Cancer cell killing tool and radiator for killing cancer cell

Abstract

Provided is a cancer cell killing tool having: a heat generating body; and a radiator in which a peak region, which is an absorption peak region or a transmission peak region, overlaps the absorption wavelength of cancer cells, and which radiates infrared light of the absorption wavelength upon receiving heat or radiant light generated by the heat generating body.

Description

Cancer cell killing devices and cancer cell killing radiators

[0001] The present invention relates to a cancer cell killing device and a radiator for killing cancer cells. The present invention claims priority from Japanese Patent Application No. 2024-148418 filed on August 30, 2024, and Japanese Patent Application No. 2025-022126 filed on February 14, 2025, and the contents of these applications are incorporated by reference into this application in designated states where incorporation by reference of documents is permitted.

[0002] Due to its highly malignant nature, cancer is a global health threat and one of the most serious challenges facing modern medicine. While cancer has long been considered extremely difficult to cure, many researchers and medical professionals have worked hard to understand its etiology and develop new treatments. As a result, the success rate of cancer treatment is improving every day, and the survival rate has also improved dramatically. However, there are still many challenges remaining, such as cases where the initial symptoms are mild and the disease is discovered late, or cases where treatment is difficult, known as intractable cancers.

[0003] Cancer treatments mainly include radiation therapy, immunotherapy, chemotherapy, and surgery, but these methods can cause serious side effects and treatment resistance. For example, radiation therapy irradiates cancer tissue with high-energy radiation to destroy it, which can also affect surrounding healthy tissue and cells. Furthermore, radiation therapy is also a concern as it poses a risk of secondary cancer due to radiation in the future.

[0004] Immunotherapy is a treatment that activates the immune system to attack cancer cells. It acts specifically on cancer cells, suppressing their impact on surrounding healthy tissue and promoting a sustained immune response, which is expected to prevent recurrence. However, immunotherapy has problems such as the risk of autoimmune disease and its ineffectiveness depending on the patient and type of cancer.

[0005] Chemotherapy is effective against many types of cancer because it delivers anticancer drugs throughout the body to destroy cancer cells, and some patients have even seen complete disappearance of cancer. However, due to side effects, there are concerns about a decline in the patient's quality of life (QOL), the risk of infection due to suppression of the immune system, the acquisition of resistance by cancer cells, and adverse effects on normal cells.

[0006] Surgery is an effective method for completely removing cancer and is highly effective for early-stage cancer, but there are challenges associated with the risks of the surgery itself, the risk of recurrence when the cancer metastasizes, and the risk of cancer that is not suitable for surgery.

[0007] The challenge common to all of these treatments is how to distinguish cancer tissue from normal tissue as much as possible and how to selectively treat it using each method without affecting normal tissue.

[0008] Meanwhile, hyperthermia has long been known as a treatment that can be expected to maintain quality of life. Recently, hyperthermia, a type of hyperthermia that attacks cancer cells with heat, has been attracting attention (Non-Patent Document 1). Cancer cells are more sensitive to heat than normal cells, and their growth and survival are suppressed when temperatures exceed approximately 42°C. Hyperthermia utilizes this phenomenon by applying high-frequency waves to cancer tissue to treat it. However, it is difficult to locally heat deep cancer tissue at the cellular level, and the large amount of total energy applied poses serious problems, such as thermal damage to surrounding normal cells and the surrounding diffusion of cancer cells.

[0009] Recently, oncothermia has emerged as a method for solving this problem (Patent Document 1). Because cancer cells require more glucose metabolism than normal cells, the ion concentration near the cancer cells increases, resulting in differences in electrical properties compared to the surrounding area. Focusing on these differences in electrical properties, oncothermia applies a weak electric field near the cancer cells, locally raising the temperature of the cancer cells and inhibiting their growth. This method uses less total energy than hyperthermia, which is expected to reduce the impact on surrounding normal tissue. However, it still requires the application of approximately 150 W of energy, and the impact on normal tissue remains unresolved, leaving the problem unresolved.

[0010] It is also known that cancer cells have different infrared absorption spectra compared to normal cells (Non-Patent Document 2), and the application of this to cancer diagnosis is being considered (Non-Patent Document 3).

[0011] EP 2174689

[0012] P. Wust, et al., "Hyperthermia in combined treatment of cancer," The Lancet Oncology, Vol. 3, p. 487, 2002. Takashi Ishiguro, "In situ infrared spectroscopy observation in water," [online], August 2016, [searched July 3, 2024], Internet, <URL: https: / / www. tus. ac. jp / ura / wp-content / uploads / 2016 / 08 / 20160901b. pdf>. K. Kochan, et al., "Comparison of FTIR transmission and transmission substrates for canine liver cancer detection," Analyst, Vol. 140, No. 7, p. 2402, 2015.

[0013] In one aspect, the present invention aims to induce apoptosis in cancer cells while reducing the effect on normal cells.

[0014] According to one aspect of the present invention, a cancer cell killing device comprises a heating element and a radiator whose peak region, which is an absorption peak region or a transmission peak region, overlaps with the absorption wavelength of cancer cells and which receives heat or radiant light generated by the heating element and radiates infrared light of the absorption wavelength.

[0015] In the cancer cell killing device, the radiator may include an optical film having the peak region.

[0016] In the cancer cell killing device, the optical film may be a laminated film in which a plurality of films made of different materials are laminated.

[0017] The cancer cell killing device may further comprise a filter onto which the infrared light is incident, the filter having a transmission peak region whose wavelength overlaps with the peak region.

[0018] In the cancer cell killing device, the radiator may be a plate having a first surface that receives the heat or the radiant light and a second surface that faces the first surface and radiates the infrared light.

[0019] In the cancer cell killing device, the heat generating element may be a heater provided at a distance from the first surface.

[0020] In the cancer cell killing device, the radiator may be in contact with the surface of the heat generating element.

[0021] In the cancer cell killing device, the heating element may be a tungsten plate or a tantalum plate.

[0022] In the cancer cell killing device, the heat generating element may be a granule, and the radiating element may be a coating covering the surface of the granule.

[0023] In the cancer cell killing device, the ratio of the infrared absorbance at the absorption wavelength of the cancer cells to the infrared absorbance at the absorption wavelength of the normal cells may be greater than a reference value.

[0024] In the above-mentioned cancer cell killing device, the absorption wavelength may be any one of 9548 nm or 9823 nm, which are the absorption wavelengths of liver cancer cells, 5734 nm, which are the absorption wavelengths of skin cancer cells, 6050 nm, which are the absorption wavelengths of breast cancer cells, and 10310 nm, which are the absorption wavelengths of uterine cancer cells.

[0025] In the cancer cell killing device, the full width at half maximum of the peak region may be 0.1 nm or more and 200 nm or less.

[0026] In the cancer cell killing device, the wavelength of the apex of the peak region may be located within a wavelength range of ±50 nm of the absorption wavelength.

[0027] In the cancer cell killing device, a plurality of absorption wavelengths may exist, and each of the plurality of absorption wavelengths may overlap with the peak region.

[0028] In the cancer cell killing device, the wavelength at the apex of the peak region may be an average wavelength of the plurality of absorption wavelengths.

[0029] According to another aspect of the present invention, a radiator for killing cancer cells has a peak region that is an absorption peak region or a transmission peak region that overlaps with the absorption wavelength of cancer cells, and radiates infrared light of the absorption wavelength upon receiving heat or radiant light.

[0030] The above-mentioned radiator for killing cancer cells may further comprise an optical film having the peak region.

[0031] In the above-mentioned radiator for killing cancer cells, the optical film may be a laminated film in which a plurality of films made of different materials are laminated.

[0032] The above-mentioned radiator for killing cancer cells may further comprise a plate having a first surface that receives the heat or the radiant light and a second surface that faces the first surface and radiates the infrared light.

[0033] In the above-mentioned radiator for killing cancer cells, the ratio of the infrared absorbance at the absorption wavelength of the cancer cells to the infrared absorbance at the absorption wavelength of normal cells may be greater than a reference value.

[0034] In the above-mentioned radiator for killing cancer cells, the absorption wavelength may be any one of 9548 nm or 9823 nm, which are the absorption wavelengths of liver cancer cells, 5734 nm, which are the absorption wavelengths of skin cancer cells, 6050 nm, which are the absorption wavelengths of breast cancer cells, and 10310 nm, which are the absorption wavelengths of uterine cancer cells.

[0035] In the above-mentioned radiator for killing cancer cells, the full width at half maximum of the peak region may be 0.1 nm or more and 200 nm or less.

[0036] According to the present invention, apoptosis in cancer cells can be induced while reducing the effect on normal cells.

[0037] FIG. 1 is a diagram showing the infrared absorption spectra of normal cells and liver cancer cells. FIG. 2 is a cross-sectional view of a cancer cell killing device according to the first embodiment. FIG. 3 is a cross-sectional view of a radiation emitter according to the first embodiment. FIG. 4 is a diagram showing an example of the thickness of each film of a first optical coating according to the first embodiment. FIG. 5 is a diagram showing an example of the thickness of a second optical coating according to the first embodiment. FIG. 6 is a cross-sectional SEM image of a first optical coating according to the first embodiment. FIG. 7 is an elemental mapping image of a first optical coating according to the first embodiment by EDX. FIG. 8 is a cross-sectional SEM image of a second optical coating according to the first embodiment. FIG. 9 is an elemental mapping image of a second optical coating according to the first embodiment by EDX. FIG. 10 is a diagram showing the measurement results of the transmission spectrum of a radiation emitter according to the first embodiment in the wavelength range of 9,300 nm to 10,000 nm, obtained for each film thickness shown in FIGS. 4 and 5. FIG. 11 shows the radiation spectra in the wavelength range of 3 μm to 25 μm of the heating element according to the first embodiment and the radiators obtained with the respective film thicknesses shown in FIGS. 4 and 5 . FIG. 12 shows the measurement results of the absorption spectrum of the filter according to the first embodiment. FIG. 13 is a cross-sectional view of one well of a 96-well well plate used in the first embodiment. FIG. 14 is an image of a well according to the first embodiment obtained by photography. FIG. 15 is a graph obtained by statistically processing the apoptotic cell rate according to the first embodiment. FIG. 16 is an image of a well according to the first embodiment, taken one hour after the start of culture following replacement of the growth medium with a medium supplemented with a caspase-3 activity detection reagent. FIG. 17 is an image of a well according to the first embodiment, taken six hours after the start of culture following replacement of the growth medium with a medium supplemented with a caspase-3 activity detection reagent. FIG. 18 is an image of a well according to the first embodiment, taken 24 hours after the start of culture following replacement of the growth medium with a medium supplemented with a caspase-3 activity detection reagent. Fig. 19 is a graph obtained by statistically processing the apoptotic cell rates calculated from Figs. 16 to 18. Fig. 20A is a cross-sectional view of a cancer cell killing instrument according to a second embodiment. Fig. 20B is a schematic diagram showing an example of a method of using the cancer cell killing instrument according to the second embodiment. Fig. 21 is a cross-sectional view of a cancer cell killing instrument according to a third embodiment. Fig. 22 is a diagram showing the transmission spectrum of a radiator according to a fourth embodiment.FIG. 23 is a diagram showing the infrared absorption spectra of normal cells and skin cancer cells in the fifth embodiment. FIG. 24 is a diagram (part 1) showing an example of the thickness of each film of the first optical coating when skin cancer is targeted in the fifth embodiment. FIG. 25 is a diagram (part 2) showing an example of the thickness of each film of the first optical coating when skin cancer is targeted in the fifth embodiment. FIG. 26 is a diagram showing an example of the thickness of each film of the second optical coating when skin cancer is targeted in the fifth embodiment. FIG. 27 is a diagram showing the infrared absorption spectra of normal cells and breast cancer cells in the fifth embodiment. FIG. 28 is a diagram (part 1) showing an example of the thickness of each film of the first optical coating when breast cancer is targeted in the fifth embodiment. FIG. 29 is a diagram (part 2) showing an example of the thickness of each film of the first optical coating when breast cancer is targeted in the fifth embodiment. FIG. 30 is a diagram showing an example of the thickness of each film of the second optical coating when breast cancer is targeted in the fifth embodiment. FIG. 31 is a diagram showing the infrared absorption spectra of normal cells, dysplastic cells, and uterine cancer cells in the fifth embodiment. Fig. 32 is a diagram (part 1) showing an example of the thickness of each film of the first optical film when uterine cancer is the target in the fifth embodiment. Fig. 33 is a diagram (part 2) showing an example of the thickness of each film of the first optical film when uterine cancer is the target in the fifth embodiment. Fig. 34 is a diagram showing an example of the thickness of each film of the second optical film when uterine cancer is the target in the fifth embodiment.

[0038] Hereinafter, an embodiment of the present invention will be described with reference to the drawings. Note that like elements are given like reference numerals and their description will be omitted.

[0039] First Embodiment In this embodiment, cancer cells are attacked while reducing the effect on normal cells by utilizing the fact that cancer cells exhibit absorption peaks at wavelengths different from those of normal cells.

[0040] Figure 1 shows the infrared absorption spectra of normal cells and liver cancer cells. The horizontal axis of Figure 1 represents the wave number of infrared light, and the vertical axis represents the absorbance of infrared light. Note that Figure 1 is an excerpt of a key portion from Non-Patent Document 2. Note that the infrared light in this embodiment includes not only near-infrared light with a wavelength of 760 nm or more and 3000 nm or less, but also far-infrared light with a wavelength of 3000 nm or more and 1,000,000 nm or less.

[0041] While normal cells generate energy through aerobic respiration, cancer cells such as those in liver cancer generate energy through anaerobic respiration (the Warburg effect). Due to these metabolic differences, the infrared absorption spectrum of cancer cells differs from that of normal cells.

[0042] In the case of liver cancer cells, a unique absorption peak P １ , P ２ appears. Absorption peak P １ , P ２ are the absorption wavelengths λ １ , λ ２ This peak corresponds to the absorption wavelength λ １ is 9548 nm, and the absorption wavelength λ ２ is 9823 nm.

[0043] Absorption wavelength λ １ It is believed that if infrared light of this wavelength range is irradiated onto liver cancer cells, the energy of the infrared light can induce apoptosis in the liver cancer cells. １ If it can be limited to a narrow range near the absorption wavelength λ １ This can reduce the effects of light of wavelengths other than the absorption wavelength λ ２ But the same is true.

[0044] In the visible light region, light with an extremely narrow wavelength range can be generated by a laser light source, but the absorption wavelength λ １ and absorption wavelength λ ２ There are almost no laser light sources that can emit far-infrared light that can be tuned to such wavelengths. Even if such a laser light source were developed in the future, the area that can be irradiated with laser light would be limited to an extremely narrow range, and it would be difficult to irradiate liver cancer cells with each absorption wavelength λ over a wide range.１ , λ ２ The present inventors have found that by using the following radiators, it is possible to irradiate infrared light at each absorption wavelength λ １ , λ ２ They found that it is possible to irradiate a wide area with infrared light and induce apoptosis in liver cancer cells that have spread widely.

[0045] FIG. 2 is a cross-sectional view of the cancer cell killing instrument according to the first embodiment.

[0046] The cancer cell killing device 1 is an instrument that kills cancer cells by irradiating infrared rays from inside or outside the body onto tissue S containing human cancer cells, and has a housing 2, a heating element 3, a fixing part 4, a cell 5, a radiator 6, a filter 7, and a rod 8.

[0047] The housing 2 is a metallic enclosure with an open end 2a.

[0048] The heating element 3 is a heater such as a carbon heater that generates heat and radiates infrared radiation C toward the opening end 2a, and is fixed to the housing 2 via a fixing portion 4. In this embodiment, a rod-shaped carbon heater is used, with its rear end 3c fixed to the fixing portion 4 and its front end 3b facing the opening 2a. The shape of the heating element 3 is not limited to a rod shape, and it may be plate-shaped or spiral-shaped.

[0049] In this example, λ in FIG. １ or λ ２ The temperature of the heating element 3 is controlled to 450° C. or higher and 700° C. or lower so that the heating element 3 radiates radiant light C in a wavelength range that includes the absorption wavelength of liver cancer cells such as liver cancer cells. When the heating element 3 is a carbon heater, the temperature of the heating element 3 can be controlled within the above temperature range by controlling the power supplied to the heating element 3 to 100 W or higher and 400 W or lower.

[0050] The fixed portion 4 is, for example, a base that fits into a socket (not shown) of the housing 2. A reflector 3a is provided around the fixed portion 4, and the radiant light C is reflected by the reflector 3a, enabling the radiant light C to be efficiently collected at the open end 2a.

[0051] The cell 5 is a ring-shaped member that holds the radiator 6 and the filter 7 and is fixed to the open end 2 a of the housing 2 .

[0052] The radiator 6 is an optical plate provided at a distance D of 0 cm to 100 cm from the tip 3b of the heating element 3, and has a peak region which is an absorption peak region or a transmission peak region which overlaps with the absorption wavelength of liver cancer cells. The absorption wavelength which overlaps with the peak region is λ １ and λ ２ In the following, the absorption wavelength λ １ The following describes an example in which the radiator 6 has a peak region overlapping with the peak region of the radiator 6. The reason why the lower limit of the distance D is set to 0 cm is that the radiator 6 may come into contact with the heating element 3 as long as the radiator 6 is not damaged. The reason why the upper limit of the distance D is set to 100 cm is that it is assumed that a large heating element 3 will be used.

[0053] According to Kirchhoff's law, the emissivity of the radiator 6 at a certain wavelength is equal to the absorptivity of the radiator 6 at that wavelength. １ When the radiator 6 has an absorption peak region overlapping with the absorption wavelength λ １ Therefore, the radiator 6 has a radiation peak region overlapping the absorption wavelength λ １ When the radiator 6 receives the radiant light C containing the absorption wavelength λ １ Nearby infrared light IR is radiated by the radiator 6. The detailed structure of the radiator 6 will be described later.

[0054] In particular, the absorption wavelength λ １ The radiator 6 transmits a part of the infrared light of wavelength λ １ When infrared light of wavelength λ is included, a part of the infrared light passes through the radiator 6. １ The intensity of the infrared light increases, and the infrared light IR can efficiently induce apoptosis in liver cancer cells. In particular, the carbon heater absorbs the radiation C at an absorption wavelength λ １ This is suitable for inducing apoptosis in cancer cells because it contains infrared light.

[0055] The principle by which the radiator 6 radiates infrared light IR is not limited to the above. For example, the radiator 6 receives heat generated by the heating element 3, and the radiator 6 itself is heated by this heat, thereby generating infrared light IR. In this case, the absorption wavelength λ １ The radiation C is emitted in a wavelength range including the absorption wavelength λ １ In this case, the heating element 3 is required to be able to heat the radiator 6, and the radiant light emitted by the heating element 3 has an absorption wavelength λ １ For example, the absorption wavelength λ １ When a lamp heater that does not radiate radiation of the wavelength λ is used as the heating element 3, the heating element 3 is provided in contact with the radiator 6, and the radiator 6 is heated, so that the absorption wavelength λ １ The radiator 6 radiates infrared light IR in a wavelength range including the wavelengths

[0056] Also, without using Kirchhoff's law, the absorption wavelength λ １ A bandpass filter having a transmission peak region overlapping with the wavelength λ may be used as the radiator 6. In this case, light of the radiated light C having a wavelength overlapping with the transmission peak region is transmitted through the radiator 6, and light of the absorption wavelength λ １ Infrared light IR in a wavelength range including the wavelengths of the radiators 6 is radiated from the radiators 6. As described above, there are two principles by which the radiators 6 radiate infrared light IR: radiation utilizing Kirchhoff's law and light transmission through a bandpass filter, and either of these may be adopted. In the following, the peak region of the radiators 6 refers to the absorption peak region of the radiators 6 when Kirchhoff's law is utilized, and refers to the transmission peak region of the radiators 6 when a bandpass filter is utilized.

[0057] The filter 7 is a filter onto which the infrared light IR is incident, and has a transmission peak region that overlaps with the peak region of the radiator 6. This allows the filter 7 to cut infrared light of wavelengths other than the transmission peak region.

[0058] The rod 8 is inserted into a support device (not shown), such as a pillar or a tripod, to fix the cancer cell killing instrument 1. The user may use the cancer cell killing instrument 1 while holding the rod 8, without inserting the rod 8 into such a support device.

[0059] According to such a cancer cell killing device 1, the absorption wavelength λ １ The heating element 3 radiates radiant light C in a wavelength range including the absorption wavelength λ １ The radiator 6 radiates infrared light IR in a narrow range including the absorption wavelength λ １ is an absorption wavelength specific to liver cancer cells and not present in normal cells. Therefore, when infrared light IR is irradiated onto tissue S containing liver cancer cells 9 and normal cells (not shown), the normal cells are transmitted by the infrared light IR and are hardly affected, whereas the liver cancer cells 9 absorb the infrared light IR, undergoing apoptosis and ultimately dying.

[0060] Furthermore, in this example, the radiator 6 is plate-shaped, so it can irradiate infrared light IR over a wide area, which is difficult to achieve with a laser light source. Therefore, by using an optical fiber or other device to guide infrared light IR to the liver cancer site inside the body, it is possible to induce apoptosis in liver cancer cells distributed over a wide area inside the body.

[0061] Next, a detailed description will be given of the structure of the radiator 6. In the following, a case where a bandpass filter utilizing optical interference by a multilayer film is used as the radiator 6 will be described as an example.

[0062] 3 is a cross-sectional view of the radiator 6 according to this embodiment. As shown in FIG. 3, the radiator 6 includes a substrate 10, a first optical film 11, and a second optical film 12.

[0063] The substrate 10 is a silicon substrate that transmits infrared radiation C (see FIG. 2 ) and has opposing first and second surfaces 10a and 10b. The shape and size of the substrate 10 are not particularly limited. For example, the substrate 10 is a disk having a diameter of 0.2 mm to 2000 mm in a planar view, and a thickness of, for example, 0.01 mm to 10 mm. The lower limit of the diameter of the substrate 10 is set to 0.2 mm because infrared light IR with a diameter smaller than this can be emitted from an optical fiber, thereby reducing the benefits of using the substrate 10. The upper limit of the diameter of the substrate 10 is set to 2000 mm because a diameter of this size allows infrared light IR to be irradiated to the entire front, back, and sides of a human body. The planar shape of the substrate 10 is not limited to a circle, and may be an ellipse, a rectangle, or other polygonal shape.

[0064] Furthermore, the material of the substrate 10 is not limited to silicon, and the substrate 10 may be made of a material that transmits the radiant light C in the infrared region, such as germanium. When the substrate 10 transmits the radiant light C, the radiant light C is included in the infrared light IR, and the intensity of the infrared light IR can be increased.

[0065] Silicon has a transmittance of 0.3% in both the wavelength range of 400 nm to 9000 nm and the wavelength range of 10000 nm to 12000 nm. Therefore, the radiator 6, even if it is only the silicon substrate without the optical films 11 and 12, functions as a bandpass filter that selectively transmits infrared light in the wavelength range longer than 9000 nm and shorter than 10000 nm.

[0066] Furthermore, by forming the optical films 11, 12 on both surfaces 10a, 10b of the substrate 10 as in this example, the stresses acting on the substrate 10 from the optical films 11, 12 cancel each other out, thereby suppressing warping of the radiator 6 due to stress. Note that if suppression of warping is not necessary, the first optical film 11 and the second optical film 12 may be formed on only one of the surfaces 10a, 10b of the substrate 10.

[0067] A laminated film is formed on the first surface 10a of the substrate 10 as the first optical film 11. The laminated film is not particularly limited as long as it is a film in which a plurality of films made of different materials are laminated. In this example, a laminated film in which Ge (germanium) films 11x and ZnS (zinc sulfide) films 11y are alternately laminated is used as the first optical film 11. The surface of the first optical film 11 also functions as a first surface 6a that receives heat or radiant light C (see FIG. 2 ) generated by the heating element 3. Note that instead of a laminated film, a film having an absorption wavelength λ 1 is formed by the heat or radiant light C generated by the heating element 3. １ A single layer film of a material that emits infrared light may be used as the first optical film 11. This also applies to the second optical film 12 described below.

[0068] On the other hand, the second optical film 12 is a laminated film formed on the second surface 10b. As with the first optical film 11, the laminated film is not particularly limited as long as it is a film formed by stacking multiple films made of different materials. In this example, a laminated film formed by alternately stacking Ge films 12x and ZnS films 12y is used as the second optical film 12. The surface of the second optical film 12 functions as the second surface 6b that radiates infrared light IR (see FIG. 2).

[0069] In such a radiator 6, since the substrate 10 and the films 11x, 11y, 12x, and 12y are made of different materials, their refractive indices with respect to the radiated light C are also different from one another, and the radiated light C interferes inside the radiator 6. By controlling the thickness of the substrate 10 and the films 11x, 11y, 12x, and 12y, the absorption wavelength λ １ As a result, when the radiator 6 receives the radiant light C, the absorption wavelength λ １ The radiator 6 radiates coherent infrared light IR in a very narrow wavelength range including

[0070] As mentioned above, the absorption wavelength λ １The thicknesses of the substrate 10 and the films 11x, 11y, 12x, and 12y that can transmit light can be calculated using, for example, TFCalc (Thin Film Calculator), an optical design program manufactured by HULINKS, Inc. An example of the thicknesses of the films 11x, 11y, 12x, and 12y calculated using the optical design program when a silicon substrate with a thickness of 1 mm is used as the substrate 10 will be described with reference to FIGS.

[0071] FIG. 4 is a diagram showing an example of the thickness of each film 11x, 11y of the first optical film 11 according to this embodiment. In FIG. 4, "layer number" is a number assigned to each film 11x, 11y in order of proximity to the first surface 10a. In addition, "Ge" in "material" indicates the Ge film 11x, and "ZnS" indicates the ZnS film 11y. To make it easier to distinguish between "Ge" and "ZnS," the "Ge" row is hatched in FIG. 4. This also applies to FIGS. 24, 25, 28, 29, 32, and 33 of the fifth embodiment, which will be described later.

[0072] In the example of FIG. 4, the Ge film 11x and the ZnS film 11y each have 38 layers, and the total number of layers in the first optical film 11 is 76 layers.

[0073] FIG. 5 is a diagram showing an example of the thickness of each film 12x, 12y of the second optical film 12 according to this embodiment. In FIG. 5, "layer number" is a number assigned to each film 12x, 12y in order of proximity to the second surface 10b. Furthermore, "Ge" in "material" indicates the Ge film 12x, and "ZnS" indicates the ZnS film 12y. As in FIG. 4, the "Ge" row is hatched in FIG. 5 to make it easier to distinguish between "Ge" and "ZnS." This also applies to FIGS. 26, 30, and 34 of the fifth embodiment, which will be described later.

[0074] In the example of FIG. 5, the Ge film 12x and the ZnS film 12y each have nine layers, and the total number of layers in the second optical film 12 is 18 layers.

[0075] FIG. 6 is a cross-sectional SEM (Scanning Electron Microscope) image of the first optical film 11 according to this embodiment.

[0076] As shown in FIG. 6, the SEM image shows shading due to the difference in material between the Ge film 11x and the ZnS film 11y.

[0077] FIG. 7 is an element mapping image of the first optical film 11 according to this embodiment, obtained by EDX (Energy Dispersive X-ray Spectroscopy).

[0078] As shown in FIG. 7, the bright areas indicating the presence of C (carbon) and Si (silicon) are hardly present in the first optical film 11.

[0079] On the other hand, bright areas representing the elements S (sulfur), Zn (zinc), and Ge (germanium) appear in the first optical film 11. In particular, the positions of the bright areas of S and Zn coincide, confirming that a ZnS film is formed in the first optical film 11. It was found that interdiffusion near the interface between the ZnS film and the Ge film is small, and a good multilayer film of the ZnS film and the Ge film is obtained.

[0080] Fig. 8 is a cross-sectional SEM image of the second optical film 12 according to the present embodiment. As shown in Fig. 8, similar to the first optical film 11 in Fig. 6, shading due to the difference in materials between the Ge film 12x and the ZnS film 12y appears in the SEM image.

[0081] FIG. 9 is an element mapping image of the second optical film 12 according to this embodiment by EDX.

[0082] As shown in FIG. 9, the bright areas indicating the presence of C and Si are hardly present in the second optical film 12.

[0083] On the other hand, bright areas representing the elements S, Zn, and Ge appear in the second optical film 12. In particular, the positions of the bright areas of S and Zn coincide, confirming that a ZnS film is formed in the second optical film 12. It was found that interdiffusion near the interface between the ZnS film and the Ge film is small, and a good multilayer film of the ZnS film and the Ge film is obtained.

[0084] Fig. 10 shows the measurement results of the transmission spectrum of the radiator 6 according to this embodiment in the wavelength range of 9,300 nm to 10,000 nm, obtained for each of the film thicknesses shown in Figs. 4 and 5. The horizontal axis of Fig. 10 indicates the wavelength of light incident on the radiator 6, and the vertical axis indicates the transmittance of that light. The transmission spectrum was measured using a Lumos II FTIR (Fourier Transform Infrared Spectroscopy) spectrometer manufactured by Bruker Corporation. The thickness of the substrate 10 was 1 mm.

[0085] As shown in FIG. 10, the transmission spectrum of the radiator 6 has an absorption wavelength λ １ The transmission peak region 20 is a peak-shaped region in the absorption spectrum that includes a wavelength at which the transmittance is maximized.

[0086] In this example, by adopting the film thicknesses shown in FIGS. 4 and 5, the wavelength at the apex Q of the transmission peak region 20 becomes 9512 nm, and the absorption wavelength λ １ A transmission peak close to (=9548 nm) could be obtained.

[0087] The full width at half maximum Δλ of the transmission peak region 20 is preferably 0.1 nm or more and 200 nm or less. １ This can reduce the effects of light having a wavelength significantly different from the wavelength of light emitted from the radiator 6, such as the death of normal cells. On the other hand, the reason why the lower limit of the full width at half maximum Δλ is set to 0.1 nm is because the minimum full width at half maximum obtained by interference of the radiant light C in the radiator 6 is considered to be 0.1 nm. For the same reason, even in the radiator 6 utilizing Kirchhoff's principle, it is preferable to set the full width at half maximum Δλ in the absorption peak region of the radiator 6 to 0.1 nm or more and 200 nm or less.

[0088] In addition, the wavelength at the apex Q of the transmission peak region 20 and the absorption wavelength λ １ does not necessarily have to coincide with the absorption wavelength λ １ The wavelength range of ±50 nm is set to ±50 nm because if the peak Q is located in this range, the absorption wavelength λ 1 is strong enough to attack liver cancer cells. １This is because infrared light of wavelength λ is radiated from the radiator 6. For the same reason, the radiator 6 utilizing Kirchhoff's principle also has an absorption wavelength λ １ It is preferable to position the peak of the absorption peak region within a wavelength range of ±50 nm.

[0089] Fig. 11 is a diagram obtained by measuring the radiation spectrum in the wavelength range of 3 µm to 25 µm of the heating element 3 according to this embodiment and the radiator 6 obtained with each of the film thicknesses shown in Figs. 4 and 5. In this example, a carbon heater manufactured by Shimanuki Electric Co., Ltd. was used as the heating element 3. A Nicolet iS50 FTIR spectrometer manufactured by Thermo Fisher Scientific was used to measure the radiation spectrum.

[0090] As shown in FIG. 11, the radiator 6 has an absorption wavelength λ １ The radiator 6 has a radiation peak region 30 corresponding to the transmission peak region 20 (see FIG. 10 ) in the vicinity of the radiation peak region 30. Furthermore, the radiator 6 has a radiation region 31 in the range of 13 μm or more in addition to the radiation peak region 30. The radiation region 31 is a region in the radiation spectrum of the radiator 6 that has a finite intensity of emissivity, and its wavelength overlaps with the wavelength of the radiant light emitted by the heating element 3.

[0091] The radiation light in the radiation region 31 has a wavelength of absorption wavelength λ １ Since the radiation intensity is significantly different from the normal value, it hardly contributes to apoptosis of liver cancer cells 9 contained in tissue S (see FIG. 2 ). Furthermore, it is thought that irradiation of normal cells with the radiated light in radiation region 31 may have some effect on the normal cells. Therefore, in this embodiment, the radiated light in radiation region 31 is cut off by filter 7.

[0092] FIG. 12 shows the measurement results of the absorption spectrum of the filter 7 according to this embodiment. The vertical axis on the left side of FIG. 12 indicates the absorbance of the filter 7, and the horizontal axis indicates the wavelength. The absorbance can be easily converted to transmittance using the Beer-Lambert law; for example, an absorbance of 1 corresponds to a transmittance of 10%. Here, an Alpha Seal (Black) manufactured by Perkin-Elmer was used as the filter 7. A Lumos II FTIR spectrometer manufactured by Bruker Corporation was used to measure the absorption spectrum. Note that FIG. 12 also shows the emissivity of the radiator 6. The vertical axis on the right side of FIG. 12 indicates the emissivity.

[0093] As shown in Fig. 12, the filter 7 has a transmission peak region 22 whose wavelength overlaps with the transmission peak region 20 of the radiator 6. The transmission peak region 22 is an inverted peak region that includes wavelengths where the absorbance is minimal in the absorption spectrum of the filter 7. In the example of Fig. 12, the minimal wavelength in the transmission peak region 22 is approximately 9500 nm, which overlaps with the peak region 20 (see Fig. 10). With the wavelengths of the peak regions 20 and 22 overlapping in this way, the filter 7 can absorb the infrared light IR radiated by the radiator 6 at an absorption wavelength λ １ While selectively transmitting light in the vicinity of the absorption wavelength λ １ This allows the absorption wavelength λ １ This means that light with a significantly different wavelength can be prevented from affecting normal cells.

[0094] In this example, the filter 7 has an absorption peak region 23 whose wavelength overlaps with the radiation region 31 of the radiator 6. The absorption peak region 23 has a maximum point in the vicinity of 13.5 μm, which is about twice as high as the minimum point of the radiation region 31. Therefore, the filter 7 has an absorption wavelength λ １ The intensity of the radiation light in the 13.5 μm to 14.5 μm wavelength range is reduced to approximately 1 / 10 of that of the radiation light in the 13.5 μm to 14.5 μm wavelength range (= 9548 nm). ２ can be attenuated to

[0095] <Apoptosis Induction Evaluation> Next, apoptosis induction evaluation using the cancer cell killing device 1 according to this embodiment will be described.

[0096] In this evaluation, the human hepatoma-derived cell line HepG2 was used. The cells were incubated in a T75 flask using a growth medium and then incubated under CO ２ Incubator (37°C, 5% CO ２ The cells were cultured at 4°C / 100°F (100°C, ...

[0097] 13 is a cross-sectional view of one well of the 96-well plate used in this embodiment. The well plate 15 is a black-type plate made of polystyrene with a black pigment added, and has wells 15a formed therein. Growth medium 16 is poured into well 15a, and human hepatoma-derived cell line HepG2 cells are seeded therein as hepatoma cells 17.

[0098] The day after seeding, the medium was replaced with Hoechst 33342-containing medium for nuclear staining, and ２ The plate was incubated in an incubator for 30 minutes. After that, the Hoechst 33342-containing medium was replaced with a growth medium. For comparison, a non-irradiated sample was also prepared. The non-irradiated plate was once cooled to 50°C. ２ Returned to the incubator.

[0099] Each sample was then irradiated with coherent infrared light IR obtained from the cancer cell killing device 1. A silicon substrate with a thickness of 1 mm and a diameter of 166 mm was used as the substrate 10 (see Figure 3) provided in the cancer cell killing device 1. The materials and thicknesses of the optical films 11, 12 (see Figure 3) on both sides of the substrate 10 were as shown in Figures 4 and 5 above. In addition, 250 W of power was supplied to the heating element 3, heating the heating element 3 to 560°C.

[0100] To measure the intensity of the infrared light IR, an optical power meter was installed at a distance of 30 mm from the second surface 6b (see FIG. 3) of the radiator 6. The optical power meter was an Ophir L50 (150) A manufactured by Ophir Japan Co., Ltd. Then, as a warm-up for the heating element 3, which is a carbon heater, the intensity of the infrared light IR was measured 30 minutes after starting to energize the heating element 3. As a result of the measurement, the intensity of the infrared light IR was 0.59 W. This corresponds to an intensity per unit area of ​​30 mJ / scm. ２ This corresponds to 1.4 × 10 photons. １８ pieces / cm ２ is.

[0101] As shown in the following paper 1, the penetration depth of infrared light IR into water is about 20 μm, and in regions shallower than this, almost all of the infrared light IR is converted into heat.

[0102] (Paper 1) G. Hale, et al., “Optical Constants of Water in the 200-nm to 200-μm Wavelength Region”, Applied optics, Vol. 12, p. 555, 1973.

[0103] Therefore, when infrared light IR is irradiated onto liver cancer cells 17 from the bottom of well plate 15, the water in growth medium 16 is heated, making it difficult to determine whether the apoptosis of liver cancer cells 17 is caused by the heating of the water or by the irradiation of infrared light IR.

[0104] Therefore, infrared light IR was irradiated from the top surface of the well plate, where the irradiation intensity is extremely weak, and the infrared light IR was scattered and transmitted through the polystyrene that constitutes the well plate 15, thereby irradiating the liver cancer cells 17 with infrared light IR while suppressing heating of the water. As stated in the following paper 2, the transmittance of polystyrene to infrared light IR is 67%.

[0105] (Paper 2) M. Coustet and 1 other author, "Functionalization of styrene polymer through acylation and grafting under microwave energy," Polymer Journal, Vol. 43, p. 265, 2011

[0106] Therefore, only very weak scattered infrared light (IR) was irradiated onto the liver cancer cells 17. The fluorescent lights in the room were turned off during the experiment. Furthermore, as mentioned above, the influence of light irradiation was minimized by using a black well plate 15.

[0107] Furthermore, the cancer cell killing device 1 (see Figure 2) itself was not provided with a filter 7, but instead half of the 96-well well plate 15, or 48 wells, were covered with the filter 7. The remaining 48 wells were not covered with the filter 7, and the difference in effect depending on whether or not the filter 7 was present was also verified.

[0108] Furthermore, the distance between the upper surface 15b of the well plate 15 and the surface of the radiator 6 was set to 100 mm, and the irradiation time of the infrared light IR was set to 60 minutes.

[0109] After irradiation, the growth medium 16 was replaced with a medium containing a caspase-3 activity detection reagent (CellEvent Green Detection Reagent manufactured by Invitrogen), and the cells were incubated under CO ２ At this time, the 4-TBP-treated group was cultured in an incubator. The medium was replaced with a caspase-3 activity detection reagent containing an apoptosis inducer. ２ The cells were cultured in an incubator.

[0110] Then, at 1 hour, 6 hours, and 24 hours after the start of culture, images were taken of 25 fields per well using a 20x lens using a high-throughput, high-content imaging system (Opera Phoenix Plus, manufactured by Revvity).

[0111] Figure 14 shows images of wells according to this embodiment obtained by photography. In Figure 14, "non-irradiated" indicates wells that were not irradiated with infrared light IR, and "irradiated" indicates wells that were irradiated with infrared light IR. Furthermore, "untreated" indicates wells that were not replaced with a medium containing a caspase-3 activity detection reagent. Furthermore, "4-TBP" indicates wells that were replaced with a medium containing a caspase-3 activity detection reagent.

[0112] Furthermore, "without filter" indicates wells that were not covered with filter 7, and "with filter" indicates wells that were covered with filter 7.

[0113] At "1 hour later," "6 hours later," and "24 hours later," the growth medium 16 was replaced with a medium containing a caspase-3 activity detection reagent, and CO ２ The time elapsed since the start of culture in the incubator is shown.

[0114] In each image in Figure 14, white dots indicate the nuclei of liver cancer cells 17 stained with Hoechst 33342. The nuclei of liver cancer cells 17 in which apoptosis has not been induced are stained blue by Hoechst 33342, whereas the nuclei of liver cancer cells 17 in which apoptosis has been induced are stained green by Caspase-3.

[0115] Therefore, image analysis was performed on each image in Figure 14 using the Harmony Software included with the aforementioned Opera Phoenix Plus. Stained nuclei in the image were counted regardless of color, and this value was used as the total cell number. Among these, nuclei overlapping with the area stained green with caspase-3 were counted, and this value was used as the number of cells with caspase-3 activity detected. The number of cells with caspase-3 activity detected relative to the total cell number was used for evaluation as the apoptotic cell rate.

[0116] Figure 15 is a graph obtained by statistically processing the apoptotic cell rate. The meanings of the items on the horizontal axis in Figure 15 are the same as those of "untreated," "4-TBP," "no filter," and "filtered" in Figure 14. In this statistical processing, a Tukey-Kramer test was performed, with a significance level of 5% on both sides. Groups marked with the symbol "a" in Figure 15 indicate no significant difference. Error bars indicate standard error. ** indicates a significant difference obtained by Student's t-test.

[0117] As shown in Figure 15, a slight difference in the apoptotic cell rate was observed between the "untreated" and "4-TBP" treatments at the measurement time point of 1 hour, but a clear significant difference was observed at the measurement time points of 6 and 24 hours. These results confirmed that apoptosis could be detected using caspase-3 activity as an indicator.

[0118] On the other hand, when comparing "untreated," "with filter," and "without filter," there was no statistically significant difference in the apoptotic cell rate after 1 hour, 6 hours, or 24 hours. This indicates that it is difficult to induce apoptosis in liver cancer cells 17 when the infrared light IR irradiation time is 60 minutes and the distance between the upper surface 15b of well plate 15 and the surface of radiator 6 is 100 mm.

[0119] Therefore, a similar experiment was conducted under conditions in which the irradiation intensity of infrared light IR onto liver cancer cells 17 was further increased. Under these conditions, the irradiation time of infrared light IR was set to 120 minutes, and the distance between the upper surface 15b of well plate 15 (see FIG. 13) and the surface of radiator 6 was set to 30 mm. In addition, the cell density per well was increased from 10,000 cells / 0.1 mL to 50,000 cells / 0.1 mL. The remaining experimental procedures were the same as those in the experiments shown in FIGS. 14 and 15 .

[0120] Figures 16 to 18 show images of wells taken 1 hour, 6 hours, and 24 hours after the growth medium 16 in this experiment was replaced with a medium containing a caspase-3 activity detection reagent and culturing was initiated. The meanings of the items "non-irradiated," "irradiated," "untreated," "4-TBP," "no filter," and "filtered" in Figures 16 to 18 are the same as those in Figure 14. Images of five different wells were taken for each of these items.

[0121] Figure 19 is a graph obtained by statistically processing the apoptotic cell rates calculated from Figures 16 to 18. The meaning of the horizontal axis in Figure 19 is the same as in Figure 15, so its explanation will be omitted. As in Figure 15, this statistical processing was performed using the Tukey-Kramer test, with a significance level of 5% on both sides. In Figure 15, groups marked with the symbol "b" indicate no significant difference. Furthermore, "ab" indicates no significant difference between group "a" and group "b." The meaning of "**" is the same as in Figure 15.

[0122] As shown in Figure 19, a clear and significant difference was observed between "untreated" and "4-TBP" at each measurement time point: 1 hour, 6 hours, and 24 hours. These results confirmed that apoptosis could be detected using caspase-3 activity as an indicator in this experiment as well.

[0123] Furthermore, the apoptotic cell rate without filter was statistically significantly higher than that of untreated at all measurement times: 1 hour, 6 hours, and 24 hours. Similarly, the apoptotic cell rate with filter was statistically significantly higher than that of untreated at all measurement times: 1 hour, 6 hours, and 24 hours.

[0124] From these results, it was confirmed that irradiation with infrared light IR induces apoptosis in liver cancer cells 17.

[0125] To confirm that the occurrence of apoptosis was not due to an increase in the temperature of the growth medium 16 (see Figure 13), the temperatures of the growth medium 16 (see Figure 13) in each well (without filter and with filter) were measured immediately after irradiation with infrared light IR. The measurements were performed using two types of thermometers: a thermocouple thermometer and a radiation thermometer.

[0126] As a result of the measurement, it was confirmed that in the "no filter" case, the highest temperature among the 96 wells was 37.1°C, which did not reach the 42-43°C temperature used in hyperthermia cancer treatment. This confirmed that the cause of the onset of apoptosis was not the rise in temperature of the growth medium 16, but the irradiation of infrared light IR.

[0127] On the other hand, when the filter was present, the highest temperature among the 96 wells was 34.9°C, which was even lower than when the filter was absent. This is because when the filter 7 was present, the total energy of the infrared light IR irradiated onto the liver cancer cells 17 was lower than when the filter 7 was absent, and the temperature rise of the growth medium 16 was suppressed.

[0128] When comparing the "without filter" and "with filter" cases after 24 hours, the "with filter" case tends to have a higher apoptotic cell rate than the "without filter" case. As mentioned above, the temperature is kept lower in the "with filter" case than in the "with filter" case. Despite this, the apoptotic cell rate increased in this way, suggesting that the induction of apoptosis is not due to the heating of the liver cancer cells 17, but due to the absorption wavelength λ １ It was confirmed once again that the cause was the irradiation of liver cancer cells 17 with infrared light IR containing

[0129] This allows the absorption wavelength λ １ It was found that the filter 7 cutting infrared light IR with wavelengths significantly different from 9548 nm (=9548 nm) was effective in inducing apoptosis of liver cancer cells 17.

[0130] As described above, according to this embodiment, it has been confirmed that apoptosis of liver cancer cells 17 can be induced by the infrared light IR emitted by the radiator 6. As a result, human cancer can be treated by irradiating the affected area of ​​a human, including cancer tissue, with infrared light IR. Cancer in animals other than humans can also be treated by irradiating the affected area with infrared light IR. This also applies to the second to fifth embodiments described below.

[0131] In particular, the cancer cell killing device 1 can be assembled using simple components, namely, the heating element 3 such as a heater and the radiator 6, and therefore can be mass-produced at low cost.

[0132] Second Embodiment In this embodiment, a cancer cell killing device that emits infrared light IR inside the human body will be described.

[0133] Fig. 20A is a cross-sectional view of the cancer cell killing instrument 1 according to this embodiment. In Fig. 20A, the same elements as those described in the first embodiment are denoted by the same reference numerals, and their description will be simplified.

[0134] As shown in Figure 20A, the cancer cell killing device 1 comprises a heating element 3 and a radiator 6 provided in contact with the surface 3d of the heating element 3. The heating element 3 is made of particles such as magnetic nanoparticles or gold nanoparticles that generate heat when irradiated with microwaves. Among these, the material of the magnetic nanoparticles is iron oxide (Fe ３ O ４ , γ-Fe ２ O ３ ) and cobalt ferrite (CoFe ２ O ４ ) The particle size of the heating element 3 is not particularly limited, and can be, for example, 1 nm or more and 200 mm or less. The reason why the lower limit of the particle size is set to 1 nm is that it is difficult to produce particles with a particle size smaller than this. The reason why the upper limit of the particle size is set to 200 mm is that it is difficult to introduce particles with a particle size larger than this into the human body. Furthermore, the heating element 3 is not limited to a spherical shape, and may be an ellipsoid.

[0135] The radiator 6 is a coating that covers the entire surface of the heating element 3. For example, a laminated film such as the first optical film 11 and the second optical film 12 described in the first embodiment can be used as the radiator 6. By adjusting the material and thickness of each film that constitutes the laminated film, the absorption wavelength λ can be adjusted in the same way as in FIG. 10 of the first embodiment. １ appears in the transmission spectrum of the radiator 6, and the radiator 6 functions as a band-pass filter.

[0136] An example of a method for forming a film on the granular heating element 3 is the method described in International Publication No. 2017 / 126150. In this method, a film is coated on the surface of the heating element 3 by a sputtering method while rotating a cage containing the granular heating element 3. By performing this sputtering method multiple times while changing the target material, a laminated film in which multiple films made of different materials are stacked, such as the first optical film 11 and the second optical film 12, can be obtained.

[0137] When using this cancer cell killing device 1, first, microwaves are irradiated to heat the heating element 3 to a temperature of 40°C or higher and 800°C or lower. This causes the radiator 6 to be heated by heat conduction from the heating element 3 to the radiator 6. As a result, the radiator 6 absorbs the radiation of wavelength λ １ The radiation C is emitted in a wavelength range including the absorption wavelength λ １ The radiator 6 radiates infrared light IR in a narrow range including the wavelengths.

[0138] Instead of using a bandpass filter as the radiator 6, a radiator 6 utilizing Kirchhoff's law may be used. For example, by adjusting the material and thickness of each film constituting the first optical film 11 and the second optical film 12, the absorption wavelength λ １ By making the absorption peak region including the absorption wavelength λ appear in the absorption spectrum of the radiator 6, １ The radiator 6 radiates infrared light IR in a narrow range including the wavelengths.

[0139] In particular, in this example, the radiator 6 is in contact with the surface 3d of the heating element 3, so heat is efficiently conducted from the heating element 3 to the radiator 6. As a result, the radiator 6 is efficiently heated, and infrared light IR can be generated according to Kirchhoff's law.

[0140] Figure 20B is a schematic diagram showing an example of how to use this cancer cell killing device 1. In the example of Figure 20B, the cancer cell killing device 1 is delivered into the human body using an appropriate means such as an endoscope or drug delivery device. Microwaves are then irradiated onto the cancer cell killing device 1 from outside the human body, causing the heating element 3 (see Figure 20A) to heat up. As a result, infrared light IR is emitted from the cancer cell killing device 1 as described above, and this infrared light IR can induce apoptosis in liver cancer cells inside the human body.

[0141] According to the present embodiment described above, by using granular heating element 3, it is possible to easily transport cancer cell killing instrument 1 inside the human body as described above. Moreover, because infrared light IR is radiated in all directions by cancer cell killing instrument 1, there is no need to adjust the orientation of cancer cell killing instrument 1 so that liver cancer cells inside the human body are irradiated with infrared light IR, and liver cancer cells can be easily irradiated with infrared light IR.

[0142] (Third Embodiment) In this embodiment, a compact cancer cell killing device in which the heating element 3 and the radiating element 6 are integrated will be described.

[0143] Fig. 21 is a cross-sectional view of the cancer cell killing instrument 1 according to this embodiment. As shown in Fig. 1, this cancer cell killing instrument 1 has a heating element 3 and a radiator 6 provided in contact with the surface 3d of the heating element 3.

[0144] The heating element 3 is a plate that generates heat when electricity is applied, such as a tungsten plate or a tantalum plate. These materials have excellent heat resistance, which can enhance the heat resistance of the heating element 3. The thickness of the heating element 3 is not particularly limited, and can be, for example, 0.1 mm or more and 50 mm or less. The reason why the lower limit of the thickness is set to 0.1 mm is that if the thickness is thinner than this, the heating element 3 will easily bend, which could damage the films that make up the radiator 6. The reason why the upper limit of the thickness is set to 50 mm is that if the thickness is thicker than this, the weight of the cancer cell killing device 1 will increase, making it difficult to hold.

[0145] Furthermore, the heating element 3 in plan view is, for example, a circle with a diameter of 1 mm or more and 2000 mm or less. The reason why the lower limit of the diameter is set to 1 mm is because a diameter of this magnitude is required at least to irradiate a localized area of ​​a human body with infrared light IR. The reason why the upper limit of the diameter is set to 2000 mm is because a diameter of this magnitude allows infrared light IR to be irradiated to the entire front, back, side, and other surfaces of a human body. The planar shape of the heating element 3 is not limited to a circle, and may be an ellipse or a polygonal shape such as a rectangle.

[0146] The radiator 6 is an optical film formed in contact with the surface 3d of the heat generating element 3, and is a laminated film in which a plurality of films 6x and 6y made of different materials are laminated. The material and thickness of each film 6x and 6y are determined based on the absorption wavelength λ of liver cancer cells. １ The radiator 6 is set to have a transmission peak region 20 (see FIG. 10) that overlaps with the peaks.

[0147] When using this cancer cell killing device 1, the heating element 3 is energized to heat it to a temperature of 40°C or higher and 1000°C or lower. As a result, the radiator 6 is heated by the heat from the heating element 3. As a result, the radiator 6 absorbs light of wavelength λ １ The radiation C is emitted in a wavelength range including the absorption wavelength λ １ The radiator 6 radiates infrared light IR in a narrow range including the wavelengths.

[0148] According to the present embodiment described above, the radiator 6 is arranged so as to be in contact with the surface 3d of the heating element 3, thereby eliminating the space between the heating element 3 and the radiator 6 and making the cancer cell killing device 1 compact.

[0149] Furthermore, since the radiator 6 contacts the surface 3d of the plate-shaped heating element 3 over a wide area, heat is efficiently conducted from the heating element 3 to the radiator 6, and the radiator 6 can be efficiently heated to generate infrared light IR.

[0150] Furthermore, since the heating element 3 is plate-shaped, infrared light IR can be irradiated over a wide area, making it possible to induce apoptosis in liver cancer cells distributed over a wide area.

[0151] The principle by which the radiator 6 radiates infrared light IR may be either radiation using Kirchhoff's law or light transmission through a band-pass filter.

[0152] Fourth Embodiment In the first to third embodiments, as shown in FIG. 10, the transmission peak region 20 of the radiator 6 is set to one absorption wavelength λ of liver cancer cells. １ In contrast to this, in this embodiment, the transmission peak region 20 is made to overlap with a plurality of absorption wavelengths of liver cancer cells.

[0153] FIG. 22 is a diagram showing the transmission spectrum of the radiator 6 according to this embodiment.

[0154] As shown in FIG. 22, this transmission spectrum shows the absorption wavelengths λ １ , λ ２ , and has a transmission peak region 20 overlapping therewith.

[0155] When a bandpass filter is used as the radiator 6, by using the radiator 6 having such a transmission peak region 20 in the cancer cell killing device 1 of any of the first to third embodiments, each absorption wavelength λ １ , λ ２ Therefore, the radiator 6 radiates infrared light IR containing a plurality of absorption wavelengths λ １ , λ ２ Since liver cancer cells absorb all of the absorption wavelengths λ , apoptosis of liver cancer cells can be efficiently induced. Similarly, in the case of the radiator 6 utilizing Kirchhoff's law, the absorption peak region of the radiator 6 covers multiple absorption wavelengths λ １ , λ ２ By overlapping the two, apoptosis of liver cancer cells can be efficiently induced.

[0156] The apex Q of the transmission peak region 20 and each absorption wavelength λ １ , λ ２ The positional relationship with the absorption wavelength λ is not particularly limited. １ , λ ２ For example, in this example, the peak Q is located at the mean wavelength of two absorption wavelengths λ １ , λ ２ If there is a wavelength at vertex Q, then (λ １ +λ２ ) / 2. This allows the intensity of the infrared light IR to be adjusted to a plurality of absorption wavelengths λ １ , λ ２ It is possible to prevent bias towards either of the absorption wavelengths λ １ , λ ２ Similarly, in the case of the radiator 6 utilizing Kirchhoff's law, the apex of the absorption peak region of the radiator 6 is located at a plurality of absorption wavelengths λ １ , λ ２ By positioning the average wavelength of each absorption wavelength λ １ , λ ２ This allows the infrared light IR in the IR region to be uniformly absorbed by liver cancer cells.

[0157] (Fifth Embodiment) In the first to fourth embodiments, liver cancer cells were treated, but in this embodiment, any one of skin cancer, breast cancer, and uterine cancer is treated. The inventors calculated the thickness of each of the optical films 11 and 12 (see FIG. 3 ) required for the transmission peak region of the radiator 6 to overlap with the absorption wavelength of these cancer cells. The above-mentioned TFCalc was used for the calculation. The thickness of each of the optical films 11 and 12 obtained by the calculation will be described below.

[0158] Skin Cancer Figure 23 shows the infrared absorption spectra of normal cells and skin cancer cells. The horizontal axis of Figure 23 indicates the wave number of infrared light, and the vertical axis indicates the absorbance of infrared light. This also applies to Figures 27 and 31 described below. Note that Figure 23 is an excerpt of the main part from Paper 3 below.

[0159] (Paper 3) M. Kyriakidou and 4 others, "FT-IR spectroscopy study in early diagnosis of skin cancer", In Vivo, Vol. 31, pp. 1131-1137, 2017, International Institute of Anticancer Research

[0160] According to FIG. 23, the absorption wavelength specific to skin cancer cells, which is not found in normal cells, is 5734 nm.

[0161] 24 and 25 are diagrams showing an example of the thicknesses of the films 11x and 11y of the first optical film 11 when skin cancer is the target. As shown in Fig. 24 and 25, in this example, the total number of films 11x and 11y is 80.

[0162] 26 is a diagram showing an example of the thicknesses of the films 12x and 12y of the second optical film 12 when skin cancer is the target. As shown in FIG. 26, in this example, the total number of films 12x and 12y is 15.

[0163] By adopting the thicknesses shown in FIGS. 24 to 26, it is possible to obtain a radiator 6 having a transmission peak region at 5734 nm, which is an absorption wavelength specific to skin cancer cells.

[0164] Breast cancer: Figure 27 shows the infrared absorption spectra of normal cells and breast cancer cells. Figure 27 is an excerpt from the following paper 4.

[0165] (Paper 4) D. Simonova and 1 other author, "Application of Fourier transform infrared spectroscopy for tumor diagnosis", Biotechnology & Biotechnological Equipment, Vol. 27, pp. 4200-4207, 2013, Taylor & Francis

[0166] According to FIG. 27, the absorption wavelength specific to breast cancer cells, which is not found in normal cells, is 6050 nm.

[0167] 28 and 29 are diagrams showing an example of the thicknesses of the films 11x and 11y of the first optical film 11 when breast cancer is the target. As shown in Fig. 28 and 29, in this example, the total number of the films 11x and 11y is 81.

[0168] 30 is a diagram showing an example of the thicknesses of the films 12x and 12y of the second optical film 12 when breast cancer is the target. As shown in FIG. 30, in this example, the total number of layers of the films 12x and 12y is 15.

[0169] By adopting the thicknesses shown in FIGS. 28 to 30, it is possible to obtain a radiator 6 having a transmission peak region at 6050 nm, which is an absorption wavelength specific to breast cancer cells.

[0170] Uterine cancer: Figure 31 shows the infrared absorption spectra of normal cells, dysplastic cells, and uterine cancer cells. Note that Figure 31 is excerpted from the aforementioned paper 4.

[0171] According to FIG. 31, the absorption wavelength specific to uterine cancer cells, which is not found in normal cells, is 10310 nm.

[0172] 32 and 33 are diagrams showing an example of the thicknesses of the films 11x and 11y of the first optical film 11 when targeting uterine cancer. As shown in Fig. 32 and 33, in this example, the total number of films 11x and 11y is 90.

[0173] 34 is a diagram showing an example of the thicknesses of the films 12x and 12y of the second optical film 12 when targeting uterine cancer. As shown in Fig. 34, in this example, the total number of films 12x and 12y is 15.

[0174] By adopting the thicknesses shown in FIGS. 32 to 34, it is possible to obtain a radiator 6 having a transmission peak region at 10310 nm, which is an absorption wavelength specific to uterine cancer.

[0175] Although each embodiment has been described in detail above, the embodiments are not limited to the above. For example, while liver cancer, skin cancer, breast cancer, and uterine cancer have been described above as examples, the targets to be killed by the cancer cell killing device 1 according to each embodiment are not limited to these. For example, the targets to be killed by the cancer cell killing device 1 according to each embodiment may be any of various types of cancer cells, such as lung cancer, prostate cancer, pancreatic cancer, and colon cancer, by making the absorption wavelength of the cancer cell overlap the peak region of the radiator 6.

[0176] Furthermore, the method for selecting the absorption wavelength of cancer cells is not particularly limited. For example, the absorption wavelength of any cancer cell is λ, and the absorbance at the absorption wavelength λ of the cancer cell is A ｃ (λ), the absorbance of normal cells at the absorption wavelength λ is A ｎ (λ). In this case, A ｃ (λ) and Aｎ (λ) ratio A ｃ (λ) / A ｎ As an example, the ratio A ｃ (λ) / A ｎ A reference value R is set in advance for (λ), and the ratio value A ｃ (λ) / A ｎ A λ such that (λ) is greater than the reference value R may be selected as the absorption wavelength for cancer cells. The reference value R may be set to a value that can selectively induce apoptosis in cancer cells while reducing the impact of infrared irradiation on normal cells. As an example, the reference value R is preferably set to 1.5 or more, more preferably 3 or more. The reason for adopting 1.5 as the lower limit of the reference value R is that when cancer cells are heated to 42°C or higher, it is expected that normal cells will be kept at a temperature of approximately 40°C, and any temperature increase beyond this is thought to cause protein denaturation in normal cells. In addition, the reason for adopting 3 as the lower limit of the reference value R is that the absorption wavelength λ of liver cancer cells used in the first embodiment is 1.5, and the reason for adopting 3 is that the absorption wavelength λ of liver cancer cells used in the first embodiment is 1.5, and more preferably 3. １ (See Figure 1) ｃ (λ １ ) / A ｎ (λ １ ) was 3 or more, and in this case, apoptosis of liver cancer cells could be induced as described in the first embodiment, confirming the effectiveness of infrared light irradiation.

[0177] DESCRIPTION OF SYMBOLS 1...cancer cell killing device, 2...housing, 2a...open end, 3...heating element, 3a...reflector, 3b...tip, 3c...rear end, 3d...surface, 4...support rod, 5...cell, 6...radiator, 7...filter, 8...rod, 9...liver cancer cells, 10...substrate, 10a...first surface, 10b...second surface, 11...first optical film, 11x...Ge film, 11y...ZnS film, 12...second optical film, 12x...Ge film, 12y...ZnS film, 15...well plate, 15a...well, 15b...upper surface, 16...growth medium, 17...liver cancer cells, 20...transmission peak region, 22...transmission peak region, 23...absorption peak region, 30...radiation peak region, 31...radiation region, C...radiant light, IR...infrared light, P １ , P ２ …absorption peak, λ １ , λ ２...absorption wavelength, S...tissue.

Claims

1. A cancer cell killing device comprising: a heating element; and a radiator whose peak region, which is an absorption peak region or a transmission peak region, overlaps with the absorption wavelength of cancer cells, and which receives heat or radiant light generated by the heating element and radiates infrared light of the absorption wavelength.

2. The cancer cell killing device according to claim 1, wherein the radiator includes an optical film having the peak region.

3. The cancer cell killing device according to claim 2, wherein the optical film is a laminated film made up of a plurality of films made of different materials.

4. A cancer cell killing device according to any one of claims 1 to 3, further comprising a filter onto which the infrared light is incident, the filter having a transmission peak region whose wavelength overlaps with the peak region.

5. A cancer cell killing device according to any one of claims 1 to 4, wherein the radiator is a plate having a first surface that receives the heat or the radiant light and a second surface that faces the first surface and radiates the infrared light.

6. The cancer cell killing device according to claim 5, wherein the heat generating element is a heater provided at a distance from the first surface.

7. A cancer cell killing device according to any one of claims 1 to 6, wherein the radiator is in contact with the surface of the heat generating element.

8. The cancer cell killing device according to claim 7, wherein the heating element is a tungsten plate or a tantalum plate.

9. The cancer cell killing device according to claim 7, wherein the heating element is a granule, and the radiating element is a coating covering the surface of the granule.

10. A cancer cell killing device according to any one of claims 1 to 9, wherein the ratio of the infrared absorbance at the absorption wavelength of the cancer cells to the infrared absorbance at the absorption wavelength of normal cells is greater than a reference value.

11. A cancer cell killing device according to any one of claims 1 to 10, wherein the absorption wavelength is any one of 9548 nm or 9823 nm, which are absorption wavelengths of liver cancer cells, 5734 nm, which are absorption wavelengths of skin cancer cells, 6050 nm, which are absorption wavelengths of breast cancer cells, and 10310 nm, which are absorption wavelengths of uterine cancer cells.

12. A cancer cell killing device according to any one of claims 1 to 11, wherein the full width at half maximum of the peak region is 0.1 nm or more and 200 nm or less.

13. The cancer cell killing device according to claim 12, wherein the wavelength at the apex of the peak region is located within a wavelength range of ±50 nm of the absorption wavelength.

14. A cancer cell killing device according to any one of claims 1 to 13, wherein a plurality of absorption wavelengths exist, and each of the plurality of absorption wavelengths overlaps with the peak region.

15. The cancer cell killing device according to claim 14, wherein the wavelength at the apex of the peak region is the average wavelength of the plurality of absorption wavelengths.

16. A radiator for killing cancer cells, the peak region of which is an absorption peak region or a transmission peak region overlaps with the absorption wavelength of cancer cells, and which radiates infrared light of the absorption wavelength upon receiving heat or radiant light.

17. The radiator for killing cancer cells according to claim 16, further comprising an optical film having the peak region.

18. The radiator for killing cancer cells according to claim 17, wherein the optical film is a laminated film in which a plurality of films made of different materials are laminated.

19. A radiator for killing cancer cells according to any one of claims 16 to 18, further comprising a plate having a first surface that receives the heat or the radiant light and a second surface that radiates the infrared light opposite to the first surface.

20. A cancer cell killing device according to any one of claims 16 to 19, wherein the ratio of the infrared absorbance at the absorption wavelength of the cancer cells to the infrared absorbance at the absorption wavelength of normal cells is greater than a reference value.

21. A radiator for killing cancer cells according to any one of claims 16 to 20, wherein the absorption wavelength is any one of 9548 nm or 9823 nm, which are absorption wavelengths of liver cancer cells, 5734 nm, which are absorption wavelengths of skin cancer cells, 6050 nm, which are absorption wavelengths of breast cancer cells, and 10310 nm, which are absorption wavelengths of uterine cancer cells.

22. A radiator for killing cancer cells according to any one of claims 16 to 21, wherein the full width at half maximum of the peak region is 0.1 nm or more and 200 nm or less.

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