that condenses the laser light on lesion cells. An optical lens 104 is provided. As the laser light source 101, a laser light source that can output laser light under a condition that can selectively destroy lesion cells by ionization is used.

  A preferred laser light source 101 is a mode locked Ti: Sapphire laser. The mode locked Ti: Sapphire laser is suitable as the laser light source of this embodiment from the viewpoint of the characteristics of the output laser light or the control thereof. The pulse laser beam output from the laser light source 101 under a predetermined condition is condensed by the condenser lens 102 and enters the light guide fiber 103. The pulse laser beam is transmitted through the light guide fiber 103 and enters the condenser lens 104. The pulsed laser beam is condensed by a condenser lens 104 onto a lesion cell that is a target in the lesion 150.

  The illumination system includes an illumination light source 111, a light guide fiber 112, and an illumination lens 113. The illumination light source 111 includes an illumination lamp 114 such as a xenon lamp and a condensing lens 115. The light guide fiber 112 is formed by bundling a plurality of optical fibers, and transmits light from the illumination light source 111 to the lesion 150. The illumination lens 113 is disposed at the tip of the light guide fiber 112 and illuminates the lesion 150 over a wide range. The light from the illumination lamp 114 is collected by the condenser lens 115 and enters the light guide fiber 112. The illumination light is transmitted through the light guide fiber 112 and enters the illumination lens 113. The illumination lens 113 diffuses the incident light and irradiates the lesion 150 widely.

  The observation system of this embodiment uses a fiber scope. The observation system includes an objective lens 121 that forms an image of an object, an image guide fiber 122 serving as an image transmission system that transmits an image formed by the objective lens 121 to the rear part of the system, and an image guide fiber 122. The image processing device 123 converts the optical image transmitted by the method into an electrical signal and displays the image. The image processing device 123 enables observation of the lesion 150 by displaying the state of the lesion 150 on a monitor. Alternatively, the image data of the lesion 150 can be recorded on an optical / magnetic recording / reproducing apparatus (not shown).

  The image processing device 123 includes an image pickup unit 124 that converts an optical signal from the image guide fiber 122 into an electric signal, an image processing unit 125 that performs predetermined signal processing on the converted electric signal, and an image of the lesion unit 150. The monitor unit 126 includes a display for displaying. The imaging unit 124 may use a CCD (Charge Coupled Device) camera, a CMOS sensor, a photodiode array, or the like. The imaging unit 124 detects incident light from the image guide fiber 122, converts the incident light into a video signal according to the intensity, and transmits the video signal to the image processing unit 125.

  The image processing unit 125 performs necessary image processing on the received video signal, and transmits a signal for image display to the monitor unit 126. The monitor unit 126 displays the captured image on the display. An eyepiece device can be used instead of or in addition to the image processing device 123. As the observation system, other types of observation systems such as a rigid endoscope using a relay lens and a video endoscope using a solid-state imaging device and an electric signal line are used depending on the usage form of the laser treatment apparatus 100. can do. In addition, the laser treatment apparatus 100 supplies cleaning water and cleaning air to the distal ends of the laser irradiation light guide fiber 103, the irradiation light guide fiber 112, and the observation system image guide fiber 122. The fiber can be discharged and the tip of each fiber can be cleaned.

  A control unit 130 controls the laser treatment apparatus 100 by transmitting a control signal to each unit of the laser treatment apparatus 100. The control unit 130 includes a user / interface having an input / output unit, and performs setting for controlling each unit and control of each unit during operation according to input from the user or pre-registered registration data. be able to. For example, the control unit 130 can perform laser light output control from the laser light source 101 or set and control output conditions. Further, the user can perform ON / OFF or light amount control of the illumination light source 111 or editing and control of image data of the image processing device 123 via the control unit 130. The user refers to the image displayed on the monitor unit 126 and operates the setting of the irradiation position of the pulsed laser beam or the irradiation of the pulsed laser beam via the control unit 130, thereby causing the lesion. Department of treatment can be performed.

  FIG. 2 is a conceptual diagram showing a state of laser light irradiation in the lesion 150. FIG. The pulsed laser beam is condensed on the target lesion cell 210 by the condenser lens 104. The laser treatment apparatus 100 of this embodiment destroys the lesion cell 210 using multiphoton absorption. Multiphoton absorption, which is a nonlinear optical effect, can be caused by using an ultrashort pulse laser. In one-photon absorption, which is a linear optical effect, the entire region irradiated with laser light absorbs light energy. On the other hand, multiphoton absorption, which is a nonlinear optical effect, is caused only in the condensing part of the pulse laser beam because the occurrence probability is proportional to the power of the light intensity.

  By utilizing this characteristic, the focus cell 210 can be selectively destroyed by focusing the pulsed laser beam on the focus cell 210. In peripheral cell portions irradiated with laser light, such as before the condensing part or the rear part of the condensing part, multiphoton absorption is not induced by intracellular molecules because the photon density of the laser light is small. This is a great advantage compared to a laser treatment device that simultaneously destroys surrounding healthy cells including cells in front of lesion cells by thermal damage, such as a laser knife using a conventional YAG laser.

  The laser treatment apparatus 100 of this embodiment destroys lesion cells by ionizing molecules in the lesion cells. FIG. 3 is a diagram for explaining a process in which focal cells are destroyed by molecular ionization. In the focus cell, water and protein molecules are ionized by absorbing the energy of the pulsed laser beam by multiphoton absorption. Hereinafter, an ionization process using water molecules as an example and a cell destruction process using the water molecule will be described with reference to FIGS. 3 and 4.

  One process of ionization of water molecules by pulsed laser light irradiation is direct ionization by multiphoton ionization. When a continuous wave laser is used, a photon density sufficient for generating free electrons cannot be obtained by one-photon absorption. On the other hand, when the pulse laser beam is condensed and the photon density becomes a predetermined value or more, multiphoton absorption is induced. Ionization by multiphoton absorption is the key to ion generation by ultrashort pulse laser irradiation. FIG. 3A shows a process of ionization of one water molecule by multiphoton absorption. As shown in FIG. 3A, the water molecule in the n state absorbs the energy of the pulsed laser beam by multiphoton absorption, one of the bound electrons causes a state transition, and the water molecule transitions to the σ * state. .

  One of the bound electrons of the unshared electron pair absorbs the photon energy and becomes a quasi-free electron, so that the water molecule is ionized. Since the transition between the ground state and the free electron state of an electron requires a lot of energy, it usually does not occur with one-photon absorption when using wavelengths in the near infrared region. However, as shown in FIG. 4, when a plurality of photons are instantaneously absorbed by a molecule in a time as short as fluorescence emission or non-radiative transition time, electrons in the ground state of the molecule have energy corresponding to a band gap. And transition to the quasifree state. Quasi-free state electrons are not strongly bonded to the molecule.

  For this reason, the quasi-free state electrons repeat one-photon absorption through a process called reverse bremsstrahlung as shown in FIG. Quasi-free state electrons gain sufficient kinetic energy from the electric field due to inverse bremsstrahlung and collide with adjacent bound electrons to induce impact ionization of the bound electrons and excite the adjacent bound electrons to the quasi-free state. To do. In this way, ionization proceeds by the interaction between excited molecules and non-excited molecules. As shown in FIG. 4, when the quasi-free electron repeats one-photon absorption by inverse bremsstrahlung and absorbs k photons and the total energy amount becomes the size of the energy band gap, adjacent bound electrons and energy By sharing the quasi-free electrons can be newly generated.

  Generation of quasifree electrons by multiphoton ionization and generation of quasifree electrons by impact ionization are repeatedly induced by laser irradiation. In particular, as shown in FIGS. 3C and 4, when a large number of quasifree electrons repeat impact ionization, ionization is induced in a cascade (cascade ionization), and a large number of quasifree electrons are generated. The With cascade ionization, the quasi-free electrons increase with a power. Multiphoton absorption is induced even in the absence of quasifree electrons. Multiphoton ionization continues for the duration of the laser pulse and produces quasifree electrons that act as a “seed” for cascade ionization.

  These two ionization processes occur during laser pulse irradiation, and the ionization process depends on the laser pulse width and the physical properties of intracellular molecules. Absorption by reverse bremsstrahlung occurs depending on the presence of other particles. This is related to the fact that the cascade ionization process requires as much time as the average time that particles collide. When laser irradiation of a short time such as a femtosecond laser occurs, multiphoton absorption occurs predominantly in the cell. On the other hand, in the case of relatively long laser irradiation such as a picosecond laser, cascade ionization becomes dominant.

  By these ionization processes, the quasi-free electron density at the laser converging site is greatly increased, and when the quasi-free electron exceeds a predetermined density, plasma is generated at the condensing site of the laser beam. When plasma is formed, it leads to an enormous increase in energy absorption coefficient and causes rapid energy transfer from the electric field of laser light to molecules. This photodielectric breakdown destroys the molecular bonds of the protein, destroying the cell membrane or intracellular organelles. By the above process, the focal cells can be selectively destroyed.

The free electron density necessary for generating plasma varies depending on the wavelength of light, but is approximately 10 ²¹ cm ⁻³ (femtosecond / picosecond laser) and 10 ²⁰ cm ⁻³ (nanosecond laser). As described above, the cell destruction process of this embodiment is induced based on molecular ionization, unlike the lesion cell destruction by heat, so that the lesion cells are effectively prevented without causing thermal damage to surrounding cells. Can be selectively destroyed. Alternatively, molecular ionization has an excellent feature as a therapeutic device in that it can be induced without requiring a specific drug or dye.

  The laser treatment apparatus 100 of this embodiment is controlled so as to prevent unnecessary thermal damage of other cells while performing cell destruction by selectively ionizing lesion cells. The laser treatment apparatus 100 uses near infrared light as laser light, and preferably uses light having a wavelength of about 700 to about 900 nm. More preferably, light having a wavelength of about 750-850 nm is used. FIG. 5 shows an approximate relationship between the light absorption intensity of water and the wavelength of light. As shown in FIG. 5, water has a characteristic that light absorption is reduced in the vicinity of 800 nm. For this reason, by using laser light in the above-mentioned wavelength range, undesirable absorption of light energy and thermal damage by surrounding cells can be suppressed, and selective destruction of focal cells can be performed effectively.

  The laser treatment apparatus 100 uses pulsed laser light. Unlike continuous wave laser light, the energy density can be increased locally by pulsed laser light, so that ionization induced by multiphoton absorption can selectively destroy lesion cells in three dimensions. . By using the pulsed laser beam, it is possible to effectively select and destroy the lesion cells on which the laser beam is collected. The average intensity of the pulsed laser beam is several tens to several hundreds mW, but light having a very high intensity can be obtained in the light condensing part.

  The peak intensity of the pulse laser beam is preferably 10 kW or more under the condenser lens 104. More preferably, the peak intensity of the pulse laser beam is 15 kW or more, and most preferably 20 kW or more. The ionization process of intracellular molecules greatly depends on the peak intensity of the pulsed laser. Therefore, the peak intensity control of the pulse laser beam is important. In order to effectively destroy cells by ionization, a pulsed laser beam in the above range is used.

  Multiphoton ionization preferably performs absorption of three or more photons. Multiphoton absorption of three or more photons can reduce the energy of one photon for ionization. Thereby, it becomes possible to greatly reduce the damage caused by the one-photon absorption of the sample.

  The laser treatment apparatus 100 can destroy lesion cells by one laser pulse. It is possible to irradiate the lesion cell with a plurality of times of pulsed laser light and continue to irradiate the pulsed laser light after the cells are destroyed as long as no substantial problem occurs. However, since unnecessary laser light irradiation causes a thermal effect on surrounding cells, it is preferable to shorten the laser light irradiation time. Preferably, one pulse laser beam irradiation is applied to the lesion cell in the lesion site.

  The pulse width of the pulse laser beam is preferably 10 ps or less under the condenser lens 104. More preferably, a laser having a pulse width of 1 ps or less is used. In order to suppress thermal influences on other cells other than the lesion cells, it is necessary to use a pulsed laser beam having a small pulse width. In order to effectively ionize the lesion cells and not cause unnecessary damage to surrounding cells, it is necessary to irradiate pulsed light having a large peak intensity and a small pulse width.

  For this reason, the pulse width preferably has the above value. When transmitting pulsed laser light using the optical fiber 103 as in this embodiment, the output light from the laser light source 101 can be controlled so that the pulse width is about 1-10 ps. preferable. This is because the femtosecond pulse light propagates through the fiber and the pulse width is expanded to picoseconds, so that the necessary laser power cannot be obtained. In addition, in order for laser output to induce destruction by the ionization of a focus cell, the suitable conditions based on the said conditions are selected according to an object cell or an apparatus to be used.

  As described above, the laser treatment apparatus according to the present embodiment can selectively destroy lesion cells in a three-dimensional manner at the cell level by ionization of intracellular molecules. By utilizing cell destruction by ionization, there is no thermal damage to other cells, and it has a great advantage as a cell level therapeutic device.

It is a block diagram which shows schematic structure of a laser treatment apparatus. It is a conceptual diagram which shows the mode of irradiation of the laser beam to a lesion part. It is a figure explaining the ionization process of an intracellular molecule. It is a figure explaining the energy relationship of the ionization process of an intracellular molecule. It is a figure explaining the relationship between the light absorption intensity of water and a wavelength.

Explanation of symbols

DESCRIPTION OF SYMBOLS 100 Treatment apparatus, 101 Laser light source, 102 Condensing lens, 103 Light guide fiber, 104 Condensing lens, 111 Illumination light source, 112 Light guide fiber, 113 Illumination lens, 114 Illumination lamp, 115 Condensing Lens, 121 objective lens, 122 image guide fiber, 123 image processing device, 124 imaging unit, 125 image processing unit, 126 monitor unit, 130 control unit, 150 lesion unit

Claims (13)

A laser treatment device for destroying lesion cells,
A laser light source that outputs pulsed laser light;
Optical means for guiding the pulsed laser light to the lesion cell;
A control unit for controlling the laser light source,
The control unit controls the laser light source so that the lesion cells are destroyed by ionizing molecules due to multiphoton absorption in the lesion cells irradiated with the pulsed laser light. Therapeutic device.   The laser treatment apparatus according to claim 1, wherein the treatment apparatus destroys the lesion cell with one pulse of laser light.   The laser treatment apparatus according to claim 1, wherein plasma is generated by ionization of a plurality of molecules in the lesion cell, and a film forming the lesion cell is destroyed.   The laser treatment apparatus according to claim 3, wherein plasma is generated by the cascaded induction of ionization by molecular interaction in the lesion cell by the pulsed laser light irradiation.   3. The laser treatment apparatus according to claim 1, wherein the control unit controls the laser light source so that a peak energy of a pulsed laser beam applied to the lesion cell is 10 KW or more.   3. The laser treatment apparatus according to claim 1, wherein the control unit controls the laser light source so that a peak energy of pulsed laser light applied to the lesion cell is 20 KW or more.   The laser treatment according to claim 1, 2, 5, or 6, wherein the control unit controls the laser light source so that a pulse width of a pulse laser beam applied to the lesion cell is 10 ps or less. apparatus.   The laser treatment according to claim 1, 2, 5, or 6, wherein the control unit controls the laser light source so that a pulse width of a pulse laser beam applied to the lesion cell is 1 ps or less. apparatus. The optical means comprises an optical fiber for transmitting pulsed laser light;
The laser treatment apparatus according to claim 1, 2, 5, or 6, wherein the control unit controls the pulse width of the pulse laser beam output from the laser light source to be 1 ps or more and 10 ps or less.   The said control part controls the said laser light source so that the wavelength of the pulse laser beam irradiated to the said lesion cell is 700 nm or more and 900 nm or less, The 1, 2, 5, 6, 7, 8 Or the laser treatment apparatus according to 9.   The said control part controls the said laser light source so that the wavelength of the pulse laser beam irradiated to the said lesion cell is 750 nm or more and 850 nm or less, The 1, 2, 5, 6, 7, 8 Or the laser treatment apparatus according to 9.   The laser treatment apparatus according to claim 1, wherein the multiphoton absorption simultaneously absorbs three or more photons. A method for destroying focal cells by irradiating with pulsed laser light,
Irradiating a pulsed laser beam of the lesion cells;
Ionizing a plurality of molecules in the lesion cell due to multiphoton absorption;
And destroying the lesion cell by light absorption of the lesion cell having the plurality of ionized molecules.

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