JP2005334129A - Target molecule manipulating device and target molecule manipulating method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a target molecule manipulating device and a target molecule manipulating method for effectively utilizing the electromagnetic waves of the ultrahigh frequency of a terahertz band and its vicinity, performing irradiation with the electromagnetic waves which resonate with the natural vibrations of biological molecules and manipulating a biological molecular structure. <P>SOLUTION: The target molecule manipulating device comprises: an electromagnetic wave irradiation means 7a for performing the irradiation with the electromagnetic waves of a frequency equal to the natural frequency of a biological target molecule in the range of 0.01THz-200THz and activating, transforming or destroying the target molecule; an electromagnetic wave generation means 13 for supplying the electromagnetic waves of the frequency to the electromagnetic wave irradiation means 7a; and a manipulated result measurement means 7b for measuring the electromagnetic waves transmitted through the target molecule or the electromagnetic waves reflected from the target molecule and detecting the change state of the target molecule by the irradiation with the electromagnetic waves. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to high-frequency electromagnetic wave application technology, and more particularly, to a target molecule manipulation device and a target molecule manipulation method for selectively manipulating molecules by irradiating molecules constituting biological cells with electromagnetic waves.

Cancer chemotherapy cannot be expected unless it is used to such an extent that side effects appear considerably. In fact, if there are strong side effects, it must be stopped and the therapeutic effect will not increase. For this reason, there are many examples of death due to side effects of anticancer drugs, not death from cancer.
In addition to cancer treatment, gene therapy has attracted attention for Down's syndrome, depression, asthma, rheumatism, myocardial infarction, and various chronic diseases. Current gene therapy does not directly normalize an abnormal gene, but incorporates a gene that induces an immune response into a detoxified virus and `` infects '' the cancer cell with the virus. It should be called "virus therapy". Viruses have the property of injecting their own genes into cells and causing gene expression. They act as gene carriers (vectors), and "immune inducers" are expressed on the surface of cancer cells. Cytokines such as interleukins (information transmission substances) and cell labeling substances such as HLA are used as immunity-inducing substances. For example, when a tumor suppressor gene called “p53” is carried into a vector and the gene is incorporated into a cancer cell, normal p53 protein is produced in the cancer cell that does not work normally, and the cancer cell becomes apoptotic (depending on the gene program). Expects the effect of self-destruction by causing cell suicide.

However, with current gene therapy, it is impossible to expect reproducibility in the effect of treatment because the location of the incorporated gene is unknown. For example, even if the p53 gene is incorporated, the gene is not incorporated where the p53 gene should be. Such uncertainties in gene integration lead to uncertainties in therapeutic effects. Also, gene integration can lead to unexpected abnormalities. In addition, whether it is adenovirus or liposome, the gene can be integrated into cancer cells and normal cells at the present time, so undesirable results such as side effects occur. Therefore, a vector that can be selectively incorporated into cancer cells is desired.
The p53 protein is considered to have a function of monitoring and controlling whether cell division is normally performed, and cancer cells are causing the tablets to break. When cancer was discovered, it was in a situation where the majority of cells had already repeated division, and there were many cells in which genes other than p53 were also damaged. All of these are difficult to treat with current methods of treatment.
By irradiating the object to be measured with an electromagnetic wave of 275 KHz to 1.01 MHz in the medium wave (MF) band and irradiating or applying an electromagnetic wave having the same frequency as the electromagnetic wave emitted by the microorganism, A method of selectively killing specific microorganisms (including viruses) has been proposed (see Patent Document 1). In the technique described in Patent Document 1, in particular, a single type or a plurality of types of specific metals by irradiating or applying an electromagnetic wave having the same frequency as the frequency of the electromagnetic wave emitted by the metal to a deposited metal element in a living body. Selective killing of one or more specific microorganisms in the living body, promotion of selective extracorporeal removal of one or more specific metal elements deposited in the living body, and further in vivo Is expected to kill multiple microorganisms.

However, electromagnetic waves at high frequencies such as a 3 MHz to 30 MHz short wave (HF) band, a 30 MHz to 300 MHz ultra high frequency (VHF) band, a 300 MHz to 3 GHz ultra-high frequency (UHF) band, and a microwave (SHF) band of 3 GHz or higher are also used. The influence on microorganisms and the inherent frequency of microorganisms are not known. In particular, there has been no effective electromagnetic wave generation means and measurement means, and biological molecular vibration data in the terahertz band called a dark zone of radio waves is almost none.
JP 2000-245813 A

  The present invention has been made to eliminate the above-described drawbacks of the prior art, and its object is to effectively utilize the terahertz band and the super-high frequency electromagnetic waves in the vicinity thereof, and to provide a biological molecular structure. It is an object to provide a target molecule manipulation apparatus and a target molecule manipulation method that can activate, transform, or destroy the target with good controllability.

  In order to achieve the above object, the first feature of the present invention is that (a) in the range of 0.01 THz to 200 THz, an electromagnetic wave having a frequency equal to the natural frequency of a biological target molecule is irradiated, (B) an electromagnetic wave generating means for supplying an electromagnetic wave of a frequency to the electromagnetic wave irradiation means, and (c) an electromagnetic wave transmitted through the target molecule or reflected from the target molecule. The gist of the present invention is a target molecule manipulation device provided with manipulation result measurement means for measuring and detecting a change state of a target molecule due to irradiation of electromagnetic waves.

  An example of the “biological target molecule” is a cell, and the cell membrane covering the cell, and the cytoplasm and nucleus in the cell membrane are other examples. The nucleus is separated from the cytoplasm around the nucleus by a nuclear membrane, which is also an example of a biological target molecule. In the cytoplasm of the cell, various organelles collectively called organelles such as endoplasmic reticulum, Golgi apparatus (body), lysosome, mitochondria, peroxime, etc. exist as examples of biological target molecules. Plant cells have the same basic structure, but contain chloroplasts and vacuoles, and the outside of the cell membrane is further covered by a cell wall, which is an example of a biological target molecule. For example, consider a peptidoglycan that forms a bacterial cell membrane. In this peptidoglycan, N-acetylglucosamine (GlcNAC) and N-acetylmuramic acid (MurAC) are alternately β-1,4 linked to form a long glycan chain. The amino acid is amide-bonded to the lactic acid residue of N-acetylmuramic acid to constitute a peptide consisting of four amino acids [L-Ala-D-Glu-DAP (Lys) -D-Ala]. Several to several tens of these basic units are connected to form a long chain structure. The glycan chains in the cell wall run parallel to each other and are cross-linked by the bond between peptide chains to create a macromolecule.

  The nucleus of the cell is packed with deoxyribonucleic acid (DNA), and the DNA is a super-large molecule with a molecular weight (number of molecules) exceeding tens of billions. It is stored as. This DNA is made of a series of structural units called “nucleotides”. Nucleotides are composed of two types of molecules, phosphate and deoxyribose, and one of four types of base molecules, adenine (A), thymine (T), guanine (G), and cytosine (C). In addition, the pentose of RNA (ribonucleic acid), which is another kind of nucleic acid, is ribose, and the base molecule also contains U (uracil) instead of thymine (T). FIG. 1 and FIG. 2 show the vibration characteristics of adenine (A), guanine (G), cytosine (C), uracil (U), and thymine (T) that were first clarified by the present inventors. As shown in FIG. 1A, adenine (A) has absorption peaks at 1.7 THz, 2.1 THz, 3.0 THz, and 4.2 THz. As shown in FIG. 1B, guanine (G) is 2.6 THz, 3.0 THz, 4.3 THz, 4.8 THz, 5.5 THz, and as shown in FIG. 1C, cytosine (C) is There are significant absorption peaks at 1.6 THz, 2.9 THz, 3.4 THz, 4.3 THz, and 5.3 THz, respectively. Further, as shown in FIG. 2 (d), thymine (T) is prominent at 2.3 THz and 3.0 THz, and as shown in FIG. 2 (e), U (uracil) is prominent at 3.33 THz and 3.8 THz, respectively. These absorption peaks show the unique frequency of each base molecule.

  Since DNA / gene is composed of a combination of four base molecules of adenine (A), thymine (T), guanine (G), and cytosine (C), DNA / gene also has its own vibration. . These frequencies can be measured with a terahertz-band electromagnetic wave measurement system, as in FIGS. In addition, it can be calculated from each vibration data of adenine (A), thymine (T), guanine (G), and cytosine (C) using molecular vibration theory (specifically, various types such as MOPAC, Abu Initio, etc.) The molecular vibrations can be calculated using the program.) In practice, three base molecules, three, combine to create an information unit called a “codon” that directs the production of one amino acid with one codon. Since three types of base molecules are combined, it represents 4 to the 3rd power = 64 types of amino acids, and production can be specified. In addition, a large number of codons are gathered to constitute genes and direct protein production.

  Actually, as shown in FIG. 3A, nucleotides are arranged in two rows, and four kinds of base molecules are connected in a ladder shape between them, and these are twisted in a spiral shape. A structure in which the ladder is twisted in a spiral shape is a “DNA double helix” structure. As shown in FIG. 3 (b), adenine and guanine necessarily face each other as thymine and cytosine as shown in FIG. 3 (c) to form a base pair. These base molecules, nucleotides containing them, codons consisting of a combination of nucleotides, DNA, RNA that is a combination of codons, nucleosomes in which DNA is regularly wrapped with a protein called histone, helical nucleosomes consisting of nucleosomes, helical nucleosomes An example of a biological target molecule is a chromatin composed of, a chromosome in which the chromatin is aggregated, a protein, and the like.

  Biological macromolecules such as cell walls, cell membranes and DNA have natural vibrations different from various vibration modes depending on the molecular chain structure. For example, the bending vibration of 3 molecules and the stretching vibration between 5 molecules are different natural vibrations. In addition, there is a ring bending vibration that dances around a specific bond while rotating. As described above, various natural frequencies exist in the terahertz band depending on the vibration mode of the biological target molecule. Furthermore, since it differs depending on whether the vibration is a longitudinal wave or a transverse wave, and whether the vibration is a fundamental vibration or a harmonic vibration, there are many natural vibrations in the terahertz band and the high-frequency band near the terahertz band.

  When DNA doubles, the original DNA and the copy of the DNA are not distributed to the daughter cells, but the DNA molecules made up of the original DNA half and the copy DNA half are in the daughter cells. Distributed. However, the end portion of the filamentous DNA molecule cannot be replicated by any means, and the portion that could not be replicated becomes shorter. The terminal DNA is called a telomere, has a special base sequence, and has a unique frequency. The telomeres at the ends of the linear DNA are shortened at every cell division, so that the cells cannot divide and die after a certain number of times. However, germ cells can grow indefinitely because there is an enzyme called telomerase that makes and compensates for telomeres. Telomerase is also found in cells that divide indefinitely, such as cancer cells. Telomeres are generally shorter in mitotic cancers, but can still survive because telomerase is expressed and compensates for its consumption. A population of cancer cells is an aggregate of cancer cells with an infinite number of different abnormal chromosomes and phenotypes. This atypia is a characteristic of cancer cells, and it is thought that the mutual connection and translocation of chromosomes frequently occur due to the extreme shortening of telomeres that stabilize the chromosome structure. If telomerase as a biological target molecule is destroyed by irradiation with electromagnetic waves, the telomeres disappear and cancer cells cannot survive, so that the expression of cancer stops.

  In addition, cancer cells secrete proteases such as plasminogen activator and collagenase, which are considered to be advantageous for cancer cell invasion and metastasis formation. For this reason, if these proteases are used as biological target molecules and an electromagnetic wave having an inherent frequency is irradiated to destroy or transform the protease, invasion or metastasis of cancer cells can be suppressed.

  When a cancer cell is irradiated with a medium wave (MF) band electromagnetic wave as described in Patent Document 1, macromolecules such as cell membranes are destroyed, and the cancer cell falls into cell necrosis (necrosis). Necrosis is characterized by the fact that leukocytes accumulate around the cell contents due to cell disintegration due to cell disruption, resulting in an inflammatory reaction, which further causes cancer epidemic. In contrast, when a terahertz band electromagnetic wave is irradiated to a target molecule (biological target molecule) of a cancer cell, the cancer cell is induced by apoptosis. In the case of apoptosis, since fragmented cells are phagocytosed by macrophages and processed, it is effective because it is not accompanied by an inflammatory reaction and hardly invades the living body. Apoptosis is an originally morphologically defined concept, a mode of cell death in contrast to necrosis. Apoptotic cells contract and the nucleus concentrates and fragments. Apoptotic bodies are formed in which fragmented nuclei are enveloped by cell membranes, which are processed by phagocytes. This process is controlled by a series of genes and is actively performed by consuming energy. Unlike necrosis, it is an important mechanism for maintaining homeostasis of the cellular environment in the living body because it does not cause inflammation in principle.

  In principle, the target molecule manipulation device according to the first feature of the present invention can use electromagnetic waves from a low frequency of about several tens of kHz to a high frequency in the terahertz band. However, since the natural vibration of the condensed dyed body, the natural vibration of the flexural vibration, and the like depend on the size of the microorganism or cell as an individual, the frequency adjustment is complicated. On the other hand, the natural vibration due to the molecular vibration that constitutes the cell of the biological target molecule can be made almost constant if the boundary condition is constant if the type of biological target molecule is determined. Adjustment is easy. For this reason, it is preferable to use electromagnetic waves in a terahertz band or a high frequency band near the terahertz band in practice.

  According to the first feature of the present invention, an electromagnetic wave having a frequency equal to the natural frequency of the biological target molecule is emitted from the electromagnetic wave irradiation terminal at the tip of the capillary tube. An electromagnetic wave with a frequency equal to the natural frequency of the biological target molecule selectively excites the target biological target molecule so as to resonate and vibrate cells around the biological target molecule. Only biological target molecules can be killed without destroying etc. Therefore, it is possible to effectively treat diseases such as infectious diseases caused by biological target molecules. As described above, since there are generally multiple natural frequencies of biological target molecules, electromagnetic waves having different frequencies equal to the multiple natural frequencies can be emitted from the electromagnetic wave irradiation terminal or cause resonance vibrations at the same time. good.

  Furthermore, it absorbs the energy of electromagnetic waves and activates local reactions by utilizing the local and selective increase in the temperature of biological target molecules, thereby reducing the dose of anticancer drugs and the like. It is possible to treat cancer and the like without causing side effects on normal cells. When the natural frequency of the biological target molecule changes due to the temperature rise, the frequency of the electromagnetic wave may be changed following the change to maintain the resonance vibration state.

    The second feature of the present invention is that (a) a step of cleaving DNA at a desired cleavage site, and (b) an end codon present at the end of the cleavage site or an end base molecule constituting this end codon A target that changes the DNA base sequence by irradiating electromagnetic waves with a frequency equal to the natural frequency of, selectively activating end codons or end base molecules, and connecting other codons to the cut site The gist is that it is a molecular manipulation method.

  According to the second feature of the present invention, it becomes possible to incorporate other codons freely and with high reproducibility into DNA cleavage sites.

  As described above, according to the present invention, a target molecule manipulation device and a target molecule that can effectively use, transform, or destroy a biological molecular structure with good controllability by effectively using a terahertz band and an ultrahigh-frequency electromagnetic wave in the vicinity thereof. An operation method can be provided.

  Embodiments of the present invention will be described below with reference to the drawings. In the following description of the drawings, the same or similar parts are denoted by the same or similar reference numerals. However, it should be noted that the drawings are schematic and the shapes, dimensions, and the like are different from the actual ones. Also, the following first to fourth embodiments exemplify apparatuses and methods for embodying the technical idea of the present invention, and the technical idea of the present invention is the component parts. The material, shape, structure, arrangement, etc. are not specified below. The technical idea of the present invention can be variously modified within the scope of the claims.

(First embodiment)
As shown in FIGS. 4 and 5, the target molecule manipulation device according to the first embodiment of the present invention has a frequency equal to the natural frequency of the biological target molecule in the range of 0.01 THz to 200 THz. An electromagnetic wave irradiation means 7a that activates, transforms or destroys the target molecule by irradiating the electromagnetic wave Φ, and an electromagnetic wave Φ transmitted through the target molecule or an electromagnetic wave Φ reflected from the target molecule is measured, and the target molecule by irradiation with the electromagnetic wave Φ is measured. This is a medical device provided with an operation result measuring means 7b for detecting the change state of the sensor, a treatment condition control device 1a for controlling the electromagnetic wave irradiation means 7a and the operation result measuring means 7b. 5 and 6, the electromagnetic wave irradiation means 7a is shown as an irradiation thin tube (irradiation probe) 7a, and the operation result measurement means 7b is shown as a monitoring thin tube (monitoring probe) 7b.

  The outer diameters of the illuminating tubule 7a and the monitoring tubule 7b are preferably set to about 0.1 mm to 20 mm in accordance with the site to be treated so as not to give burden, pain or discomfort to the treated side. For example, in the case of an endoscope inserted into a digestive organ such as the large intestine and the small intestine, the outer diameter may be about 10 mm to 20 mm, and in the case of an endoscope inserted from the mouth like a stomach camera, about 1 mm to 10 mm. Is preferred. 4 and 5, the irradiation tubule 7a and the monitoring tubule 7b are described as an irradiation laparoscopic probe 7a and a monitoring laparoscopic probe 7b used for laparoscopic cholecystectomy, etc. A structure similar to a needle-like instrument (needle) used for surgery or a catheter for insertion into a blood vessel or body cavity may be used.

  As shown in FIG. 5, the laparoscopic probe for irradiation 7a includes a high-frequency transmission line 70a for transmitting electromagnetic waves, a light guide 72 for irradiating light to the living body, and a treatment target object in a tube 77 inserted into the living body. It has a temperature detection means (temperature detection terminal) 73 for detecting temperature and a CCD camera 71 for acquiring video information inside the living body. At the tip of the high frequency transmission line 70a, there is provided an electromagnetic wave irradiation terminal 74a that irradiates the treatment target with the electromagnetic wave propagated through the high frequency transmission line 70a. The CCD camera 71, the light guide 72, the temperature detection terminal 73, and the high-frequency transmission line 70a are respectively arranged in the tube 77 along the longitudinal direction. As illustrated in FIG. The tip of the probe 7a is exposed.

  In FIG. 6, the CCD camera 71, the light guide 72, the temperature detection terminal 73, and the electromagnetic wave irradiation terminal 74a are arranged in a line, but need not be arranged in a line, and other arrangements can be adopted. For example, when a coaxial cable is used as the high-frequency transmission line 70, a CCD camera 71, a light guide 72, and a temperature detection terminal 73 are arranged so as to surround the signal line of the coaxial cable inside the insulating layer of the coaxial cable. A structure in which the ground side wiring of the coaxial cable is provided on the outer side may be used.

  The other ends of the CCD camera 71, light guide 72, and temperature detection terminal 73 are connected to the laparoscope control device 18a shown in FIG. The CCD camera 71 preferably has an objective lens at one end of the irradiation laparoscopic probe 7a on the side to be inserted into the treatment target. The light guide 72 uses a visible light optical fiber. The light guide 72 may transmit not only the illumination light but also the image. That is, if the image obtained through the light guide 72 is separated by a beam splitter or the like, and the image information is acquired by the CCD camera after the separation, the CCD camera 71 of FIG. 5 is unnecessary. For use as a transmission line for video information, a so-called “convergent optical transmission line (graded index) having a parabolic distribution in which the refractive index distribution of the light guide 72 is high on the central axis and low on the outer peripheral side. Fiber) ”. The temperature detection terminal 73 may be a T-type (Cu—Co) thermocouple or the like, and may measure the temperature optically via an infrared optical fiber. When measuring the temperature optically, the light guide 72 can also serve as the temperature detection terminal 73 if the material of the light guide 72 is selected as a material that transmits visible light and infrared light.

  As the electromagnetic wave irradiation terminal 74a provided at the distal end portion of the irradiation laparoscopic probe 7a, a parabolic antenna, a horn antenna, a loop antenna, or the like can be used. The electromagnetic wave irradiation terminal 74a is utilized by a distal end portion of a high-frequency transmission line 70 such as a waveguide-type flexible hollow light guide that can transmit terahertz band electromagnetic waves, a coaxial cable, a microstrip line, a coplanar waveguide, What is necessary is just to process in a parabola shape, a horn shape, and a loop shape.

  As is well known, in the far-field region that is sufficiently far away from the wavelength λ of electromagnetic waves, the maximum power is radiated in the direction of the loop surface and the power in the direction perpendicular to the loop surface is minimum. The direction of the loop surface may be selected in consideration of the above. The size of the loop antenna is preferably close to the resonance wavelength λ of the electromagnetic wave in order to increase the radiation efficiency. By making the frequency higher than the millimeter wave (EHF) band of 30 GHz to 300 GHz, the loop diameter can be easily reduced to 1 mm or less, and the laparoscopic probe 7a for irradiation can be downsized, in particular, the outer shape of the laparoscopic probe 7a for irradiation can be reduced. Can be realized. If the outer shape of the irradiation laparoscopic probe 7a is 0.3 mm or less, preferably 0.25 mm or less, the burden on the patient can be reduced and the laparoscopic probe for irradiation can be inserted into the organ (currently the smallest in the world) The outer diameter of the injection needle is 0.15 mm). If the refractive index of the insulator surrounding the loop antenna is 2, the wavelength of the electromagnetic wave of 30 GHz is 5 mm, and the diameter of the loop antenna is 1.6 mm. However, the shape of the loop antenna is not particularly limited, and loop antennas having various shapes such as a circle, an ellipse, a flat circle, a rectangle, a triangle (delta) shape, a pentagon or more polygon combined with a coaxial line can be used. (The polygon need not be a regular polygon.) When the loop antenna is downsized, the tip of the signal line that constitutes the high-frequency transmission line is patterned into various shapes such as a circle, ellipse, flat circle, rectangle, triangle, pentagon or more by photolithography technology. Just do it. Since not only the outer diameter of the loop antenna but also the dimensions of the high-frequency transmission line may be affected by the wavelength of the propagating electromagnetic wave, using a high-frequency electromagnetic wave in the millimeter wave (EHF) band or more, the laparoscope for irradiation The external shape of the probe 7a can be reduced, and the burden on the patient can be reduced.

  If the electromagnetic wave has a higher frequency than the submillimeter wave band, the diameter of the flexible waveguide (hollow light guide) as the high-frequency transmission line 70 can be 1 mm or less. The electromagnetic wave irradiation terminal 74 a may be a far-infrared lens provided at the tip of a far-infrared optical fiber as the high-frequency transmission line 70. As the far-infrared optical fiber, materials such as KRS-5 (TlBrI), TlBr, AgCl, AgBr, germanium oxide glass, and fluorine glass can be used. A semiconductor material such as high-purity silicon that does not contain shallow impurities can also be used as a material for the far-infrared optical fiber. When a far-infrared optical fiber is used as the high-frequency transmission line 70, a far-infrared lens or the like is provided at the other end of the high-frequency transmission line 70a facing the electromagnetic wave irradiation terminal 74a. After being introduced and propagating through the high-frequency transmission line 70, it is emitted from the electromagnetic wave irradiation terminal 74a.

  If the material of the light guide 72 is selected as a material such as diamond that transmits visible light to far infrared light or a hollow light guide (waveguide), the light guide 72 and the high-frequency transmission line 70 may be used together. In this case, since the temperature can also be measured optically via the light guide 72, the light guide 72 can serve as both the high-frequency transmission line 70 and the temperature detection terminal 72. A variable stub 87 for impedance adjustment connected to the high frequency transmission line 70 is provided in the vicinity of the electromagnetic wave irradiation terminal 74a. The variable stub 87 is connected to the high-frequency transmission line 70 via the microactuator 88 and is driven by the microactuator 88. Although the detailed structure is not shown, the variable stub 87 may be selected according to the structure of a high-frequency transmission line such as a waveguide, a coaxial cable, a microstrip line, or a coplanar waveguide. As described above, if the light guide 72 is not used only for illumination light but is used as a transmission line for video information, the CCD camera 71 is unnecessary. Therefore, if the light guide 72 is a wide band material that transmits all visible light to far infrared light, the CCD camera 71, the high frequency transmission line 70, and the temperature detection terminal 73 in FIG. 5 can be omitted. With such a structure, an irradiation laparoscopic probe having an outer diameter of 0.1 mm or less can be realized.

  As shown in FIGS. 4 and 7, the monitor laparoscopic probe 7b has an electromagnetic wave detection terminal 74b disposed at a position facing the tip of the irradiation laparoscopic probe 7a. That is, the object to be treated is sandwiched between the electromagnetic wave irradiation terminal 74a at the distal end of the irradiation laparoscopic probe 7a and the electromagnetic wave detection terminal 74b at the distal end of the monitoring laparoscopic probe 7b, and the electromagnetic wave that has passed through the treated object is monitored. It is detected by the tip of 7b.

  It has been stated that the outer diameter of the monitor capillary (monitor laparoscopic probe) 7b should be about 0.1 mm to 20 mm. However, considering the current state of treatment, the monitor laparoscope probe 7b is generally used. The outer diameter is thinner than the laparoscopic probe for irradiation 7a and is preferably about 0.1 mm to 10 mm. In particular, as a usage mode of the monitor laparoscopic probe 7b, the tip is often inserted to the inside of the organ to be treated. In such a case, the outer diameter is 0.8 mm or less, Is preferably 0.5 mm or less. For example, if a simple structure such as a structure in which a terahertz band electromagnetic wave detector such as a silicon bolometer is provided as the electromagnetic wave detection terminal 74b at the tip, the outer diameter of the monitor laparoscopic probe 7b is 0.2 to 0.1 mm. It is possible to: In order to insert the tip to the inside of the organ to be treated, the tip of the monitor laparoscopic probe 7b may have an acute taper shape like the tip of the injection needle. However, when both the irradiation laparoscopic probe 7a and the monitoring laparoscopic probe 7b are inserted into the organ, the burden on the patient is smaller when both the probes 7a and 7b are thinner than the outer diameter of the injection needle. .

  The monitor laparoscopic probe 7b may be configured to incorporate a high-frequency transmission line 70b composed of a horn antenna and a waveguide as an electromagnetic wave detection terminal 74b as shown in FIG. Further, the monitor laparoscopic probe 7b may be configured by incorporating a high-frequency transmission line such as a microstrip line, a thin film strip line, a coplanar waveguide, or a coaxial line other than the waveguide 70b. For example, as shown in FIG. 8, a loop antenna as the electromagnetic wave detection terminal 74b may be formed on the end surface by the photolithography technique at the distal end portion of the monitor laparoscopic probe 7b. Furthermore, a terahertz band electromagnetic wave detector such as a Schottky diode or a bolometer may be provided inside the monitor laparoscopic probe 7b.

  As described above, in the loop antenna, the maximum power is radiated in the direction of the loop surface, and the power in the direction perpendicular to the loop surface is minimum. Therefore, if the directivity of the antenna is taken into consideration, the loop surface is a laparoscopic probe for monitoring. 7 and 7b, the axial direction of the irradiation laparoscopic probe 7a and the axial direction of the monitor laparoscopic probe 7b are orthogonal to each other as shown in FIGS. The electromagnetic wave transmitted through the treatment object 2 can be detected by the loop antenna at the tip of the monitor laparoscopic probe 7b. The dimension (loop length) of the loop antenna as the electromagnetic wave detection terminal 74b is also preferably a dimension that has a resonance wavelength λ in order to increase the detection sensitivity. A minute loop antenna having a loop length of λ / 7 or less may be used. By using high-frequency electromagnetic waves of the millimeter wave (EHF) band or higher, particularly terahertz electromagnetic waves, the external shape of the monitor laparoscopic probe 7b can be reduced, and the burden on the patient can be reduced, and insertion into the organ can be achieved.

  A terahertz band image sensor such as a bolometer array is provided as an electromagnetic wave detection terminal 74b at the distal end of the monitor laparoscopic probe 7b, and a two-dimensional transmission image of the terahertz band electromagnetic wave transmitted through the treatment target (organ) is captured. You may do it.

  As shown in FIG. 4, the treatment condition control apparatus 1a includes a laparoscope control apparatus 18a, electromagnetic wave generation means 13, and transmitted electromagnetic wave processing means 14, molecular vibration data storage device 15, input device 11, display device 16, and output device 17. Is provided.

  As shown in FIG. 4, the laparoscope control device 18a is connected to the CCD camera 71 and the temperature detection terminal 73 inside the irradiation laparoscope probe 7a, and is connected to the output side of the signal processing unit 80. And a light source 82 connected to the light guide 72 inside the irradiation laparoscopic probe 7a. The signal processing unit 80 further includes a video processing unit 81 and a temperature signal processing unit 83. As the video processing unit 81 and the temperature signal processing unit 83, a video analysis processing device and a temperature measurement device can be used. As the light source 82, a visible light semiconductor laser, a visible light emitting diode, a discharge tube, a fluorescent lamp, or the like is used. A visible light semiconductor laser or a visible light emitting diode may be provided at the tip of the probe. Visible semiconductor lasers and visible light emitting diodes may be white light that is a mixture of R (red), G (green), and B (blue). Also good.

  The electromagnetic wave generating means 13 is a means for generating an electromagnetic wave having a frequency equal to the natural frequency of the target treatment target and supplying the electromagnetic wave to the irradiation laparoscopic probe 7a. For example, as shown in FIG. 4, the electromagnetic wave generating means 13 includes a relatively wideband electromagnetic wave generator 35 that generates an electromagnetic wave Φ having a frequency equal to the natural frequency of the treatment target, and changes in the natural vibration of the treatment target. It is comprised with the frequency adjustment part (frequency adjustment apparatus) 34 which changes the frequency of the electromagnetic waves which follow and irradiate to a to-be-treated object. In this case, a nonlinear optical element or the like is used for the frequency adjusting device 34.

As the electromagnetic wave generator 35, for example, a terahertz band electromagnetic wave generator that extracts a frequency difference between two pump lights as shown in FIGS. 10 and 11 may be used. In FIG. 10, light having a wavelength of 1.064 μm from an Nd: YAG laser 49 is used as the first pump light 51, and an optical parametric oscillator (OPO) pumped by the Nd: YAG laser 49 is used as the second pump light 52. 50 variable wavelengths of 1.03 to 1.06 μm are used. After the first pump light 51 is emitted from the Nd: YAG laser 49, the reflecting mirror M ₁ , the reflecting mirror M ₂ , the 3 mmΦ pinhole H ₂ , the reflecting mirror M ₃ , the reflecting mirror M ₄ , and the λ / 2 wavelength plate P _2. Then, the light enters the pump light control unit 54 via the polarization beam splitter (Grand prism) GP2, the reflecting mirror M ₅ , and the reflecting mirror M ₆ . The second pump light 52 is emitted from the optical parametric transmitter 50 and then pumped through a λ / 2 wave plate P ₁ , a 3 mmΦ pinhole H ₁ , a polarizing beam splitter (Grand prism) GP 1, and a reflecting mirror M _7. The light enters the control unit 54. The pump light control unit 54 emits the first pump light 51 and the second pump light 52 as combined light 53a and 53b, respectively. For the pump light control unit 54, for example, a polarization beam splitter (gran prism) is used. As shown in FIG. 11, the combined lights 53a and 53b emitted from the pump light controller 54 are perpendicularly incident on the incident end face 56 of the electromagnetic wave generator 55, and the electromagnetic wave generator 55 includes the first pump light 51 and the second pump light. An electromagnetic wave (a terahertz band electromagnetic wave) Φ having a frequency equal to the frequency difference from the light 52 is emitted from the emission end face 57.

As shown in FIG. 11, the electromagnetic wave generation unit 55 is positioned between the incident end face 56, the outgoing end face 57 facing the incoming end face 56, and a single mirror index located between the incoming end face 56 and the outgoing end face 57. And an optical waveguide 58 along the crystal orientation of the crystal. The entrance end face 56 and the exit end face 57 are coated with, for example, a SiO ₂ —TiO ₂ multilayer deposited film. The optical waveguide 58 is, for example, a ridge type optical waveguide composed of a GaP core layer having a ridge structure and a clad layer having an Al _x Ga _1- XP layer formed around the GaP core layer. When the combined lights 53a and 53b are incident on the GaP core layer of the incident end face 56, the difference frequency light coupled with the TO phonon is excited and the electromagnetic wave Φ having a frequency equal to the difference between the first frequency and the second frequency from the emission end face 57. Will occur.

  In the electromagnetic wave generator 35 shown in FIGS. 10 and 11, by changing the angle of the pump light control unit 54, the directions of the incident vectors of the first pump light 51 and the second pump light 52 are changed. The frequency of the difference between the first frequency and the second frequency emitted from the emission end face 57 is made variable. More broadly, the frequency of the second pump light 52 is made variable by an optical parametric transmitter (OPO) 50 to obtain a wide band. That is, the pump light control unit 54 and the optical parametric transmitter (OPO) 50 constitute a frequency adjusting unit (frequency adjusting device) 34 of the electromagnetic wave generating means 13 shown in FIG. As the optical parametric transmitter (OPO) 50, various parametric lasers can be used. For example, a single variable frequency terahertz wave having an arbitrary frequency can be generated in a terahertz frequency range from 0.2 THz to 7 THz by the parametric effect of a semiconductor GaP crystal. On the other hand, when the parametric effect of the dielectric LiNbOs is used, a single variable number terahertz wave can be generated in a frequency region within the range of 0.5 THz to 3 THz. Similarly, a terahertz variable frequency electromagnetic wave can be generated by using a Raman laser using a semiconductor or a dielectric instead of the optical parametric transmitter (OPO) 50.

  The other end of the high-frequency transmission line 70a connected to the electromagnetic wave irradiation terminal 74a is not necessarily connected to the laparoscope control device 18a built in the treatment condition control device 1a of FIG. For example, as shown in FIG. 12, an electromagnetic wave input terminal 76a is provided at the other end of the high frequency transmission line 70a so that the output of the electromagnetic wave generating means 13 of FIG.

  FIG. 12 shows a case where a loop antenna is provided as the electromagnetic wave input terminal 76a. For example, when the angle of the pump light control unit 54 is changed as the frequency adjustment unit (frequency adjustment device) 34, the direction of the terahertz electromagnetic wave emitted from the electromagnetic wave generation unit 55 changes. The optical system is configured such that terahertz electromagnetic waves are emitted in a fixed direction using the axis and parabolic mirrors 59a and 59b. The loop surface of the loop antenna serving as the electromagnetic wave input terminal 76a is positioned along this fixed direction so that terahertz electromagnetic waves can be incident from the other end of the high-frequency transmission line 70a. However, the electromagnetic wave input terminal 76a need not be limited to the loop antenna, and may be other means such as a parabolic antenna or a horn antenna. And the frequency and intensity | strength of the electromagnetic wave which propagates the high frequency transmission line 70a and is radiate | emitted with respect to the to-be-treated object 2 from the electromagnetic wave irradiation terminal 74a are controlled by the laparoscope control apparatus 18a shown in FIG.

In addition, materials such as zinc telluride (ZnTe) and lithium niobate (LiNbO ₃ ) may be used for the optical waveguide 58 shown in FIG. Further, the first pump light 51 and the second pump light 52 are not limited to those illustrated in FIG. 10, but are single mode laser diodes, distributed feedback (DFB) type semiconductor lasers, and variable wavelength semiconductor lasers having a resonator and grading. It may be oscillated from a light source using

Other examples of the electromagnetic wave generator 35 shown in FIG. 4 include millimeter waves such as a magnetron, a traveling wave tube, an electron tube such as a klystron and a calcinotron, a gas laser such as an H ₂ O laser, an O ₂ O laser, an HCN laser, and a DCN laser. Various electromagnetic wave generators in the far-infrared region from the waveband may be used. Furthermore, a terahertz band solid-state oscillation device having functions superior in terms of small size, light weight, low voltage, low power consumption, and the like as compared with an electron tube, a gas laser, and the like can be used. However, in a resonator using a solid oscillation element, the output decreases as the frequency increases, noise characteristics increase, and the frequency becomes unstable. The conditions of the resonator for a solid oscillator that solves the problem of increased noise characteristics and frequency instability are (1) a high Q value, (2) a structure capable of synchronous oscillation and power synthesis. 3) The size of the resonator is larger than the wavelength. As such a terahertz-band electromagnetic wave generator 35, an oscillator using a quasi-optical resonator can be used. For example, an oscillator using a quasi-optical Fabry-Perot resonator using a concave mirror and a diffraction grating may be used to perform synchronous oscillation and power synthesis using a terahertz band transmitting element such as a Gunn diode, tannet, or ideal SIT. If a wavelength variable electromagnetic wave generator 35 such as a spin flip Raman laser is used as the electromagnetic wave generator 13, the frequency adjusting device 34 can be omitted. Furthermore, each electromagnetic wave generator 35 may be prepared corresponding to a plurality of frequency bands, and finally the frequency region band covered by the electromagnetic wave generator 13 may be expanded. In addition, as described above, since there are a plurality of natural vibrations of the treatment target for each specific treatment target, a plurality of electromagnetic wave generators 35 are prepared according to each natural vibration, and a plurality of frequencies are simultaneously generated. It may be possible to irradiate electromagnetic waves. A plurality of frequency adjusting devices 34 are prepared corresponding to the plurality of electromagnetic wave generating devices 35. The transmitted electromagnetic wave processing means 14 shown in FIG. 4 processes the output signal from the terahertz band electromagnetic wave detector provided at the tip of the monitor laparoscopic probe 7b, and analyzes the absorption spectrum of the electromagnetic wave Φ transmitted through the treatment target. Circuit. For example, a low noise amplifier 41 that amplifies the output of the terahertz band electromagnetic wave detector, an A / D converter 42 that converts the output of the low noise amplifier 41 into a digital signal, and an absorption spectrum analysis that analyzes the absorption spectrum using the digital signal. Part 43. When only the receiving antenna is provided at the tip of the monitor laparoscopic probe 7b and the terahertz band electromagnetic wave detector is not provided, the terahertz band electromagnetic wave detector is provided at the first stage of the transmitted electromagnetic wave processing means 14, and the terahertz band electromagnetic wave detector is provided. The output may be amplified by the low noise amplifier 41.

The molecular vibration data storage device 15 of the treatment condition control apparatus 1a shown in FIG. 4 includes five base molecules of adenine (A), thymine (T), guanine (G), cytosine (C) and U (uracil). Codons comprising nucleotides, codons consisting of a combination of nucleotides, DNA, RNA, nucleosomes in which DNA is regularly wound with a protein called histone, helical nucleosomes consisting of nucleosomes, chromatin consisting of helical nucleosomes, staining Data on molecular vibrations measured experimentally in advance, such as chromosomes and proteins with aggregated quality, are stored. Furthermore, telomerase that causes infinite division of cancer cells, molecular vibration data of proteases such as plasminogen activator and collagenase, which are thought to favor the formation of cancer cell invasion and metastasis, are stored. ing. Furthermore, various molecular vibration data unique to the treatment target obtained experimentally, such as reduced glucose molecular vibration data unique to cancer cells, are also stored. The molecular vibration data storage device 15 stores not only static data but also dynamic data that changes in time series. For example, in the case of cancer treatment, before the treatment, prepare a plurality of cells of the same type with different progression states in advance, and prepare a sample in which each is cut into a thickness of about 1 mm. It is only necessary to measure the absorption characteristic of the electromagnetic wave that passes through and to measure the natural vibration frequency of the cancer cell. T ₃ , T ₂ , and T _{1 in} FIG. 9 show changes in absorption peaks of the cancer cells of the gastric cancer that were experimentally measured in advance as the cancer progressed. Gastric cancer cells contain a large amount of reduced glucose that produces an absorption peak A at 1.37 THz at room temperature, and normal tissue cells contain a lot of normal glucose that produces a peak B at 1.5 THz at room temperature. For this reason, FIG. 9 shows that the intensity of peak A increases sequentially from T ₃ → T ₂ → T ₁ and the peak B decreases sequentially as the cancer progresses (the data in FIG. 9 shows the progression of cancer progression). In addition to time-series data, data on changes in the frequency of molecular vibrations associated with changes in the temperature of the cells to be treated are also tested in advance. And is stored in the molecular vibration data storage device 15 as a database. Although the cancer cells have been exemplarily described, the molecular vibration data storage device 15 may store data of base molecules, nucleotides, codons, and DNA molecular vibrations of microorganisms such as microprotobacterium. Although there are 20 types of amino acids constituting the protein of the cell, all of them have vibration absorption peaks unique to the terahertz band, and therefore these molecular vibration data may be stored. Furthermore, not only the individual vibration spectra of these elements but also the overall vibrations of the bacteria and cancer cells themselves generate a unique spectrum as a single macromolecule, and this is used as molecular vibration data as the molecular vibration data storage device 15. You may memorize.

  The frequency of the natural vibration is determined by measuring the standing wave ratio (VSWR) of the electromagnetic wave irradiated to the treatment target with a reflectometer or the like in addition to the measurement of the transmission characteristic of the electromagnetic wave as shown in FIG. It may be stored in the storage device 15. Alternatively, the treatment target may be irradiated with a pulse wave, determined by frequency response measurement of the transmitted wave or reflected wave, and stored in the molecular vibration data storage device 15. Further, when the object to be treated is accompanied by an action such as a microorganism, the microorganism or the like is irradiated with an electromagnetic wave Φ, and the action or state change of the microorganism or the like is observed in-situ with a microscope or the like via the light guide 72 (in situ). The natural frequency may be specified by monitoring) and stored in the molecular vibration data storage device 15. According to the knowledge of the present inventor, most of these data exist in the range of 0.01 THz to 200 THz.

The CPU 12 of the treatment condition control device 1a shown in FIG. 4 includes a molecular vibration analysis unit 21, a treatment frequency determination unit 22, and a treatment effect determination unit 23. For example, in the case of gene therapy, the molecular vibration analysis unit 21 reads molecular vibration data such as base molecules, nucleotides, and codons from the molecular vibration data storage device 15 and uses this to cut DNA necessary for gene recombination. This is a software program that calculates the molecular vibration of a codon at a location using molecular vibration theory. Various molecular vibration data calculated by the molecular vibration analysis unit 21 are also stored in the molecular vibration data storage device 15 as a database. The molecular vibration analysis unit 21 also calculates a change in the frequency of molecular vibration accompanying a change in the temperature of the cell to be treated, and stores this in the molecular vibration data storage device 15 as a database. For example, if the data of the change in the frequency of molecular vibration accompanying the temperature change of the cell is experimentally obtained at the jumping point, it is obtained as continuous data interpolated and used as a database for molecular vibration. The data is stored in the data storage device 15.
The treatment frequency determination unit 22 is a molecular vibration data calculated by the molecular vibration analysis unit 21, or a telomerase, a protease such as plasminogen activator or collagenase read out from the molecular vibration data storage device 15, and a reduction specific to cancer cells. This is a software program that determines a frequency used as a treatment condition from molecular vibration data of various molecules such as glucose, and controls the frequency adjusting device 34 of the electromagnetic wave generating means 13 based on the determination result.

The therapeutic effect determination unit 23 is a software program that obtains an absorption spectrum of the electromagnetic wave Φ transmitted through the treatment target from the transmitted electromagnetic wave processing means 14 and confirms the therapeutic effect. For example, in the case of the treatment of gastric cancer shown in FIG. 9, the intensity of the peak A gradually decreases with the lapse of time T ₁ → T ₂ → T ₃ along with the irradiation of the electromagnetic wave emitted from the irradiation laparoscopic probe 7a. Is detected through the monitor laparoscopic probe 7b, and the effect of treatment can be confirmed. At this time, simultaneously with the 1.37 THz electromagnetic wave having the absorption peak A (therapeutic electromagnetic wave), the 1.5 THz electromagnetic wave having the absorption peak B as the reference electromagnetic wave is simultaneously irradiated from the laparoscopic probe 7a for monitoring, and the laparoscopic probe 7b for monitoring. If both the 1.37 THz therapeutic electromagnetic wave and the 1.5 THz reference electromagnetic wave are detected at the tip, the 1.5 THz reference electromagnetic wave intensity at the peak B is a time of T ₁ → T ₂ → T ₃ . It can be confirmed through the monitor laparoscopic probe 7b that the number gradually increases as time passes. Alternatively, the treatment electromagnetic wave of 1.37 THz and the reference electromagnetic wave of 1.5 THz may be detected so as to be differentially amplified. As can be seen from FIG. 9, reduced glucose has a strong absorption peak at 1.95 THz in addition to 1.37 THz at room temperature. Further, although not shown, reduced glucose has a strong absorption peak at 2.46 THz, 3.0 THz, 4.17 THz, and 5.13 THz. On the other hand, glucose has a strong absorption peak at 2.17 THz, 2.75 THz, 3.0 THz, 3.4 THz, 3.8 THz, and 4.6 THz in addition to 1.5 THz shown in FIG. These absorption peak data are findings obtained for the first time by the present inventor using terahertz band electromagnetic wave generation means and electromagnetic wave measurement means, but are 1.95 THz, 2.46 THz, 3 for gastric cancer treatment. 0.07 Hz, 4.17 THz, 5.13 THz, or a combination of a plurality of these frequencies as therapeutic electromagnetic waves, 2.17 THz, 2.75 THz, 3.0 THz, 3.4 THz, 3.8 THz, 4.6 THz Any one of these or a combination of a plurality of these frequencies can be used as the reference electromagnetic wave.

  Furthermore, the therapeutic effect determination unit 23 uses not only cancer cells but also microviruses such as specific viruses and specific bacteria using the data stored in the molecular vibration data storage device 15 and the data from the transmitted electromagnetic wave processing means 14. Changes in the intensity of DNA peaks can be measured to detect cell infection.

  Although there are 20 types of amino acids that constitute cellular proteins, all have vibration absorption peaks unique to the terahertz band. Not only the individual vibration spectra of these elements detected by the monitor laparoscope probe 7b, but also the overall vibration of bacteria and cancer cells themselves, and the unique spectrum as a single macromolecule, confirmation of therapeutic effects and screening judgment materials It becomes.

  In the treatment condition control apparatus 1a shown in FIG. 4, the input device 11 is configured by a keyboard, a mouse, a light pen, a flexible disk device, or the like. The target molecule operation executor can specify input / output data and set various data such as the type of disease, the site, and the physical condition of the patient from the input device 11. Furthermore, it is possible to set analysis parameters such as the form of output data from the input device 11, and it is also possible to input instructions such as execution or suspension of calculations. The output device 17 and the display device 16 are constituted by a printer device and a display device, respectively. The display device 16 displays input / output data, molecular vibration analysis results, molecular vibration analysis parameters, and the like, as well as images of the treatment target (organ) captured by the CCD camera 71 of the irradiation laparoscopic probe 7a. The display is controlled by the monitor control unit 86 of the control device 18a. When a terahertz band image sensor such as a bolometer array is provided at the tip of the monitor laparoscopic probe 7b, a transmission image of the treatment target (organ) imaged by the terahertz band image sensor may be displayed on the display device 16. .

  Next, treatment using the target molecule manipulating apparatus according to the first embodiment of the present invention will be described using laparoscopic surgery as an example with reference to FIGS.

(A) First, the location of the treatment target existing in the patient's body is specified. Specifically, as shown in FIG. 4, the laparoscope probe 7a for irradiation is inserted by puncturing a treatment object with a trocar or the like (not shown). In this case, 3 to 4 small incisions of 5 to 20 mm are made on the skin of a living body, and surgical instruments such as special dedicated long forceps and scissors and a thin tube (laparoscope) are inserted from the incised portion. Using other forceps (not shown), carbon dioxide (CO ₂ ) is introduced into the abdominal cavity and pressurized to expand the abdominal cavity as shown in FIG. 4 so that the operation (operation) is facilitated. To. By pressurizing with carbon dioxide gas (CO ₂ ), the abdominal cavity can be projected on the screen of the display device 16. That is, the light generated by the light source 82 is emitted from the tip of the irradiation laparoscopic probe 7a through the light guide 72 shown in FIG. 5, and an image near the tip of the irradiation laparoscopic probe 7a is acquired. The video is acquired by the CCD camera 71, analyzed by the video processing unit 81 shown in FIG. 4, and then displayed on the display device 16. The video displayed on the display device 16 is preferably processed so as to emphasize only a specific color so that the treatment target can be easily identified. For example, it is preferable to perform IHB color enhancement processing, mucosal dynamic image processing, or the like that renders a specific color more clearly. Or you may make it easy to specify a to-be-treated object by irradiating the laser beam of a specific color from a semiconductor laser like a laser microscope.

  (B) Next, the occurrence location of the treatment target is confirmed while observing the image on the display device 16, and the tip of the irradiation laparoscopic probe 7a is brought close to the surface of the treatment target as shown in FIG. The tip of the laparoscopic probe 7b is brought closer to the back surface of the treatment target. That is, the treatment target is sandwiched between the tip of the irradiation laparoscopic probe 7a and the tip of the monitor laparoscopic probe 7b. Alternatively, the tip of the monitor laparoscope probe 7b is inserted into the organ like an injection needle, and the treatment target is sandwiched between the tip of the irradiation laparoscope probe 7a and the tip of the monitor laparoscope probe 7b. Then, the temperature detection terminal 73 and the electromagnetic wave irradiation terminal 74a of the irradiation laparoscopic probe 7a are brought close to the treatment target. The temperature information of the treatment target is detected by the temperature detection terminal 73, analyzed by the temperature signal processing unit 83 shown in FIG. 4, and then displayed on the display device 16. Next, a treatment frequency determination unit based on experimentally obtained molecular vibration data stored in the molecular vibration data storage device 15 or based on molecular vibration data calculated by the molecular vibration analysis unit 21. 22 determines the frequency corresponding to the temperature of the subject to be treated. According to the knowledge of the present inventor, these frequencies are values in the range of about 0.01 THz to 200 THz, preferably about 0.1 THz to 10 THz.

  (C) Next, as shown in FIG. 11, an electromagnetic wave Φ having a frequency determined by the treatment frequency determining unit 22 is irradiated from an electromagnetic wave irradiation terminal 74a provided at the distal end of the irradiation laparoscopic probe 7a, and the object to be treated is irradiated. Resonance vibration is generated in the molecular structure. At this time, the variable stub 87 is driven by the microactuator 88, the impedance at the end of the high-frequency transmission line is adjusted, and the power of the electromagnetic wave Φ is irradiated to the treatment target. A cell constituting a treatment target is covered with a cell membrane, and has a nucleus surrounded by a cytoplasm and a cytoplasm. Organelles such as endoplasmic reticulum, Golgi apparatus (body), lysosome, mitochondria, peroxime, etc. contained in the nucleus and cytoplasm each have a molecular structure, and cell membranes and DNA also have a molecular structure. For this reason, if the cancer cell to be treated is irradiated with an electromagnetic wave having a frequency of molecular vibration unique to it, it is possible to selectively destroy or transform only the molecular structure as a target. For example, if the molecular structure of telomerase is irradiated by irradiating electromagnetic waves with the resonance frequency of telomerase in cancer cells, the telomeres at the end of the DNA will be shortened at every cell division, and cancer cells will not be able to grow, so the expression of cancer will stop . Alternatively, irradiation with an electromagnetic wave having a resonance frequency of a protease such as plasminogen activator or collagenase to destroy the molecular structure of the protease suppresses invasion of cancer cells and formation of metastasis. When bacteria such as Helicobacter pylori are infested with the subject to be treated, the bacteria are excited by the energy of the electromagnetic wave Φ by irradiating the electromagnetic wave Φ with the frequency of molecular vibration unique to the bacteria, Since it is in a resonance vibration state, the cell membrane, flagella, etc. vibrate greatly. Bacteria greatly vibrated by resonance vibration are destroyed or transformed by targeting only the molecular structure constituting the cell, and eventually die.

(D) Since the treatment target is sandwiched between the tip of the irradiation laparoscopic probe 7a and the tip of the monitor laparoscopic probe 7b, the electromagnetic wave emitted from the tip of the irradiation laparoscopic probe 7a passes through the treatment target. Then, it is detected by the tip of the monitor laparoscopic probe 7b. For example, in the case of the treatment of gastric cancer shown in FIG. 9, it is detected that the intensity of the peak A decreases sequentially with the lapse of time T ₁ → T ₂ → T ₃ along with the irradiation of electromagnetic waves, and the effect of the treatment is detected. I can confirm. At this time, simultaneously with the 1.37 THz electromagnetic wave of the absorption peak A (therapeutic electromagnetic wave), the 1.5 THz electromagnetic wave of the absorption peak B is simultaneously irradiated as a reference electromagnetic wave, and 1.37 THz at the tip of the monitor laparoscopic probe 7b. If both the treatment electromagnetic wave and the reference electromagnetic wave of 1.5 THz are detected and the therapeutic effect is confirmed as a change in the absorption spectrum through the transmission electromagnetic wave processing means 14, the reference electromagnetic wave of 1.5 THz at peak B It can be confirmed that the intensity increases sequentially with the passage of time T ₁ → T ₂ → T ₃ . Alternatively, the treatment electromagnetic wave of 1.37 THz and the reference electromagnetic wave of 1.5 THz may be detected so as to be differentially amplified. If a combination of a plurality of frequencies other than this is used and the therapeutic effect is confirmed as a change in the absorption spectrum via the transmitted electromagnetic wave processing means 14, a more accurate therapeutic effect can be confirmed. When irradiating a plurality of electromagnetic waves, the electromagnetic wave generating means 13 corresponds to each natural frequency, and a plurality of electromagnetic waves having different frequencies are simultaneously supplied to the electromagnetic wave irradiation terminal 74a to irradiate the treatment target. Although it is good, similarly to the frequency division division communication, the pulse may be time-divided and irradiated repeatedly from the electromagnetic wave irradiation terminal 74a in a certain order. In addition, since the kinetic energy increases in the treatment target irradiated with the electromagnetic wave Φ when the electromagnetic wave is irradiated, the temperature of the treatment target itself increases. Therefore, the temperature dependence data of the change in the natural frequency of the treatment target measured in advance and stored in the molecular vibration data storage device 15 or the temperature of the molecular vibration calculated by the molecular vibration analysis unit 21 based on the data. Based on the change data, the frequency of the electromagnetic wave Φ irradiated by the treatment frequency determination unit 22 is determined and adjusted by the frequency adjustment device 34. Further, since the terminal impedance of the high-frequency transmission line 70 changes with a change in frequency accompanying a change in temperature, it is preferable to adjust the impedance by driving the variable stub 87 with the microactuator 88. Irradiation of the electromagnetic wave Φ can be performed directly on the display device 16 while observing the movement of the treatment target in situ (in situ monitoring). Therefore, by observing a change in the movement of the treatment target, Can be grasped, and the frequency of the electromagnetic wave Φ irradiated by the frequency adjusting device 34 can be appropriately changed.

  According to the method for manipulating a target molecule according to the first embodiment of the present invention, resonance vibration is generated in the target molecular structure of the treatment target, and only the molecular structure of the treatment target is selectively destroyed or transformed. Can effectively treat diseases caused by abnormal molecular structure. In particular, since the telomerase that makes and compensates for the telomere at the end of the DNA is used as a target molecule and is selectively destroyed, the telomere disappears and the cancer cells gradually become unable to survive, so that the expression of cancer stops. In addition, since a protease such as plasminogen activator or collagenase is used as a target molecule to selectively destroy it, cancer cells can suppress invasion of cancer cells and formation of metastases.

  As described above, when cancer cells are irradiated with electromagnetic waves in the medium wave (MF) band, macromolecules such as cell membranes are destroyed, and the cancer cells fall into necrosis. In the case of necrosis, there is a problem that leukocytes accumulate in the vicinity due to the cell contents that flow out due to cell collapse and an inflammatory reaction occurs, which further causes cancer epidemic. In contrast, the target molecule manipulation method according to the first embodiment of the present invention irradiates a cancer cell target molecule (biological target molecule) with a terahertz band electromagnetic wave, so that the cancer cell undergoes apoptosis. Be guided. In the case of apoptosis, since fragmented cells are phagocytosed by macrophages and processed, it is very effective because it is not accompanied by an inflammatory reaction and hardly invades the living body.

  Moreover, it is possible to target only the molecular structure of microorganisms (bacteria) parasitic on the patient's body, selectively destroy it, and effectively prevent the progression of infectious diseases caused by microorganisms (bacteria).

  Surgery includes laparotomy in which a cancer is taken directly by the surgeon's hand with a wound of about 15 mm, endoscopic surgery in which the cancer is taken with an endoscope (stomach camera), and a hole in the abdomen. There are laparoscopic surgery etc. that open some and take cancer. In the above, laparoscopic surgery has been described. However, the target molecule manipulation method according to the first embodiment is not limited to laparoscopic surgery, and can be applied to various surgical methods other than laparoscopic surgery. Is possible. In the case of lung cancer, the bronchoscope may be structured as shown in FIGS. 5 and 6, and the target object to be treated may be irradiated with electromagnetic waves from the tip of the bronchoscope. Furthermore, a combination of open surgery and laparoscopic surgery, the abdominal wound may be about 7 mm, and laparoscopic-assisted surgery may be performed with the aid of a laparoscope. Strictly speaking, “craniotomy” for widening the skull, “thoracotomy” performed by incising the chest wall and reaching the chest cavity, and “open surgery” performed by incising the abdominal wall and reaching the abdominal cavity In this specification, the term “open surgery” will be used.

  The target molecule manipulation method according to the first embodiment, when using terahertz band electromagnetic waves, is suitable for cases where there is no metastasis in lymph nodes and cancer cells are present on the surface of the organ, considering the penetration depth of the electromagnetic waves It is. For example, in early gastric cancer and colorectal cancer, cancer tissue is excised with an endoscope. Gastric cancer and colorectal cancer polyps have a raised type and a flat type. The raised type polyp is easy to excise, but it is difficult to remove the flat type polyp, and there are many perforation accidents. However, the flat polyp is more likely to be cancerous than the protuberant type, and if it becomes cancerous, it easily infiltrates and metastasizes within a short period of time, so the flat type is a lesion that should be actively endoscopically removed. In order to selectively remove a flat cancer tissue, conventionally, physiological saline or the like is injected into the lower part of the cancer tissue, the mucosa is floated from the lower mucosa, and a ring shape is formed from the tip of the endoscope. A method that surrounds the cancer tissue that has been lifted by pulling out the wire that has been lifted and burned off with a high-frequency current, or a method in which an IT knife is inserted through a small hole near the lifted cancer tissue and an incision is made around the cancer tissue that has been lifted Was used. According to the target molecule manipulation method according to the first embodiment, the cancer tissue is selectively destroyed by selecting the wavelength of the electromagnetic wave without injecting physiological saline or the like into the lower part of the cancer tissue. There is no anxiety such as a drilling accident.

  In addition, even when a part of an organ is removed at a time, as in the case of advanced cancer, by irradiating the surface of the remaining part without being excised, cancer cells are generated in the remaining part. It is possible to prevent.

(Modification of the first embodiment)
The laparoscopic control device 18b of the target molecule manipulating device according to the modification of the first embodiment of the present invention is connected to the drug solution injection unit 75 as shown in FIG. 13 in addition to the hardware configuration shown in FIG. The chemical solution supply unit 85 is provided. As shown in FIGS. 14 and 15, the irradiation laparoscopic probe 7a has a chemical solution injection part 75 in parallel with the CCD camera 71, the light guide 72, the temperature detection terminal 73, and the electromagnetic wave irradiation terminal 74a. This is different from the irradiation laparoscopic probe 7a shown in FIGS. Further, in the irradiation laparoscopic probe 7a according to the modification of the first embodiment, a monolithic integrated circuit 78 is arranged on the distal end side inside the irradiation laparoscopic probe 7a. This is different from the irradiation laparoscopic probe 7a of the target molecule manipulation device shown in FIG. The monolithic integrated circuit 78 is connected to and controlled by the monolithic integrated circuit control unit 13b of the treatment condition control apparatus 1b shown in FIG. The output of the monolithic integrated circuit 78 is connected to the electromagnetic wave irradiation terminal 74a at the tip of the irradiation laparoscopic probe 7a.

  The monolithic integrated circuit 78 shown in FIG. 14 functions as terahertz band electromagnetic wave generation means. The monolithic integrated circuit 78 is supplied with a DC bias, necessary signals, etc. via a power supply wiring 79. The monolithic integrated circuit 78 preferably includes a relatively wide band amplifier circuit and a frequency tuner that generate an electromagnetic wave having a frequency equal to the natural frequency of the molecule to be treated. For the monolithic integrated circuit 78, a terahertz band amplification oscillation element (active element) such as an ideal SIT can be used. The chemical solution injection unit 75 injects the chemical supplied from the chemical solution supply unit 85 into the tissue to be treated. As a drug to be injected, in the case of cancer treatment, in addition to various anticancer agents such as cisplatin, irinotecan, taxotere and taxol, molecular target therapeutic agents such as Iressa (generic name gefitinib), Glipec and Herceptin can be used.

  For example, gefitinib is a drug that suppresses epidermal growth factor receptor (EGFR), which is an angiogenic factor, and is usually taken about 1 tablet a day. It may be injected into the tissue. Gefitinib is a drug that blocks the growth of blood vessels associated with cancer growth and prevents the growth and metastasis of cancer. While there are patients who are dramatically effective, they cause strong side effects and cause many deaths. By administering gefitinib while irradiating an electromagnetic wave having a frequency equal to the natural frequency of EGFR to inhibit EGFR activity or transforming EGFR, more effective treatment is possible while suppressing side effects. . In order to prevent cancer growth / metastasis, gefitinib may be administered orally as usual without injection through the drug solution injection unit 75, and an electromagnetic wave having a frequency equal to the natural frequency of EGFR may be irradiated. In this case, since the EGFR activity can be directly inhibited by irradiation with electromagnetic waves, the dose of internal use can be reduced and side effects can be suppressed. Clinically, gefitinib-effective patients are often mutated by EGFR, but it is possible to induce mutations in EGFR by irradiating electromagnetic waves at the resonance frequency of EGFR. It is.

  By using high-frequency electromagnetic waves of the millimeter wave (EHF) band or higher, particularly terahertz electromagnetic waves, the outer shape of the laparoscopic probe for irradiation 7a and the laparoscopic probe for monitoring 7b is the same as or outside the outer diameter of the injection needle. Since it can be made smaller, the state in which the irradiation laparoscopic probe 7a and the monitoring laparoscopic probe 7b are inserted into the patient's abdomen or the like can be maintained for several days or more, and the burden on the patient can be reduced even if long-term treatment is performed . For this reason, it is possible to perform treatment while confirming the effect of the internally administered drug.

  Gefitinib was initially said to have no effect on normal cells, but in reality it has side effects due to the presence of EGFR in the skin and gastrointestinal tract. For example, the cancer cells are irradiated with terahertz electromagnetic waves such as 1.37 THz, 1.95 THz, 2.46 THz, 3.0 THz, 4.17 THz, 5.13 THz, etc., which are resonance frequencies of reduced glucose contained in cancer cells. Side effects can be suppressed if only the cancer cells have a medicinal effect of gefitinib by locally exciting only to a higher temperature or active state than other normal cells. The advantage that only the target cells can be locally excited to a higher temperature or active state than other normal cells is not limited to the efficacy of gefitinib, but is also effective for various other treatments.

  In addition, when targeting a microorganism (bacteria) that is parasitic on the body of a patient, it is selected according to the type of the target cell. For example, light such as porfimer sodium used for photodynamic diagnosis (PDD) or photodynamic therapy (PDT) so that the treatment target such as bacteria can be fluorescent and the position of the treatment target can be easily identified. Sensitive substances are preferred.

  In FIG. 15, the CCD camera 71, the light guide 72, the temperature detection terminal 73 and the electromagnetic wave irradiation terminal 74a, and the chemical solution injection section 75 are arranged in a line, but need not be arranged in a line, and other arrangements can of course be adopted. .

  According to the target molecule manipulation device according to the modification of the first embodiment of the present invention, electromagnetic waves are generated while injecting a drug having a therapeutic effect on a target treatment target or a drug having a bactericidal effect on microorganisms. Since irradiation is performed, it is possible to more effectively perform molecular operations such as destruction, transformation, and suppression or promotion of the treatment target by electromagnetic wave irradiation. Furthermore, according to the target molecule manipulation device according to the modification of the first embodiment, since a medicine such as a photosensitive substance is injected into the treatment target, it is possible to easily identify the treatment target.

  In addition, the feature that only the target cells are in a higher temperature state or active state than other normal cells is effective for internal treatment, in which the drug solution is not injected into the tissue to be treated from the drug solution injection unit 75, As described above.

(Second Embodiment)
As shown in FIG. 16, the target molecule manipulation device according to the second embodiment of the present invention includes an antenna holding unit 60 and a plurality of antennas (patch antennas) 61 a and 61 b arranged on the wall surface of the antenna holding unit 60. , 61c,..., And electromagnetic waves Φa, Φb, Φc,... Having a frequency equal to the natural frequency of the biological target molecule (pathological biological target molecule) are supplied to the antenna. This is a molecular target therapy device including the electromagnetic wave generation means 13. The antenna holding unit 60 and the plurality of patch antennas 61a, 61b, 61c,... Constitute an antenna array 6. The antenna holding part 60 has a cylindrical shape, and a living body is accommodated inside the cylinder. As shown in FIG. 17, a plurality of patch antennas 61a, 61b, 61c,... Are arranged in a matrix on the inner wall surface of the antenna holding portion 60. As shown in FIG. 18, the plurality of patch antennas 61a, 61b, 61c,... Are connected to the high-frequency transmission line 62, and are connected to the frequency adjusting device 34 and the electromagnetic wave generating device 35 shown in FIG. Has been. As shown in FIG. 17, the electromagnetic waves generated from the electromagnetic wave generator 35 are electromagnetic waves Φa, Φb, Φc,... From the patch antennas 61a, 61b, 61c,. ..Output as .PHI.t. As the high-frequency transmission line 62, a coaxial cable, a strip line, a coplanar line, or the like is used. Others are the same as the configuration shown in FIG. In FIG. 16, the antenna holding unit 60 is a large antenna holding unit 60 into which the entire human body can enter, but it may be a small type in which only arms or legs can enter. Further, the size may be such that one finger can enter.

  In order to perform treatment using the target molecule manipulation device according to the second embodiment of the present invention, first, in FIG. 16, a treatment site such as necrosis or swelling occurring in the skin to be treated is specified, The natural frequency of a biological target molecule (pathogenic biological target molecule) present at the treatment site is measured. The natural frequency may be measured by direct absorption spectrum measurement or Raman spectroscopy, as in the measurement method shown in the first embodiment, and a biological target using a reflectometer or the like. This is possible by measuring the VSWR of the molecule.

  Next, as shown in FIG. 16, the treatment target is placed on the bed 63 and the treatment target is inserted into the antenna holding unit 60. Next, the electromagnetic wave generator 35 generates an electromagnetic wave having a frequency band close to the natural frequency of the biological target molecule present in the treatment target, for example, 0.01 THz to 200 THz, preferably about 0.1 THz to 10 THz. The frequency adjustment device 34 adjusts the frequency to be equal to the natural frequency of the biological target molecule. Next, patch antennas 61a, 61b, 61c,... 61t provided on the inner wall of the antenna array 6 irradiate the object to be treated with electromagnetic waves Φa, Φb, Φc,. Biological target molecules present in the treatment target are excited by the energy of electromagnetic waves equal to the resonance frequency, and are excited by the various organelles such as the cell membrane, nucleus and mitochondria in the cytoplasm, or chromosomes and chromatin in the nucleus. DNA, and further, codons and base molecules constituting DNA are destroyed or transformed, or cell division is stopped. On the other hand, normal cells to be treated have a natural frequency different from that of a biological target molecule, so that they are not excited and do not cause destruction or transformation of cell membranes or stop of cell division.

  According to the target molecule manipulation device according to the second embodiment of the present invention, electromagnetic waves Φa, Φb, having a frequency different from the natural frequency of normal cells and equal to the natural frequency of biological target molecules. .PHI.c,..., .PHI.t is irradiated to the treatment target from the patch antennas 61a, 61b, 61c,... 61t arranged in a matrix on the inner wall surface of the antenna holding unit 60, respectively. For this reason, without destroying normal cells, it is possible to cause the biological target molecule to resonate and selectively excite and destroy only the specific biological target molecule.

  In the target molecule manipulation device shown in FIG. 16, for example, before inserting the treatment target into the antenna holding unit 60, it is preferable to shield in advance a portion that is not the treatment target. Further, it is preferable to adjust the power level according to the depth of the treatment portion from the surface to be treated. Alternatively, a switch is provided for each of the patch antennas 61a, 61b, 61c,... 61t so that electromagnetic waves are selectively emitted only from the specific patch antennas 61a, 61b, 61c,. Anyway.

  In addition, although illustration is abbreviate | omitted, in the target molecule operation apparatus which concerns on 2nd Embodiment similarly to the target molecule operation apparatus which concerns on 1st Embodiment, the electromagnetic waves which permeate | transmitted the target molecule, or target It is preferable to provide an operation result measuring means for measuring the electromagnetic wave reflected from the molecule and detecting the change state of the target molecule due to the irradiation of the electromagnetic wave. In this case, as the operation result measuring means, the monitor tubule 7b, which is thinner than the injection needle having an outer diameter of 0.1 mm to 0.4 mm having an electromagnetic wave detection terminal at the distal end for detecting the electromagnetic wave, is placed under or subcutaneously in the sarcoma. It can be measured by injection.

  In general, when an electromagnetic wave is irradiated onto a living tissue, the energy of the electromagnetic wave is absorbed by the tissue, so that a phenomenon in which the electromagnetic wave gradually attenuates as it propagates through the tissue must be taken into consideration. When a living tissue is regarded as a dielectric, an attenuation constant γ when an electromagnetic wave propagates through the tissue is expressed by the following equation.

γ = jω (εμ) ^1/2 {1-j (σ / ωε)} ^1/2 (1)
In equation (1), σ is the electrical conductivity of the tissue, ε is the dielectric constant, μ is the magnetic permeability, and ω is the angular frequency. Since the value of p = σ / ωε is about 0.1 <p <10 in the living tissue, when the real part of the equation (1) is α, the following equation is obtained.

α = ω [(με / 2) {(1 + p ² ) ^1/2 -1}] ^1/2 (2)
In the equation (2), considering the case where the frequency f is high,
α = ω {(με / 2) p} ^1/2 (3)
It becomes. The degree of tissue penetration is expressed using the distance δ at which the power density decays to e ⁻² . δ is given by the reciprocal of α and is called “skin depth” or “penetration depth”. In the formula (3), since δ = 1 / α,
δ = (1 / πfμσ) ^1/2 (4)
Is obtained approximately. Since the living body has the same dielectric constant as that of water, and most of the molecules constituting the living body are considered to be non-magnetic materials, it is estimated that ε _r ≈80 [F / m] and μ _r ≈1 [H / m]. it can. The dielectric constant and permeability in vacuum are ε ₀ ≈8.8542 × 10 ⁻¹² [F / m] and μ ₀ ≈4π × 10 ⁻⁷ [H / m]. In the target molecule manipulating apparatus shown in FIG. 16, using the formula (5), when an electromagnetic wave with a frequency of 3 THz is irradiated on a living body, δ = 70 μm, and when an electromagnetic wave with a frequency of 1.2 THz is irradiated, δ = 115 μm. It will be about. According to the Gandhi et al. Data on the skin of rabbits at 23 GHz and the data calculated from the complex dielectric constant based on Debye relaxation, the penetration depth δ = 231 μm or so when irradiated with an electromagnetic wave having a frequency of 300 GHz. It becomes.

When the object to be treated can be regarded as a dielectric having no conductivity, it is necessary to consider dielectric loss. The dielectric loss is indicated using the complex dielectric constant ε. The normal dielectric constant is a real number, but when using a complex dielectric constant,
ε = ε′−jε ″ (5)
Thus, the real part is a normal dielectric constant and the imaginary part is a term indicating loss. Using this, in the far field region (Fraunhofer region), the attenuation constant α of the plane wave propagating in the material is α≈ (π / λ) · (ε ″ / (ε ′) ^1/2 )・ (6)
It becomes. Since ε ′ and ε ″ are functions of frequency and are not constant values, it is generally difficult to express the attenuation constant α by a mathematical expression over a wide frequency range. However, in a range where these values can be regarded as almost constant. Since the attenuation constant α increases as the frequency used (decrease in wavelength) increases, it can be handled in a manner similar to the penetration depth δ _i shown in equation (4), but is impossible. In general, the loss increases as the frequency increases. If the loss is large, a high-power transmitter is required.

  As described above, it can be seen that when a high-frequency electromagnetic wave of microwaves or higher is irradiated, the penetration depth of the electromagnetic wave reaches only near the body surface. In the target molecule manipulating apparatus shown in FIG. 16, treatment when the treatment target is near the epidermis is preferable.

  In the target molecule manipulation device according to the embodiment of the present invention, it is possible to use an electromagnetic wave having a frequency of 1 THz or less. For example, a low frequency electromagnetic wave of about several tens of kHz is irradiated to a chromosome in a cell. It is also possible to vibrate chromosomes and suppress cell division.

  In consideration of the existence of a plurality of natural frequencies of a biological target molecule with respect to a specific biological target molecule, the electromagnetic wave generating means 13 is similar to that of the first embodiment. A plurality of electromagnetic wave generators 35 may be provided to simultaneously oscillate different frequencies.

(Third embodiment)
As shown in FIG. 19, the target molecule manipulation device according to the third embodiment of the present invention has a blood collection line 93 for collecting blood from a living body to be treated and a blood return line 94 for returning blood to the living body. , An electromagnetic wave irradiation unit (antenna array) 6 that emits electromagnetic waves having a frequency equal to the natural frequency of biological target molecules present in the blood of the blood collection line 93, and an electromagnetic wave irradiation unit ( This is a molecular target therapy device comprising an electromagnetic wave generating means 13 for supplying to an (antenna array) 6. The electromagnetic wave generating means 13 is the same as that shown in FIG.

  As shown in FIG. 19, the blood cleaning apparatus 9 includes a blood collection line 93, an antenna array 6 disposed on the downstream side of the blood collection line 93, and a blood return line 94 disposed on the downstream side of the antenna array 6. The blood collection line 93 includes a blood collection port 91, a blood flow pump 95 disposed on the downstream side of the blood collection port 91, and a chamber 96 disposed on the further downstream side of the blood flow pump 95. The blood return line 94 has a chamber 97 disposed on the downstream side of the antenna array 6, and a blood return port 92 disposed on the downstream side of the chamber 97. The blood collection line 93 and the blood return line 94 are made of silicon tubes. As shown in FIG. 20, an electromagnetic wave irradiation unit (antenna array) 6 is disposed so as to surround the outer circumferences of the tubes of the blood collection line 93 and the blood return line 94. The antenna array 6 is equivalent to an antenna array 6 having the same configuration as that shown in FIGS. 17 and 18 with a smaller inner diameter and length, and a matrix-like patch antenna (not shown) provided on the inner wall surface is a blood collection line 93. And the blood return line 94 is disposed on almost the entire outer periphery of the tube. As shown in FIG. 19, the antenna array 6 is connected to a frequency adjusting device 34 and an electromagnetic wave generating device 35 via a high-frequency transmission line 62. As already described, since the penetration depth of 3 THz electromagnetic wave in blood is about δ = 70 μm, the outer diameter of the tube in this case is preferably 140 μm or less. In order to flow a constant blood flow, a plurality of tubes having an outer diameter of 140 μm or less are bundled, and each tube is irradiated with electromagnetic waves from the electromagnetic wave irradiation unit 6. Alternatively, a honeycomb structured tube having a large number of holes having an inner diameter of about 2δ may be formed, and a patch antenna may be provided on the inner wall of each hole. If the inner diameter of the tube becomes too narrow, it becomes impractical, so that a tube having an inner diameter larger than 2δ may be meandered so that blood passing near the center of the tube collides with the inner wall of the tube multiple times.

  19 and 20 illustrate the antenna array 6 having a relatively short length. However, in order to increase the effect of irradiation, it is only necessary to configure the long antenna array 6 along the direction of blood flow. Of course. At a high frequency of 10 THz or higher, the properties as far infrared rays become strong. Therefore, irradiation may be performed long along the direction of blood flow with a micromirror array made of silicon or a cylindrical lens for far infrared rays.

In addition, although illustration is abbreviate | omitted, in the target molecule manipulation apparatus which concerns on 3rd Embodiment similarly to the target molecule manipulation apparatus which concerns on 1st Embodiment, the electromagnetic waves which permeate | transmitted the target molecule, or target It is preferable to provide an operation result measuring means for measuring the electromagnetic wave reflected from the molecule and detecting the change state of the target molecule due to the irradiation of the electromagnetic wave. In this case, as the operation result measuring means, a loop antenna arranged oppositely is provided on the downstream side of the antenna array 6 shown in FIGS. 19 and 20, and an electromagnetic wave emitted from one loop antenna is measured. You may make it detect with the other loop antenna.
Next, a procedure for performing treatment using the target molecule manipulation device according to the third embodiment of the present invention will be described with reference to FIG.

  First, the blood collection port 91 is punctured into the artery to be treated, and the blood return port 92 is punctured into the vein of the living body (the subject to be treated). Blood to be treated (living body) is collected from the blood collection port 91 and flows to the chamber 96 via the blood flow pump 95. The blood from which air and foreign matter have been removed in the chamber 96 flows to the side where the antenna array 6 is disposed. Next, the electromagnetic wave generator 35 generates an electromagnetic wave having a frequency equal to the natural frequency of the biological target molecule present in the blood, and the electromagnetic wave is applied to the antenna array 6 via the frequency adjuster 34 and the high frequency transmission line 62. Supply. The antenna array 6 supplied with the electromagnetic wave irradiates the electromagnetic wave toward the blood from the outer periphery of the blood collection line 93 and the blood return line 94. Biological target molecules in the blood irradiated with electromagnetic waves generate resonance vibrations when given kinetic energy, and various organelles such as cell membranes, nuclei and mitochondria in the cytoplasm, or chromosomes and chromatin in the nucleus. DNA, and further, codons and base molecules constituting DNA are destroyed or transformed, and cell division is stopped. On the other hand, normal cells in blood have a natural frequency different from that of biological target molecules, and thus are not excited and do not cause cell destruction.

  The frequency of the electromagnetic wave supplied from the antenna array 6 is determined based on the target biological target molecule obtained by collecting blood from a living body to be treated in advance and using direct absorption spectrum measurement, Raman spectroscopy, or the like. It can be determined by measuring the natural frequency.

  According to the target molecule manipulation device according to the third embodiment of the present invention, the biological target molecules existing in the blood are selectively excited and destroyed without destroying normal cells in the blood. can do. As in the first and second embodiments, the electromagnetic wave generator 13 may include a plurality of electromagnetic wave generators 35 and simultaneously oscillate different frequencies.

(Fourth embodiment)
Restriction enzymes that cleave double-stranded DNA are broadly classified into three types depending on essential factors and the mode of cleavage. Among them, type II enzymes are frequently used for gene recombination. The patterns of base sequences recognized by various restriction enzymes are different. The restriction enzyme recognizes the pattern in the DNA and cleaves in the vicinity or within the sequence. There are two types of cut edges, and they are called a blunt end and a sticky end depending on their shapes. Many of the base sequence patterns recognized by type II restriction enzymes are palindrome, and they are the same whether they are read from the 5 'end or the 5' end of their complementary strands. . For example, a restriction enzyme called EcoRI recognizes a base sequence of 5′-GAATTC-3 ′ and makes a break between the first guanine (G) and adenine (A). The restriction enzyme HindIII recognizes the sequence 5′-AAGCTT-3 ′ and makes a break between the first two As. If an enzyme called DNA ligase is used, DNAs having the same end can be connected to each other and genes can be rearranged. However, current gene recombination techniques can only be realized with specific base sequence patterns, and their reproducibility may be low.

  As shown in FIG. 22, the target molecule manipulation device according to the fourth embodiment of the present invention is a micro TAS provided with an actuator substrate 101 and a cover glass (not shown). As the actuator substrate 101, a semiconductor substrate such as silicon (Si) can be used. On the surface of the actuator substrate 101, cells such as lymphocytes taken out from a living body are injected together with a Ringer solution, and a biomolecule to be processed is temporarily stored. A tank 111b, a restriction enzyme injection tank 111c for injecting a restriction enzyme with a Ringer solution and temporarily storing it, a base sequence (codon) and a ligase to be newly incorporated together with a Ringer solution and temporarily storing a ligase injection tank 111a for processing A discharge tank 114 for temporarily storing and discharging the cells and Ringer's solution after completion of the process is formed. Between the biological molecule injection tank 111b to be treated and the discharge tank 114, a width of 1 μm to 1 mm, preferably a width of several μm to several hundred μm, a depth of 1 μm to several hundred μm, preferably a depth of several μm to several tens of μm. Channels (microchannels) 116a to 116f are formed, and the cells separated and collected from the living body flow through the channels (microchannels) 116a to 116f together with the Ringer solution. “Ringer solution” is a liquid used to maintain cells in a living state in vitro, and includes ions of sodium, potassium, calcium, and chlorine. An inlet-side microvalve 112b and an inlet-side micropump 113b are disposed in the flow path 116a in the vicinity of the biological molecule injection tank 111b to be processed. A restriction enzyme flow path 116b, which is a micro flow path, is connected to the restriction enzyme injection tank 111c. An inlet side microvalve 112c and an inlet side micropump 113c are arranged in the restriction enzyme channel 116b in the vicinity of the restriction enzyme injection tank 111c. A ligase flow path 116e, which is a micro flow path, is connected to the ligase injection tank 111a. An inlet-side microvalve 112a and an inlet-side micropump 113a are disposed in the ligase channel 116e in the vicinity of the ligase injection tank 111a. An outlet-side microvalve 115 is disposed in the flow path 116 f in front of the discharge tank 114.

As a material of the actuator substrate 101, a semiconductor substrate such as a Si substrate, a glass substrate such as quartz glass, a ceramic substrate such as alumina (Al ₂ O ₃ ), a substrate made of a plastic (polymer material) such as acrylic, or a metal A board | substrate etc. are employable. In view of the ease of microfabrication by photolithography technology and the applicability of MEMS technology, semiconductor substrates, glass substrates, ceramic substrates, and the like are preferable. However, depending on the substrate material, laser machining other than the photolithography technique, electromagnetic wave machining, electric discharge machining, plasma machining, diamond machining, and the like can be applied. For example, when the actuator substrate 101 is a Si substrate, the flow paths (micro flow paths) 116a to 116f are made of an aqueous solution such as potassium hydroxide (KOH) aqueous solution, ethylenediamine aqueous solution, tetramethylammonium hydroxide (TMAH), or the like. It can be formed by anisotropic etching or the like. According to anisotropic etching, in the case of a (100) plane Si substrate, channels (microchannels) 116a to 116f are formed as V-shaped grooves composed of (111) planes that intersect the (100) plane at about 55 °. Can be formed. In addition, U-shaped flow paths (micro flow paths) 116a to 116f having vertical side walls can be formed by various methods such as reactive ion etching (RIE) and ion milling.

  A flow path 116c between the intermediate micro pump 119b and the intermediate micro valve 118c serves as the first target molecule selection operation part (base sequence cutting part), and a flow path 116f between the intermediate micro pump 119e and the intermediate micro valve 118f provides. A second target molecule selection operation unit (base sequence recombination unit) is configured. On both sides of the first target molecule selection operation unit, a first electromagnetic wave generation unit 55a and a first electromagnetic wave detection unit 33a are arranged embedded in the actuator substrate 101, and on both sides of the second target molecule selection operation unit. The second electromagnetic wave generation unit 55b and the second electromagnetic wave detection unit 33b are arranged embedded in the actuator substrate 101. As the electromagnetic wave generators 55a and 55b, a semiconductor crystal such as GaP can be used. The actuator substrate 101 itself may be composed of these semiconductor crystals. A Si bolometer or the like can be used as the electromagnetic wave detectors 33a and 33b.

  As shown in FIG. 22, a restriction enzyme channel 116b through which a restriction enzyme flows joins the collecting channel 116a. That is, an intermediate microvalve 118a and an intermediate micropump 119a are disposed on the downstream side of the region where the first biomolecule analysis unit 107a is disposed in the collecting channel 116a, and a restriction enzyme flow is disposed on the downstream side of the intermediate micropump 119a. The path 116b joins. Furthermore, on the downstream side of the region where the first electromagnetic wave generation unit 55a and the first electromagnetic wave detection unit 33a are arranged in the collective flow channel 116c, a ligase flow channel 116e through which ligase flows is joined. That is, the intermediate micro pump 118c and the intermediate micro pump 119c are arranged on the downstream side of the region where the first electromagnetic wave generating unit 55a and the first electromagnetic wave detecting unit 33a are arranged in the collecting channel 116c. A ligase channel 116e joins downstream of 119c.

  A first agitation tank 117a is disposed in the collecting channel 116c in the vicinity of the junction of the cell channel 116a and the restriction enzyme channel 116b. The first stirring tank 117a can employ a structure in which, for example, a micro screw is driven by a micro actuator. An intermediate microvalve 118b and an intermediate micropump 119b are disposed on the downstream side of the first agitation tank 117a and in the collecting channel 116c near the first agitation tank 117a. Further, a second agitation tank 117b is disposed in the collective flow path 116d near the junction of the collective flow path 116c and the ligase flow path 116e. The second stirring tank 117b can adopt a structure in which a micro screw is driven by a microactuator, similar to the first stirring tank 117a. An intermediate microvalve 118e and an intermediate micropump 119e are disposed in the collective flow path 116d near the second stirring tank 117b on the downstream side of the second stirring tank 117b.

  As shown in FIG. 22, a first biomolecule analysis unit 107a is provided on the downstream side of the inlet-side micropump 113b of the cell channel 116a to distinguish cancer cells, cells affected by viruses and bacteria. An intermediate microvalve 118a is disposed downstream of the first biomolecule analysis unit 107a. Further, an intermediate microvalve 118c and an intermediate micropump 119c are arranged on the downstream side of the first target molecule selection operation unit, and a second biomolecule analysis unit 107b is arranged further on the downstream side thereof. An intermediate microvalve 118d is disposed downstream of the second biomolecule analysis unit 107b. Further, an intermediate microvalve 118f and an intermediate micropump 119f are arranged on the downstream side of the second target molecule selection operation unit, and a third biomolecule analysis unit 107c is arranged on the further downstream side. An outlet side micro valve 115 is arranged in front of the discharge tank 114 on the downstream side of the third biomolecule analysis unit 107c. The first biomolecule analysis unit 107a, the second biomolecule analysis unit 107b, and the third biomolecule analysis unit 107c are CT (computer tomography) portions that obtain a three-dimensional structure of cells. Also good.

  The cross-sectional area after the confluence of the restriction enzyme flow path 116b of the collecting flow path 116c may be about the sum of the cross-sectional areas of the two micro flow paths of the cell flow path 116a and the restriction enzyme flow path 116b. Further, the cross-sectional area of the collecting flow path 116d after the merging point of the ligase flow path 116e is preferably about the sum of the cross-sectional areas of the three micro flow paths, that is, the cell flow path 116a, the restriction enzyme flow path 116b, and the ligase flow path 116e. . However, the microchannels may have a uniform cross-sectional area that is approximately the sum of the cross-sectional areas of the three microchannels from the upstream side.

  As the inlet side micro valves 112a to 112c, the intermediate micro valves 118a to 118f, and the outlet side micro valves 115, diaphragm type (membrane type), piezoelectric element type, electrostatic type, electromagnetic valve type, bimetal / shape memory alloy type, etc. Various microvalves can be used. As the inlet-side micropumps 113a to 113c and the intermediate micropumps 119a to 119f, various micropumps such as a piezoelectric element type, an electrostatic type, an electromagnetic valve type, and a bimetal / shape memory alloy type can be used. Furthermore, a micropump that utilizes the temperature dependence of fluid saturation vapor pressure due to thermal expansion or heating and a change in specific volume due to a phase change, a micropump that applies a magnetic field to a magnetic fluid, and between an electric field generated in a high field It is also possible to use an EHD pump using a special interaction of

  Although not shown in FIG. 22, a cover glass is bonded to the actuator substrate 101 by a bonding method (direct bonding method) or the like. The cover glass has a cell inlet, a restriction enzyme inlet, and a ligase injection corresponding to the positions of the biological molecule injection tank 111b, the restriction enzyme injection tank 111c, the ligase injection tank 111a, and the discharge tank 114 of the actuator substrate 101. An inlet and an outlet are provided. These cell injection port, restriction enzyme injection port, ligase injection port, and discharge port may be opened in the crow substrate by chemical etching, or may be opened by a laser drill. The actuator substrate 101 and the cover glass are bonded by, for example, a bonding method (direct bonding method) such as an anode fusion method in which a voltage is applied while heating to bond.

The target molecule manipulation method according to the fourth embodiment may be performed by the following procedure using the target molecule manipulation apparatus shown in FIG.
(A) First, molecular vibrations such as adenine (A), thymine (T), guanine (G), cytosine (C) and U (uracil), five base molecules, nucleotides containing them, and codons comprising a combination of nucleotides The molecular vibrations of the base sequence at the position to be cut are determined from the data. As described in the first embodiment, these molecular vibration data may be experimentally measured in advance using a terahertz band measurement technique. Alternatively, values calculated from molecular vibration theory based on experimentally obtained data may be used. A base sequence (codon) to be newly incorporated is also prepared at the cut position. The molecular vibration of the base sequence to be newly incorporated is also experimentally measured in advance using a terahertz band measurement technique or calculated from molecular vibration theory. At this time, if there are corresponding restriction enzymes and ligases, they are prepared. When these preparations are completed, cells such as lymphocytes are separated and collected from the living body.

  (B) Next, in a state where the inlet side micro valve 112b of the target molecule manipulating apparatus shown in FIG. 22 is closed, the cells separated and collected from the living body are injected into the biological molecule injection tank 111b to be treated together with the Ringer solution. Further, with the inlet side micro valve 112c closed, the restriction enzyme is injected into the restriction enzyme injection tank 111c from the restriction enzyme injection port together with the Ringer solution. Similarly, with the inlet side micro valve 112a closed, a base sequence (codon) to be newly incorporated and a ligase are injected into the ligase injection tank 111a from the ligase injection port together with the ringer solution. Then, with the intermediate microvalve 118a closed, the inlet side microvalve 112b is opened, the inlet side micropump 113b is operated, and the cells from the biological molecule injection tank 111b to be treated together with the Ringer solution are passed through the cell channel 116a. Injection into the first biomolecule analysis unit 107a. In the first biomolecule analysis unit 107a, a three-dimensional structure of the cell is obtained by irradiating light or an electron beam while rotating the cell with a rotary table (not shown), and processing the signal from the detector by computer processing. Get. When the three-dimensional structure of the cell is obtained, with the intermediate microvalve 118b closed, the intermediate microvalve 118a is opened, the intermediate micropump 119a is activated, and the cells are collected together with the Ringer solution further downstream of the cell channel 116a. It discharges toward the path 116c.

  (C) On the other hand, with the intermediate microvalve 118b closed, the inlet side microvalve 112c is opened, the inlet side micropump 113c is operated, and the restriction enzyme is transferred from the restriction enzyme injection tank 111c together with the Ringer solution to the restriction enzyme channel 116b. inject. As a result, the cells and the restriction enzyme are mixed in the collecting channel 116c. Thereafter, the first agitation tank 117a is operated with the intermediate microvalve 118b closed, and the restriction enzyme and the cells are sufficiently agitated until they are uniform, and if necessary, agitation culture is performed.

  (D) After the restriction enzyme and the cells are sufficiently agitated, with the intermediate microvalve 118c closed, the intermediate microvalve 118b is opened, the intermediate micropump 119b is activated, and the restriction enzyme is moved downstream of the collecting channel 116c. To be released. At the same time as the restriction enzyme is released downstream of the collecting flow path 116c, the electromagnetic wave generation unit 55 is operated. Then, the cell is irradiated with an electromagnetic wave having a frequency of molecular vibration of a base sequence (codon) at a position to be cut, which has been obtained in advance. As a result, the DNA in the cells in the collecting channel 116c resonates at a specific base sequence and is cut. By irradiating a cell with an electromagnetic wave having a frequency of molecular vibration of a base sequence (codon) at a location to be cleaved, the DNA is cleaved with good reproducibility at the desired location.

  (E) When the DNA is cut by irradiating the cells with electromagnetic waves, the intermediate microvalve 118c is opened with the intermediate microvalve 118d closed, the intermediate micropump 119c is operated, and the DNA cleaved cells are removed by Ringer's solution. At the same time, it moves to the second biomolecule analysis unit 107b. In the second biomolecule analysis unit 107b, a cell whose DNA has been cut is obtained by irradiating light or an electron beam while rotating the cell with a rotary table (not shown) and computer-processing the signal from the detector. To obtain a three-dimensional structure. When the three-dimensional structure of the cell is obtained, with the intermediate microvalve 118e closed, the intermediate microvalve 118d is opened, the intermediate micropump 119d is operated, and the cells cleaved with DNA are further added to the cell channel 116c together with the Ringer solution. It discharges toward the downstream collecting flow path 116d.

  (F) On the other hand, with the intermediate microvalve 118e closed, the inlet side microvalve 112a is opened, the inlet side micropump 113a is operated, and the base sequence (codon) and ligase to be newly incorporated from the ligase injection tank 111a are linked to the ringer. The liquid is poured into the ligase flow path 116e and stored in the second stirring tank 117b. As a result, the DNA-cut cell, the base sequence (codon) to be newly incorporated, and the ligase are mixed in the second stirring tank 117b. Then, with the intermediate microvalve 118e closed, the second agitation tank 117b is operated, and the DNA cleaved cells, the base sequence (codon) to be newly incorporated, and the ligase are sufficiently agitated until they become uniform. Incubate accordingly.

  (G) After the DNA cut cell, the base sequence (codon) to be newly incorporated and the ligase are mixed and generated, the intermediate microvalve 118e is opened with the intermediate microvalve 118f closed, and the intermediate micropump 119e is operated. The recombinant DNA is discharged downstream of the collecting channel 116c. The DNA-cut cell, the base sequence (codon) to be newly incorporated, and the ligase are released downstream of the collecting channel 116c, and at the same time, the second electromagnetic wave generator 55b is operated to generate an electromagnetic wave having a specific frequency obtained in advance. To the recombinant DNA. That is, a cell whose DNA has been cut from the second electromagnetic wave generation unit 55b, and a base sequence (codon) to be newly incorporated, of the frequency corresponding to the molecular vibration of the codon of the DNA cleavage part and the molecular vibration of the codon to be newly incorporated. And irradiate the mixture of ligase. In this case, generally, a plurality of terahertz band electromagnetic waves are simultaneously irradiated. In this case, the intensity of electromagnetic waves in the terahertz band is set to be weaker than the intensity at the time of DNA cleavage so that catalytic energy can be imparted when ligase functions as a codon adhesive. By irradiating electromagnetic waves having a frequency corresponding to the molecular vibration of the codon at the DNA cutting site and the molecular vibration of the codon to be newly incorporated, gene recombination can be achieved with high reproducibility and high yield.

  (H) With the outlet side micro valve 115 closed, the intermediate micro valve 118f is opened, the intermediate micro pump 119f is operated, and the recombinant DNA is sent to the third biomolecule analysis unit 107c together with the Ringer solution. The third biomolecule analysis unit 107c irradiates light or an electron beam while rotating the cell with a rotary table (not shown), and computer-processes the signal from the detector, thereby obtaining a three-dimensional structure of the cell. Get. When the three-dimensional structure of the cell is obtained, the outlet side micro valve 115 is opened, the recombinant DNA is sent to the discharge tank 114 together with the Ringer solution, and discharged from the discharge tank 114 to a predetermined container through the discharge port.

  According to the target molecule manipulation method according to the fourth embodiment, by irradiating the cell with an electromagnetic wave having the frequency of molecular vibration of the base sequence (codon) at the position to be cut, the reproducibility is good at the desired cutting position, The DNA is surely cleaved. Further, by irradiating electromagnetic waves having a frequency corresponding to the molecular vibration of the codon at the DNA cutting site and the molecular vibration of the codon to be newly incorporated, gene recombination can be achieved with high reproducibility and high yield.

  Conventional gene recombination techniques using restriction enzymes and ligases require a long-time treatment of about one day and night only at the stage of gene integration using ligase, and the reliability is poor. The target molecule manipulation method according to the fourth embodiment has an advantage that recombination can be ensured in an extremely short time.

  Furthermore, in the target molecule manipulation method according to the fourth embodiment, an example using a restriction enzyme and a ligase has been shown, but these restriction enzymes and ligases are used auxiliary, and in certain cases Restriction enzymes and ligases may not be used. When a restriction enzyme and ligase are not used, suspension culture such as stirring culture using the first stirring tank 117a and the second stirring tank 117b is not required, so that gene recombination is possible in an extremely short time.

  FIG. 23 is a bird's-eye view of a target molecule manipulating apparatus according to a modification of the fourth embodiment of the present invention, and the first target molecule formed by the flow path 116c between the intermediate micro pump 119b and the intermediate micro valve 118c. A first electromagnetic wave irradiation terminal 152a and a first electromagnetic wave detection terminal 153a are arranged on both sides of the selection operation unit (base sequence cutting unit). Further, the second electromagnetic wave irradiation terminal 152b and the second electromagnetic wave irradiation terminal 152b are arranged on both sides of the second target molecule selection operation unit (base sequence recombination unit) formed by the flow path 116f between the intermediate micropump 119e and the intermediate microvalve 118f. An electromagnetic wave detection terminal 153b is disposed. The electromagnetic wave irradiation terminals 152a and 152b are supplied with terahertz band electromagnetic waves via the microstrip line signal lines 151a and 151b using the actuator substrate 101 as an insulator. Although not shown, a ground plate is provided on the back surface of the actuator substrate 101 so as to constitute a microstrip line. The terahertz band electromagnetic waves detected by the electromagnetic wave detection terminals 153a and 153b are transmitted to an electromagnetic wave detection unit (not shown) such as a Si bolometer via the microstrip line signal lines 154a and 154b using the actuator substrate 101 as an insulator. Led. In FIG. 23, the case where the loop antenna is provided as the first electromagnetic wave irradiation terminal 152a and the second electromagnetic wave irradiation terminal 152b has been described. However, the electromagnetic wave irradiation terminals 152a and 152b are not necessarily limited to the loop antenna. Other means such as a parabolic antenna or a horn antenna may be used. Also, the electromagnetic wave detection terminals 153a and 153b need not be limited to the loop antenna shown in FIG. 23, and a parabolic antenna, a horn antenna or the like can be used, and these antennas are omitted to detect an electromagnetic wave such as a Si bolometer. The part may be disposed on the electromagnetic wave detection terminals 153a and 153b. Alternatively, a terahertz band Schottky diode antenna may be disposed on the electromagnetic wave detection terminals 153a and 153b to directly detect the terahertz band Schottky diode. Others are substantially the same as the target molecule manipulating apparatus shown in FIG.

(Other embodiments)
As described above, the present invention has been described with reference to the case where the target molecule manipulation device is applied to a medical device according to the first to fourth embodiments. However, the description and the drawings constituting a part of this disclosure limit the present invention. It should not be understood to be. From this disclosure, various alternative embodiments, examples and operational techniques will be apparent to those skilled in the art.

  For example, the target molecule manipulation device and the target molecule manipulation method according to the first embodiment have mainly been described for cancer treatment, but may be an apparatus and method for measuring clinical data necessary for cancer treatment, such as cancer cells. It will be apparent from the above description that a screening device for detecting abnormal cells may be used.

  Furthermore, in the first embodiment, the electromagnetic wave irradiation terminal 74a does not need to be provided at the tip of the irradiation thin tube (irradiation laparoscopic probe) 7a, and is provided at the tip of a thin tube similar to the irradiation laparoscopic probe 7a. May be. Furthermore, you may provide the electromagnetic wave irradiation terminal 74a at the front-end | tip of surgical instruments, such as forceps. A configuration may be employed in which the frequency of the electromagnetic wave Φ irradiated from the electromagnetic wave irradiation terminal 74a can be measured by providing a frequency detection terminal or the like at the tip of the irradiation laparoscopic probe 7a.

  In the first embodiment, the irradiation thin tube 7a and the monitoring thin tube 7b have been described as separate bodies. However, the electromagnetic wave irradiation terminal 74a is connected to the tip of the probe whose tip is bifurcated into a U shape or a V shape. A structure in which the electromagnetic wave detection terminal 74b is opposed, or a structure in which the distance between the tips of the two-branched probe in a clamp shape is variable, may be a structure in which the electromagnetic wave irradiation terminal 74a and the electromagnetic wave detection terminal 74b are opposed to each other. For example, an integrated object in which the electromagnetic wave irradiation terminal 74a and the electromagnetic wave detection terminal 74b are arranged to face each other inside the cutting edge of “tweezers” or “Yatsuko-don” may be used.

  Furthermore, in the first embodiment, the method of detecting the electromagnetic wave Φ that has passed through the treatment target is exemplified, but reflection type electromagnetic wave measurement may also be used. In this case, an electromagnetic wave irradiation terminal is provided inside one thin tube. And an electromagnetic wave detection terminal 74b. In the case of reflection-type electromagnetic wave detection, the electromagnetic wave irradiation terminal and the electromagnetic wave detection terminal 74b can also serve as the same terminal (antenna or lens).

  Furthermore, in 1st Embodiment, although CPU12 of the treatment condition control apparatus 1a showed the process by the computer provided with the molecular vibration analysis part 21, the treatment frequency determination part 22, and the treatment effect determination part 23 exemplarily, Of course, humans may perform some or all of the calculations and judgments.

  In the target molecule manipulation device according to the second embodiment, the cylindrical antenna holding unit 60 is exemplified, but it is needless to say that a single-sided irradiation type such as an electric kotatsu or an electric heater may be used.

  In the third embodiment, the blood may be contained in blood cells at the same time that the antenna array 6 irradiates blood with electromagnetic waves.

  Similarly to the fourth embodiment, the target molecule manipulation device according to the third embodiment of the present invention can also be configured by using a micro TAS in which micro devices are combined into one chip. That is, with the micro TAS structure, blood is accurately guided to various tubules by the pressure from the syringe pump, healthy blood is flowed out of the fluid circuit, and the blood violated by microorganisms is collected in the microreactor, and the microorganisms You may make it irradiate the electromagnetic wave of natural frequency. Furthermore, not only blood but also a group of cells are flowed together with Ringer's solution, healthy cells are flushed out of the fluid circuit, and cells that have been violated by microorganisms are collected in a microreactor and irradiated with electromagnetic waves of the natural frequency of the microorganisms. Anyway.

In the first to fourth embodiments, zinc telluride (ZnTe), lithium niobate (LiNbO ₃ ), or the like may be used for the GaP core layer of the electromagnetic wave generator 35. The electromagnetic wave Φ extracted from the electromagnetic wave generator 35 may be obtained by parametric oscillation. In the first to fourth embodiments, it is easy to specify a position where a microorganism (pathogenic microorganism) is present by administering a drug such as a photosensitive substance before the treatment of the living body in advance. Is preferred. As means for specifying the type and location of microorganisms, a nuclear magnetic resonance imaging apparatus (MRI), an optical topography apparatus, a functional MRI (FMRI), a near-infrared optical tomography imaging apparatus (CT), etc. may be used in combination. . It is also possible to perform treatment by generating an electromagnetic wave equal to the natural frequency of abnormal cells generated by microorganism infestation or cell mutation.

  In the first to fourth embodiments, the case where a plurality of electromagnetic wave generators 35 are provided inside the electromagnetic wave generator 13 has been described. However, the electromagnetic wave generator 13 may have a plurality of configurations. In this case, the plurality of electromagnetic wave generating means 13 can oscillate a plurality of frequencies simultaneously.

  Furthermore, the target molecule manipulating device of the present invention connects or incorporates the electromagnetic wave generator 35 described in the first to fourth embodiments to an air purifier such as an air conditioner, so that viruses such as influenza viruses can float on the air. Growth of these viruses and pathogenic bacteria by irradiating electromagnetic waves with a frequency equal to the natural frequency or irradiating electromagnetic waves with a frequency equal to the natural frequency of pathogenic bacteria such as methicillin-resistant Staphylococcus aureus (MRSA)・ You can also lose the ability to infect. Specifically, patch antennas 61a, 61b, 61c,... 61t similar to those in FIGS. 16 and 17 may be incorporated in an air cleaner such as an air conditioner. In addition, for Coxsackie virus which is one of the causes of summer cold, MRSA, which is a typical cause of nosocomial infection, Escherichia coli and black mold, similarly, by irradiating electromagnetic waves with a frequency equal to these natural frequencies, It destroys proteins on the surface of these microorganisms at the molecular level, and is effective as a microorganism control technique in the atmosphere.

  The etiological agent of food poisoning includes bacteria, viruses, chemical substances, natural toxins, etc., but more than 80 percent of them are bacteria. For example, Vibrio parahaemolyticus is a typical food poisoning causative agent along with Salmonella in Japan and has the highest frequency of occurrence as a food poisoning causal organism of the endotoxin type. Vibrio parahaemolyticus makes seawater the most suitable habitat, so it proliferates in the summer when the seawater temperature rises, and contaminates marine seafood at a high frequency. Humans who consume contaminated seafood may develop symptoms such as diarrhea, abdominal pain, fever, and vomiting, and may even die. For example, patch antennas 61a, 61b, 61c,... 61t similar to those shown in FIGS. 16 and 17 are arranged inside a refrigerator, a food storage, or a cooking table, so that the natural vibrations of food poisoning bacteria If an electromagnetic wave irradiation unit having a frequency equal to the number is provided, it is possible to selectively kill food poisoning causative bacteria.

  As described above, the present invention naturally includes various embodiments not described herein. Accordingly, the technical scope of the present invention is defined only by the invention specifying matters according to the scope of claims reasonable from the above description.

  The “living body” means a living body of living organisms, and includes all animals and plants that perform living phenomena. In particular, abnormalities caused by microbial infestation or cell mutations in vertebrate cartilage, teleosts, amphibians, reptiles, birds, and mammals It can be used to treat cells. For example, if the natural frequencies of avian coronaviruses (chicken infectious bronchitis virus) that belong to the same family as SARS virus and have the same surface structure are examined in advance, these viruses can be selectively killed. is there. Furthermore, it can be used as a medical device in these medical fields. Furthermore, since microorganisms parasitic on plants can be selectively eliminated, it can be used in the fields of agriculture and food processing. Further, it can be used in the field of air purifiers such as air conditioners.

It is a vibration characteristic in the terahertz band of adenine (A), guanine (G), and cytosine (C) that are the basis of the first to fourth embodiments of the present invention. It is a vibration characteristic in the terahertz band of thymine (T) and uracil (U), which are the basis of the first to fourth embodiments of the present invention. It is a schematic diagram which shows the structure of DNA. 1 is a schematic view of a target molecule manipulation device according to a first embodiment of the present invention. It is sectional drawing of the laparoscopic probe for irradiation which concerns on the 1st Embodiment of this invention. It is the schematic which shows the front-end | tip of the laparoscopic probe for irradiation which concerns on the 1st Embodiment of this invention. It is the schematic which shows the treatment method using the target molecule operation apparatus which concerns on the 1st Embodiment of this invention. It is the schematic which shows the treatment method at the time of using the monitor laparoscopic probe which concerns on the modification of the 1st Embodiment of this invention. It is an absorption spectrum in the terahertz band explaining the effect of cancer treatment using the target molecule manipulation device according to the first embodiment of the present invention. It is the schematic of the electromagnetic wave generator which concerns on the 1st Embodiment of this invention. It is the schematic explaining the electromagnetic wave generation part of the electromagnetic wave generator which concerns on the 1st Embodiment of this invention. It is the schematic explaining the electromagnetic wave input terminal of the laparoscopic probe for irradiation which concerns on the 1st Embodiment of this invention. It is the schematic of the target molecule operation apparatus which concerns on the modification of the 1st Embodiment of this invention. It is sectional drawing of the laparoscopic probe for irradiation which concerns on the modification of the 1st Embodiment of this invention. It is the schematic which shows the front-end | tip of the laparoscopic probe for irradiation which concerns on the modification of the 1st Embodiment of this invention. It is the schematic which shows the target molecule operation apparatus which concerns on the 2nd Embodiment of this invention. It is sectional drawing along the AA direction of the antenna array which concerns on the 2nd Embodiment of this invention. It is the schematic which shows the inner wall face of the antenna array which concerns on the 2nd Embodiment of this invention. It is the schematic which shows the target molecule operation apparatus which concerns on the 3rd Embodiment of this invention. It is an enlarged view of the target molecule operation apparatus which concerns on the 3rd Embodiment of this invention. It is the schematic of Helicobacter pylori. It is a bird's-eye view which shows the target molecule operation apparatus which concerns on the 4th Embodiment of this invention. It is a bird's-eye view which shows the target molecule operation apparatus which concerns on the modification of the 4th Embodiment of this invention.

Explanation of symbols

1a, 1b ... treatment condition control device 6 ... electromagnetic wave irradiation part (antenna array)
7a: capillary tube for irradiation (laparoscopic probe for irradiation)
7b ... capillary for monitoring (laparoscopic probe for monitoring)
8 ... Laparoscope control device 9 ... Blood washing device 11 ... Input device 12 ... CPU
DESCRIPTION OF SYMBOLS 13 ... Electromagnetic wave generation means 13b ... Monolithic integrated circuit control part 14 ... Transmission electromagnetic wave processing means 15 ... Molecular vibration data storage device 16 ... Display apparatus 17 ... Output device 18a, 18b ... Laparoscope control device 21 ... Molecular vibration analysis part 22 ... Treatment Frequency determining unit 23 ... treatment effect determining unit 33 a ... first electromagnetic wave detecting unit 33 b ... second electromagnetic wave detecting unit 34 ... frequency adjusting device 35 ... electromagnetic wave generating device 41 ... low noise amplifier 42 ... AD converter 43 ... absorption Spectrum analysis unit 49 ... YAG laser 50 ... Optical parametric transmitter 51 ... First pump light 52 ... Second pump light 53a, 53b ... Synthetic light 54 ... Pump light control unit 55 ... Electromagnetic wave generator 55a ... First electromagnetic wave generator 55b ... second electromagnetic wave generator 56 ... incident end face 57 ... outgoing end face 58 ... optical waveguide 60 ... antenna holding part 61a, 6 b, 61c, ... patch antenna 62, 70 ... the high-frequency transmission line 63 ... bed 70b ... high-frequency transmission line (waveguide)
71 ... CCD camera 72 ... Light guide 72 ... Temperature detection terminal 73 ... Temperature detection terminal 74a ... Electromagnetic wave irradiation terminal 74b ... Electromagnetic wave detection terminal 75 ... Chemical solution injection part 77 ... Tube 78 ... Monolithic integrated circuit 79 ... Power supply wiring 80 ... Signal processing part DESCRIPTION OF SYMBOLS 81 ... Video processing part 82 ... Light source 83 ... Temperature signal processing part 85 ... Chemical solution supply part 86 ... Monitor control part 87 ... Variable stub 88 ... Microactuator 91 ... Blood collection port 92 ... Blood collection port 93 ... Blood collection line 94 ... Blood collection line 95 ... Blood flow pump 96, 97 ... Chamber 101 ... Actuator substrate 107a ... 1st biomolecule analysis part 107b ... 2nd biomolecule analysis part 107c ... 3rd biomolecule analysis part 111a ... Ligase injection tank 111b ... Processed biomolecule injection Tank 111c ... Restriction enzyme injection tank 112a-112c ... Inlet side micro valve 113a to 113c ... Inlet side micro pump 114 ... Discharge tank 115 ... Outlet side micro valve 116a ... Cell channel (collection channel)
116b: Restriction enzyme flow path 116c: Cell flow path (collection flow path)
116d ... set channel 116e ... ligase passage 116f ... passage 117a ... first stirred tank 117b ... second stirred tank 118A～118f ... intermediate microvalve 119A～119f ... intermediate micropump H _1, H ₂ ... pinhole M ₁ ˜M ₇ ... reflecting mirrors P ₁ , P ₂ ... λ / 2 wavelength plates Φ, Φa, Φb, Φc,.

Claims (8)

An electromagnetic wave irradiation means for irradiating an electromagnetic wave having a frequency equal to the natural frequency of a biological target molecule in a range of 0.01 THz to 200 THz, and activating, transforming or destroying the target molecule;
Electromagnetic wave generating means for supplying the electromagnetic wave of the frequency to the electromagnetic wave irradiating means;
An operation result measuring means for measuring the electromagnetic wave transmitted through the target molecule or the electromagnetic wave reflected from the target molecule and detecting a change state of the target molecule due to irradiation of the electromagnetic wave. Molecular manipulation device.   The electromagnetic wave irradiation means includes an irradiation thin tube having an outer diameter of 0.1 mm to 20 mm having an electromagnetic wave irradiation terminal for emitting the electromagnetic wave at a tip portion and having a high-frequency transmission line for propagating the electromagnetic wave therein. The target molecule manipulation device according to claim 1.   3. The target molecule manipulation device according to claim 1, wherein the manipulation result measurement unit includes a monitor capillary having an outer diameter of 0.1 mm to 10 mm having an electromagnetic wave detection terminal for detecting the electromagnetic wave at a tip portion. 4. .   The target molecule manipulation device according to any one of claims 1 to 3, wherein the irradiation thin tube further includes a temperature detection unit that detects a temperature of the target molecule.   The said electromagnetic wave generation means is further provided with the frequency control apparatus which changes the frequency of the said electromagnetic wave irradiated to the said biological target molecule following the change of the said natural vibration. The target molecule manipulation device according to claim 1.   The target molecule manipulation device according to any one of claims 1 to 5, wherein the electromagnetic wave generation means can simultaneously generate electromagnetic waves having different frequencies. Cleaving DNA at a desired cleavage site;
Irradiate an electromagnetic wave having a frequency equal to the natural frequency of the end codon present at the end of the cut site or the end base molecule constituting the end codon, and selectively select the end codon or the end base molecule. And a step of connecting another codon to the cleavage site, and changing the base sequence of the DNA.   An electromagnetic wave having a frequency equal to a natural frequency of a codon at the cleavage site or a base molecule constituting the codon is irradiated to selectively excite the codon or the base molecule to cleave the DNA. Item 8. The target molecule manipulation method according to Item 7.

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