Pyrotechnic cell disruption device

Abstract

This pyrotechnic cell disruption device is provided with: a pyrotechnic charge to be ignited which is configured to be burnt upon ignition; and a pressure chamber for housing a cell-containing fluid sample therein, said pressure chamber being configured to be pressurized when the pyrotechnic charge is ignited and burnt.

Description

Technical Field

[0001] The present invention relates to an explosive cell disruption device and an explosive cell disruption method.

Background Art

[0002] Cell disruption, also known as cell lysis, is used to break the outer boundary or cell membrane in order to release intracellular substances such as DNA, RNA, proteins, or organelles from cells. The release of such intracellular substances is important for various types of molecular diagnostics. To give some examples, such diagnostics can include pathogen detection platforms, immunological measurements for point-of-care diagnostics, protein purification for studying protein function and structure, cancer diagnostics, drug screening, mRNA transcriptome determination, and analysis of the composition of specific proteins, lipids, and nucleic acids as individual or complex entities.

[0003] Patent Documents 1, 2, etc. disclose point-of-care devices for detecting nucleic acids. The point-of-care devices disclosed in Patent Documents 1, 2, etc. are adapted to receive a sample and include an extraction chamber containing a lysing solution and a heater for extracting and lysing the sample, and nucleic acids are released by lysing the sample in the extraction chamber.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0005] A small sample size has many advantages, especially when collected from humans or animals. It not only enables less invasive sampling methods but also reduces the risk of contaminating the environment. A small sample size allows for a higher degree of automation. Furthermore, a (small-sized) sample has a low risk of contaminating the sample before testing, a low risk of contaminating the environment, can be safely discarded after the test is completed, and is easier to transport within the device. Additionally, a small sample size is suitable for complying with various regulatory standards for clinical tests. Since the risks associated with a small sample size are lower, handling these samples can enable even technicians with relatively little training. A small sample size works well for disposable point-of-care (POC) devices where size and unit cost are important.

[0006] Other types of samples may be plants and fungi. For example, farmers may want to know which pathogens or biotechnologically produced agents are affecting their crops. Food safety and inspection are other areas where a small sample size is suitable.

[0007] Microfluidic technology involves the handling and manipulation of very small amounts of fluid, such as below microliters, and offers various advantages, such as a small amount of reagent, a high surface area (surface-to-volume ratio), low cost, and easy handling of small amounts of fluid suitable for cell analysis. Also, microfluidic devices have been proposed for cell disruption. However, cell disruption with very small amounts of fluid is associated with various challenges, one of which is how to increase the pressure. Also, in some cell disruption methods, it may be necessary to increase the pressure over a certain short period and then release that pressure for efficiency optimization. However, when performing cell disruption with a hydraulic press, it takes time to increase the pressure and a large device may be required.

[0008] Another factor is heat. Excessive heat over a long period may not be desirable as it can potentially damage proteins that are desired to be extracted from inside the cells, but short-term exposure to heat combined with pressure can have an additional positive effect on cell disruption.

[0009] Also, cell disruption by heat lysis requires a significant amount of power. Additionally, chemical lysis uses strongly alkaline materials such as KOH. Chemical lysing reagents may require an additional step of buffering / neutralization before the lysed sample is suitable for downstream analysis.

Means for Solving the Problems

[0010] According to one aspect of the present invention, a pyrotechnic cell disruption device includes a pyrotechnic charge configured to be ignited and burn upon ignition, and a pressure chamber including an internal space configured to contain a fluid sample containing cells and to be pressurized upon ignition and combustion of the pyrotechnic charge.

Advantages of the Invention

[0011] According to the technology related to the present disclosure, it is possible to provide a technology capable of improving the disruption of cells contained in a fluid sample as compared with the prior art.

Brief Description of the Drawings

[0012]

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Embodiments for Carrying Out the Invention

[0013] The explosive cell disruption device disclosed in each of the embodiments described below includes an explosive charge (gunpowder) configured to be ignited and burn upon ignition, and a pressure chamber configured to contain a fluid sample containing cells and be pressurized upon ignition and combustion of the explosive charge. Further, the explosive cell disruption method disclosed in each embodiment includes containing a fluid sample containing cells in a pressure chamber configured to be pressurized by an explosive charge, and pressurizing the fluid sample contained in the pressure chamber by igniting and burning the explosive charge.

[0014] In this way, by mainly using the fuel gas of pyrotechnic explosives as the pressure source when pressurizing a fluid sample, cell disruption can be achieved in an extremely short time. As a result, cell disruption can be achieved in an extremely short time compared to the case of pressurizing a fluid sample with a hydraulic press. In addition, since excessive heat is not exposed to cells over a long period of time as in the thermal lysis method, damage to cells can be suppressed. Further, unlike the chemical lysis method using chemical substances, cell disruption can be performed without using chemical substances that are not easy to handle.

[0015] In addition, the pyrotechnic cell disruption device according to the present disclosure can include an initiator (igniter) having a housing that houses pyrotechnic explosives. The initiator can preferably use, for example, an initiator for operating an airbag of a vehicle, and performs ignition control of pyrotechnic explosives by receiving supply of operating power from an external power source. The pyrotechnic explosives are not particularly limited, and examples thereof include ZPP (zirconium·potassium perchlorate), ZWPP (zirconium·tungsten·potassium perchlorate), THPP (titanium hydride·potassium perchlorate), lead trinitrate, and the like.

[0016] The fluid sample accommodated in the pressure chamber according to the present disclosure is not particularly limited as long as it is a sample of a fluid containing cells, and is, for example, a cell suspension in which cells are dispersed in a liquid. The cells contained in the fluid sample are not particularly limited, and may be cells collected from humans or animals, or may be plant cells, fungi, or other cells.

[0017] In the present disclosure, the dosage (scale, size) of the fluid sample accommodated in the pressure chamber is not particularly limited, and for example, an extremely small dosage on the order of microliters (μL) can be adopted. For example, the dosage of the fluid sample may be 10 μL or more and 500 μL or less. Further, for example, any one of 20 μL, 50 μL, 100 μL, 150 μL, 200 μL, and 300 μL may be adopted as the upper limit value or the lower limit value in the dosage of the fluid sample. Of course, it is also possible to adopt a dosage of the fluid sample on the order of milliliters (mL) or a larger scale.

[0018] Also, the number of cells contained in the fluid sample is not particularly limited. For example, the number of cells contained in the fluid sample may be 1×10 2 cells / cm 3 or more and 1×10 9 cells / cm 3 or less. Also, for example, any one of 1×10 3 cells / cm 3 , 1×10 4 cells / cm 3 , 1×10 5 cells / cm 3 , 1×10 6 cells / cm 3 , 1×10 7 cells / cm 3 , 1×10 8 cells / cm 3 may be adopted as the upper limit value or the lower limit value of the number of cells contained in the fluid sample.

[0019] The pyrotechnic cell disruption device and the pyrotechnic cell disruption method according to the present disclosure ignite and burn the pyrotechnic charge to pressurize the fluid sample containing the cells accommodated in the pressure chamber, and the time required to disrupt the cells is very short, and the time during which the cells contained in the fluid sample are exposed to heat during pressurization can also be made extremely short. In the pyrotechnic cell disruption device and the pyrotechnic cell disruption method according to the present disclosure, the time during which the cells are exposed to heat during pressurization of the fluid sample is not particularly limited, but for example, it may be 0.1 ms (millisecond) or more and 500 ms or less. Also, for example, any one of 1 ms, 10 ms, 20 ms, 30 ms, 40 ms, 50 ms, 60 ms, 70 ms, 80 ms, 90 ms, 100 ms, 200 ms, 300 ms, 400 ms may be adopted as the upper limit value or the lower limit value of the time during which the fluid sample is exposed to heat during pressurization. Also, the time (disruption process duration) from the start of the operation of the pyrotechnic cell disruption device according to the present disclosure until the disruption process of the cells contained in the fluid sample is completed is not particularly limited, but for example, it may be 0.1 ms or more and 1 s (second) or less. Also, for example, any one of 1 ms, 10 ms, 100 ms, 500 ms may be adopted as the upper limit value or the lower limit value of the disruption process duration.

[0020] The pressure chamber of the explosive cell disruption device according to the present disclosure can accommodate, in addition to the fluid sample, any material other than the fluid sample. Examples of materials other than the fluid sample to be accommodated in the pressure chamber include water, any other liquid, or other materials such as water-absorbing polymers, and these may be filled in the pressure chamber. By doing so, when the explosive charge is ignited and burned to pressurize the inside of the pressure chamber, the pressure shock wave can be smoothed.

[0021] The explosive cell disruption device according to the present disclosure can include an orifice through which the fluid sample is circulated after the fluid sample accommodated in the pressure chamber is pressurized by the combustion gas of the explosive charge. The orifice is a fine passage through which the fluid sample pressurized in the pressure chamber is circulated. The orifice may be, for example, a precision orifice formed as a channel having an orifice diameter and a flow path length that is several times longer than the orifice diameter. The diameter of the orifice can be set to a dimension that allows the fluid sample to flow through and can apply sufficient shear stress to the fluid sample during the flow. The diameter of the orifice can be set to different dimensions according to the size, number, type, etc. of the cells contained in the fluid sample, and may be, for example, 1 μm or more and 500 μm or less. Also, for example, any one of 10 μm, 20 μm, 30 μm, 40 μm, 50 μm, 60 μm, 70 μm, 80 μm, 90 μm, 100 μm, 200 μm, 300 μm, 400 μm may be adopted as the upper limit value or the lower limit value of the diameter of the orifice.

[0022] The pyrotechnic cell crushing device according to the present disclosure can include a pressure release unit that pressurizes a fluid sample contained in a pressure chamber with combustion gas of a pyrotechnic charge and then releases the pressure from the pressure chamber. The pressure release unit can include a pressure release valve that opens the pressure chamber to the external space, a rupture disk, and the like. The pressure value at which the pressure release valve opens, or the pressure value at which the rupture disk ruptures is not particularly limited, but may be set, for example, to a pressure value of 20,000 psi or more and 50,000 psi or less. Further, for example, any one of 25,000 psi, 30,000 psi, 35,000 psi, 40,000 psi, 45,000 psi may be adopted as the upper limit value or the lower limit value of the pressure value at which the pressure release valve opens, or the pressure value at which the rupture disk ruptures.

[0023] Hereinafter, embodiments according to the present disclosure will be described with reference to the drawings. Note that each configuration and their combinations in each embodiment are examples, and within the scope not departing from the gist of the present invention, addition, omission, substitution, and other changes of the configuration are possible as appropriate. The present disclosure is not limited by the embodiments, but is limited only by the claims.

[0024] <First Embodiment> FIG. 1 shows a schematic cross-sectional view according to a first aspect before pressurization of a first pyrotechnic cell crushing device. This first pyrotechnic cell crushing device includes a cylinder body 1 having a piston 2 that pushes a fluid sample 3 through a precision orifice 4 and releases (releases) the sample to atmospheric pressure. The precision orifice 4 is formed inside a separate portion 10 that is adhered or press-fitted to the pressure chamber outlet such as a release (discharge) channel 9. The pressure source is not a hydraulic type, but is generated by igniting a pyrotechnic charge (gunpowder) 5. The pyrotechnic cell crushing device further includes, for example, a cap 6 that enables the device to be opened and closed to fill the device with the fluid sample 3 or to include the pyrotechnic charge 5.

[0025] In a first aspect showing the apparatus before pressurization, a low-pressure space 7 of a pressure chamber 15 may be provided between the piston 2 and the fluid sample 3. After the pyrotechnic charge 5 is ignited, the apparatus assumes a second aspect as shown in FIG. 2. Here, the low-pressure space 7 shown in the aspect according to FIG. 1 changes to a high-pressure space 8 with a smaller volume and a higher pressure. As another aspect, it is also possible not to provide a space between the piston and the sample. Further, the low-pressure space 7 may be filled with various different materials such as liquids, as well as other materials such as water-absorbing polymers. The latter smooths the pressure shock wave to some extent to help achieve the desired cell disruption result. The sample can be filled after removing the cap and the piston, but it is also possible to fill the sample through the release channel 9, particularly after removing the insert including the precision orifice 4.

[0026] The precision orifice 4 generates shear stress when cells pass through the precision orifice 4. Then, the cells are rapidly depressurized after passing through the precision orifice 4. The sample size can be reduced to, for example, up to 150 μL, or alternatively, it can be reduced to, for example, up to 10 μL. It is also possible to have a larger sample size such as 1 milliliter. Considering that the sample size is typically very small, the release time through the precision orifice 4 is very short. The gas, including the gas in the low-pressure space 7 that is rapidly compressed after the ignition of the pyrotechnic charge 5, is heated in a very short time by the compression and is exposed to its heat for only a very short time prior to its release through the precision orifice 4. This time is short enough to prevent damage to the cell material but long enough to assist in the cell disruption process.

[0027] The pyrotechnic charge is housed within a separate pyrotechnic charge chamber housing 16 that also includes a first piston 12. Such a pyrotechnic charge chamber housing 16 can include a first cylinder chamber 13 that houses the pyrotechnic charge 5 and the first piston 12. The first piston 12 is movable relative to the first cylinder chamber 13 under the pressure generated by igniting and combusting the pyrotechnic charge 5. The first piston 12 is connected to a second piston, here the aforementioned piston 2 provided within the pressure chamber 15. The piston 2 is provided within the pressure chamber 15 so as to form one wall of the pressure chamber 15. The first cylinder chamber 13 is provided within the pyrotechnic charge chamber housing 16, at least a portion of which is housed within the pressure chamber 15.

[0028] As described above, the first pyrotechnic cell crushing device D1 according to the first embodiment (see FIGS. 1 and 2) includes a pyrotechnic charge 5 (gunpowder) configured to be ignited and combust upon ignition, a pressure chamber 15 (low-pressure space 7 / high-pressure space 8) configured to house the fluid sample 3 and be pressurized upon ignition and combustion of the pyrotechnic charge 5, and a release channel 9 that connects this pressure chamber 15 (low-pressure space 7 / high-pressure space 8) to the external space. The release channel 9 has a precision orifice 4 configured as a passage for the fluid sample 3. The first pyrotechnic cell crushing device D1 includes a cylinder body 1 having the pressure chamber 15 therein. The cylinder body 1 has, for example, a bottomed cylindrical shape with an open upper end as shown in FIGS. 1 and 2, and a cap 6 is detachable at its open end. The cylinder body 1 may be a housing member having a bottomed cylindrical shape. Also, the pyrotechnic charge chamber housing 16 is integrally fixed, for example, to the inner surface side of the cap 6. Further, in the example shown in FIGS. 1 and 2, the fluid sample 3 is placed on the bottom of the cylinder body 1, whereby the fluid sample 3 is housed within the pressure chamber 15.

[0029] When the first pyrotechnic cell crusher D1 operates, ignition control of the pyrotechnic charge 5 is performed. For example, the pyrotechnic charge 5 burns. Here, the first pyrotechnic cell crusher D1 includes an initiator (igniter) for performing ignition control of the pyrotechnic charge 5, and the pyrotechnic charge 5 and the housing holding it may form part of the initiator. The initiator further has, for example, a wire connected to an external power source, and can perform ignition control of the pyrotechnic charge 5 by receiving operating power from the external power source.

[0030] As described above, in the first pyrotechnic cell crusher D1, the pyrotechnic charge 5 and the first piston 12 are accommodated in the first cylinder chamber 13 formed in the pyrotechnic charge chamber housing 16, at least a part of which is accommodated in the cylinder body 1. Therefore, the pyrotechnic charge chamber housing 16 can also be referred to as the "first cylinder chamber housing" that forms the first cylinder chamber 13. As shown in FIG. 1, in the first mode (before pressurization) of the first pyrotechnic cell crusher D1, the pyrotechnic charge 5 is accommodated in the upper region of the first cylinder chamber 13, and at least a part of the first piston 12 is accommodated in the lower region thereof. As shown in FIG. 1, before the operation of the first pyrotechnic cell crusher D1, the pyrotechnic charge 5 is accommodated in the first cylinder chamber 13 defined by the pyrotechnic charge chamber housing 16 separated from the cylinder body 1 of the pressure chamber 15. Here, the first cylinder chamber 13 can be specified as the "pyrotechnic charge chamber" that accommodates the pyrotechnic charge 5.

[0031] Here, the first piston 12 includes a head portion 121 and a rod portion 122 that extends downward from the head portion 121 and is integral with the head portion 121. A rod insertion hole 161 is formed through the bottom of the pyrotechnic charge chamber housing 16. With the rod portion 122 of the first piston 12 inserted into the rod insertion hole 161, the lower end of the rod portion 122 is connected to a piston 2 (second piston) housed in the pressure chamber 15 (outside the first cylinder chamber 13). The first piston 12 is configured to be movable, for example, along the vertical direction of the first cylinder chamber 13 with the head portion 121 housed in the pyrotechnic charge chamber housing 16. Also, the diameter of the head portion 121 of the first piston 12 may be larger than the diameter of the rod insertion hole 161 so that the head portion 121 does not fall out of the outside of the first cylinder chamber 13.

[0032] Among the pressure chamber 15, the region sandwiched between the bottom of the cylinder body 1 and the piston 2 (second piston) is also referred to as the "second cylinder chamber". The second cylinder chamber in the pressure chamber 15 forms a low-pressure space 7 in the first mode before pressurization (before operation) of the first pyrotechnic cell crushing device D1 (see FIG. 1), and forms a high-pressure space 8 in the second mode (see FIG. 2) after pressurization (after operation) (see FIG. 2).

[0033] When the first explosive cell crusher D1 operates, for example, when ignition control of the explosive charge 5 is performed by an initiator, the explosive charge 5 burns to generate combustion gas, resulting in an increase in pressure within the first cylinder chamber 13. As a result, the head portion 121 of the first piston 12 is pressed under the pressure generated by the combustion of the explosive charge 5, and the first piston 12 moves downward with respect to the first cylinder chamber 13. Along with this, the piston 2 (second piston) connected to the rod portion 122 of the first piston 12 also moves downward (toward the bottom side of the cylinder main body 1) in conjunction. Thereby, the volume of the second cylinder chamber in the pressure chamber 15 decreases, and the second cylinder chamber changes from the low-pressure low-pressure space 7 to the high-pressure high-pressure space 8. As a result, the fluid sample 3 accommodated in the second cylinder chamber (here, the high-pressure space 8) in the pressure chamber 15 is pressurized, and the cells contained in the fluid sample 3 (for example, the outer shell of the cells (such as the cell membrane, cell wall, etc.)) can be crushed. Note that the notation "low-pressure space 7 / high-pressure space 8" in this specification refers to the same space within the pressure chamber 15. That is, before the operation (before pressurization) of the explosive cell crusher D1, it is formed as the low-pressure low-pressure space 7, and after the operation (after pressurization) of the device, it means that the low-pressure space 7 changes to the high-pressure high-pressure space 8, and the same applies to the following embodiments.

[0034] Also, the fluid sample 3 contained in the pressure chamber 15 (high-pressure space 8) pressurized by the piston 2 (second piston) as described above is pushed into the release (discharge) channel 9 communicating with the high-pressure space 8 and discharged to the outside of the apparatus through the release channel 9. The fluid sample 3 that has passed through the release channel 9 is collected in a collection container (not shown) under, for example, atmospheric pressure. Since the diameter of the precision orifice 4 is extremely small, a shear stress is generated when the fluid sample 3 passes through the precision orifice 4, and the shear stress acts on the fluid sample 3. In the present embodiment, by applying the shear stress generated when passing through the precision orifice 4 to the cells contained in the fluid sample 3, the cells can be preferably disrupted. Further, the fluid sample 3 that has passed through the precision orifice 4 is rapidly depressurized by being exposed to atmospheric pressure. As a result, as a result of the rapid expansion of the fluid sample 3, the expansion pressure can promote the disruption of the cells contained in the fluid sample 3. As described above, according to the first pyrotechnic cell disruption device D1, by disrupting the cells contained in the fluid sample 3 and separating intracellular substances such as, for example, DNA, RNA, proteins, or cell organelles from the cells, various cell analyses, cell diagnoses, etc. can be performed.

[0035] And according to the first pyrotechnic cell disruption device D1, as a pressure source for pressurizing the fluid sample 3, it can be obtained by igniting and burning the pyrotechnic charge 5 instead of a hydraulic type. In this way, by operating the pistons (the first piston 12 and the second piston) with the combustion gas generated by the ignition of the pyrotechnic charge 5 (gunpowder), the high-pressure space 8 can be instantaneously formed in the pressure chamber 15, the fluid sample 3 can be rapidly pressurized, and at the same time, it can be discharged to the outside through the precision orifice 4. Thereby, it becomes possible to realize efficient cell disruption in a short time. Further, according to the first pyrotechnic cell disruption device D1, since the pressurization of the fluid sample 3 can be performed in a short time as described above, it is possible to suppress the cells contained in the fluid sample 3 from being exposed to high temperatures for a long time. Thereby, it is possible to preferably suppress the cells contained in the fluid sample 3 from being damaged.

[0036] Furthermore, according to the first explosive cell disruption device D1, since the explosive charge 5 (gunpowder) is used as the pressure source for pressurizing the fluid sample 3, efficient cell disruption can be achieved with a small amount of pressure source. As a result, the compactification of the explosive cell disruption device can be realized. Furthermore, the explosive charge 5 (gunpowder) used as the pressure source for pressurizing the fluid sample 3 can be said to be a material suitable for precise control of the generated pressure (output). Therefore, even if the size of the fluid sample 3 accommodated in the pressure chamber 15 is on the order of microliters, the pressure control when pressurizing the cells contained in the fluid sample 3 can be performed with high accuracy. As a result, it is possible to realize a reduction in the amount of the sample size that could not be achieved with conventional cell disruption devices (for example, French press (registered trademark)). Thus, according to the present embodiment, since the fluid sample 3 can be made extremely small, particularly when collecting cells from a human or an animal, it is possible to collect cells with low invasiveness. In addition, since the sample size can be reduced, the risk of environmental contamination can also be reduced, and more advanced automation is also possible. Furthermore, by reducing the sample size, it becomes easy to handle even for those who are not skilled. Also, the small sample size functions well for disposable point-of-care devices (POC) where size and unit price are important, so it is possible to provide an explosive cell disruption device suitable for point-of-care.

[0037] <Second Embodiment> Figure 3 shows a schematic cross-sectional view according to a first aspect before pressurization of the second pyrotechnic cell disruption device, and Figure 4 shows a schematic cross-sectional view according to a second aspect after pressurization of the second pyrotechnic cell disruption device. The embodiments shown in Figures 3 and 4 are essentially variations of the embodiments shown in Figures 1 and 2. Similar elements are denoted by the same reference numerals. The embodiments according to Figures 3 and 4 do not include a piston, and instead of the piston, they include a deformable diaphragm 14 that divides the low-pressure space 7 and the corresponding high-pressure space 8 into two parts. As a result, the pressure chamber 15 is at least partially defined by a deformable diaphragm 14 configured to deform under the pressure generated by the pyrotechnic charge 5 during ignition and combustion of the pyrotechnic charge 5, as shown in Figure 4. The diaphragm 14 reduces the volume of the pressure chamber during deformation, and as a result, pressurizes the pressure chamber during deformation.

[0038] The pyrotechnic charge chamber housing 16 includes a predetermined break portion (breaking point) 17 at the lower end of the pressure relief channel 18 of the pyrotechnic charge. By dividing the housing into two parts at the diaphragm position, removing the diaphragm, and assembling the housing that holds the diaphragm in place, a fluid sample 3 can be inserted into the devices shown in Figures 3 and 4.

[0039] The advantage of the embodiments shown in Figures 3 and 4 is that since the diaphragm 14 hermetically seals the fluid sample 3 from the pyrotechnic charge 5, it suppresses the mixing of the by-products of the pyrotechnic charge 5 with the fluid sample 3 after ignition. The diaphragm is preferably made of metal, but other materials such as PE, PP, or other plastically deformable polymers or other polymers may also be used. Another option is a composite structure such as a coated cloth or polymer-coated glass that holds the glass together by a polymer coating even when the glass is broken. Also, a bellows-like structure may be beneficial as a diaphragm. A further option is to use a mesh screen that helps capture particles and protect the sample from debris but does not act as a pressure barrier, which is essentially a combination of the embodiments shown in Figures 3 and 5.

[0040] As described above, in the second pyrotechnic cell crushing device D2 according to the second embodiment (see FIGS. 3 and 4), the pyrotechnic charge 5 is accommodated in a separate pyrotechnic charge chamber 11 separated from the pressure chamber 15 formed inside the cylinder main body 1. The pyrotechnic charge chamber 11 is formed inside the pyrotechnic charge chamber housing 16. As shown in FIG. 3, a pressure release channel 18 is provided at the bottom of the pyrotechnic charge chamber housing 16. The pressure release channel 18 is a channel 18 for releasing the pressure generated in the pyrotechnic charge chamber housing 16 during the ignition and combustion of the pyrotechnic charge 5 to the pressure chamber 15 where the diaphragm 14 is disposed. In the second pyrotechnic cell crushing device D2, the pressure chamber 15 is partitioned into two spaces by the diaphragm 14. Of the pressure chamber 15 partitioned by the diaphragm 14, the space on the side of the pyrotechnic charge chamber housing 16 is called the "first internal space S1", and the space on the bottom side of the cylinder main body 1 where the fluid sample 3 is placed is called the "second internal space S2". Note that the first internal space S1 of the pressure chamber 15 does not include the internal space of the pyrotechnic charge chamber housing 16. As shown in FIGS. 3 and 4, the fluid sample 3 is accommodated in the second internal space S2 of the pressure chamber 15. Further, the release channel 9 having the precision orifice 4 is connected to the second internal space S2 of the pressure chamber 15, and the second internal space S2 can communicate with the external space through the release channel 9 having the precision orifice 4.

[0041] In the state before operation (before pressurization) of the second pyrotechnic cell crushing device D2 (the first aspect shown in FIG. 3), the pressure release channel 18 of the pyrotechnic charge chamber housing 16 is not in communication with the first internal space S1 of the pressure chamber 15, and is blocked by a breaking portion 17 formed at the bottom of the pyrotechnic charge chamber housing 16 facing the first internal space S1 (pressure chamber 15). The pressure release channel 18 may be formed, for example, as a recess formed at the bottom of the pyrotechnic charge chamber housing 16, and the breaking portion 17 may be formed by a thinned portion where the pressure release channel 18 is formed. In this case, the breaking portion 17 in the pyrotechnic charge chamber housing 16 is formed as a vulnerable portion that is more vulnerable than other portions. The breaking portion 17 in the pyrotechnic charge chamber housing 16 is disposed facing the first internal space S1.

[0042] When the pyrotechnic charge 5 is ignited and burned during the operation of the second pyrotechnic cell crushing device D2, the pressure in the pyrotechnic charge chamber 11 increases due to the combustion gas generated by the pyrotechnic charge 5, and the breaking portion 17 ruptures. As a result, the pyrotechnic charge chamber 11 and the first internal space S1 of the pressure chamber 15 communicate with each other through the pressure release channel 18, and the combustion gas of the pyrotechnic charge 5 is introduced into the first internal space S1. Thereby, as shown in FIG. 4, the diaphragm 14 deforms from the first internal space S1 side toward the second internal space S2 side, and compared with the state shown in FIG. 3, the volume of the first internal space S1 increases and the volume of the second internal space S2 decreases. As a result, the pressure in the second internal space S2 in which the fluid sample 3 is accommodated increases, and it changes from the low-pressure space 7 to the high-pressure space 8. Although the volume of the first internal space S1 increases compared with the state shown in FIG. 3, since the combustion gas of the pyrotechnic charge 5 flows in through the pressure release channel 18, the first internal space S1 also changes from the low-pressure space 7 to the high-pressure space 8 as the second pyrotechnic cell crushing device D2 operates. Also in this embodiment, 1 real Similar to the embodiment, the cap 6 is detachably provided with respect to the upper end opening of the cylinder body 1, and the pyrotechnic charge chamber housing 16 for accommodating the pyrotechnic charge 5 can be fixed inside the cap 6.

[0043] As described above, when the second pyrotechnic cell disruption device D2 operates, the fluid sample 3 contained in the second internal space S2 of the pressure chamber 15 is pressurized. As a result, the cells contained in the fluid sample 3 can be disrupted. Also, as described above, since the release channel 9 including the precision orifice 4 is connected to the second internal space S2 of the pressure chamber 15, the pressurized fluid sample 3 is pushed into the release channel 9. Then, the shear stress generated when the fluid sample 3 passes through the precision orifice 4 is applied to the fluid sample 3, thereby promoting the disruption of the cells contained in the fluid sample 3. After the fluid sample 3 passes through the precision orifice 4, when it is released to the outside of the device and exposed to the atmospheric pressure, it rapidly decompresses and expands, further promoting cell disruption. The fluid sample 3 that has undergone the cell disruption treatment in this way can be collected in a collection container, similar to the first embodiment. According to the second pyrotechnic cell disruption device D2 in this embodiment, the same effects as those of the first pyrotechnic cell disruption device D1 can be obtained. When the diaphragm 14 is formed of a metal material, for example, aluminum, cast iron, stainless steel, or the like may be used as the material.

[0044] <Third Embodiment> FIG. 5 shows a schematic cross-sectional view according to a first aspect before pressurization of the third pyrotechnic cell disruption device, and FIG. 6 shows a schematic cross-sectional view according to a second aspect after pressurization of the third pyrotechnic cell disruption device. This third embodiment is very similar to the second embodiment except that the diaphragm 14 is completely omitted. Thus, the separate pyrotechnic charge chamber housing 16 is directly open into the pressure chamber during ignition and combustion of the pyrotechnic charge. This embodiment simplifies the loading of the sample into the device and minimizes sealing members and moving parts, but exposes the sample to the by-products of the pyrotechnic charge after ignition. However, this may be acceptable depending on the particular sample and the intracellular molecule of interest, if the intracellular molecule does not chemically interact with the by-products or is contaminated to the extent that appropriate detection / diagnosis is compromised. Also, the chemical interaction with the by-products of the pyrotechnic charge can be advantageously used if the by-products enable / enhance cell lysis. Certain chemicals and surfactants are used alone to lyse cells. Additionally, the heat generated by the pyrotechnic charge can also be advantageous in enabling / enhancing cell lysis. In this device, mechanical disruption can also be utilized by adding hard beads or other projectiles / stirrers to the reaction chamber. Similar to the embodiments of FIGS. 1-4, the same reference numbers are used for like elements in this third embodiment as compared to the first and second embodiments.

[0045] The third pyrotechnic cell disruption device D3 configured as described above (see FIGS. 5 and 6) has no partition in the pressure chamber 15 with a diaphragm or the like. The pressure chamber 15 is formed as a low-pressure space 7 before the operation (before pressurization) of the third pyrotechnic cell disruption device D3. Also, after the operation (after pressurization) of the third pyrotechnic cell disruption device D3, the internal pressure of the pressure chamber 15 rises, changing from the low-pressure space 7 to the high-pressure space 8. Further, as is clear from FIG. 5, the structure of the pyrotechnic charge chamber housing 16 that houses the pyrotechnic charge 5 before the operation (before pressurization) of the third pyrotechnic cell disruption device D3 is the same as that of the second pyrotechnic cell disruption device D2, and a pressure release channel 18 and a rupture part 17 are provided in the pyrotechnic charge chamber housing 16. The pressure release channel 18 is not in communication with the internal space (low-pressure space 7) of the pressure chamber 15 before the operation (before pressurization) of the third pyrotechnic cell disruption device D3. Then, with the operation of the device, the pyrotechnic charge 5 is ignited, and the fragile rupture part 17 ruptures under the pressure of the combustion gas generated by the combustion of the pyrotechnic charge 5. As a result, the pyrotechnic charge chamber housing 16 (pyrotechnic charge chamber 11) directly opens into the pressure chamber 15 (low-pressure space 7), and the pressure inside the pyrotechnic charge chamber housing 16 is released (discharged). Thereby, the pressure chamber 15 in which the fluid sample 3 is housed changes from the low-pressure space 7 to the high-pressure space 8, and the fluid sample 3 is pressurized, so that the cells contained in the fluid sample 3 are disrupted. Further, the fluid sample 3 is pushed into the release (discharge) channel 9 and is subjected to shear stress when passing through the precision orifice 4, thereby promoting cell disruption. The fluid sample 3 that has passed through the release (discharge) channel 9 expands rapidly when discharged under atmospheric pressure, further promoting cell disruption, and is then housed in, for example, a collection container or the like. Also in the third pyrotechnic cell disruption device D3 in the present embodiment, the same effects as those of the first and second pyrotechnic cell disruption devices D1 and D2 can be obtained.

[0046] <Fourth Embodiment> FIG. 7 shows a schematic cross-sectional view according to a first aspect before pressurization of a fourth pyrotechnic cell crushing device, and FIG. 8 shows a schematic cross-sectional view according to a second aspect after pressurization of the fourth pyrotechnic cell crushing device. In contrast to the embodiments shown in FIGS. 1 to 6, the embodiments shown in FIGS. 7 to 8 do not have a precision orifice 4, but include a hermetically sealed pressure chamber 15 that forms a low-pressure space 7 before ignition of the pyrotechnic charge, while exactly the same space forms a high-pressure space 8 after ignition of the pyrotechnic charge, and the latter aspect is shown in FIG. 8. The sample size can be equivalent to that in FIGS. 1 to 6, for example, 1 mL, 150 μL, or 10 μL. In the present embodiment, the fluid sample 3 is provided in a separate sample container 19. Further, in the present embodiment, the container includes a pressure release portion 21 having a pressure release valve 20. The container 19 has sufficient flexibility so that it can be crushed under pressure to pressurize the fluid sample 3. For example, the container may be formed as a sample pouch (see, for example, FIG. 9). Alternatively, when the container 19 is filled entirely with the fluid sample 3 without containing gas, the container may not be crushed by the support of the fluid sample 3, but the container should still have sufficient flexibility to pressurize the sample. Apart from containing the sample, the container 19 can also contain different materials, such as a water-absorbing polymer, which helps to protect the integrity of the container when exposed to the pressure shock wave generated from the combustion of the pyrotechnic charge 5. Conversely, if desired, the container can be configured to rupture under pressure from the pyrotechnic charge. Also, one or more samples (pouches) can be processed simultaneously within the same chamber.

[0047] After being rapidly pressurized during the ignition and combustion of the pyrotechnic charge 5, the fluid sample 3 is exposed to a rapid pressure increase due to the gas pressure generated from the pyrotechnic charge 5, and then the pressure relief valve 20 is opened for an effective time for cell disruption. The opening of the pressure relief valve 20 also typically occurs rapidly, causing a rapid pressure drop over time and facilitating the rupture of the cell membrane by cell expansion. The heat generated by the pyrotechnic charge 5 helps to make the cell membrane vulnerable to rupture and can therefore assist in cell disruption. Various other physical and chemical conditions resulting from the combustion of the pyrotechnic charge 5 can contribute to cell destruction. The composition of the charge (gunpowder) itself, which in some cases may also depend on a combination of an initiator and a gas generator, can be applied to adjust the rate of gas and heat generation. The waste heat can be used for other purposes within a point-of-care (POC) detection system (amplification and detection). The waste gas pressure can be used to move the sample from one location (stage) to another or stored for use in a POC device.

[0048] The concept of the container 19 helps to comply with various regulatory standards for clinical trials as the operator is protected from exposure to the sample. Depending on the material from which the container 19 is formed and the filling amount of the container by the sample, the container can either rupture under pressure or remain intact.

[0049] The fluid sample 3 can be removed from the device by opening the cap 6 or, if the container 19 is configured to rupture, by releasing it through the pressure relief valve 20. Such release of the disrupted cell sample can be achieved by changing (rotating) the orientation of the device and using some residual pressure to release the sample.

[0050] The advantage of this hydrostatic shock is that it minimizes seals and moving parts. It is also possible to provide a spring or configure the housing to elastically deform and rebound to generate a pressure wave that resonates at a specific frequency and amplitude, increasing the degree (range) of cell lysis before the pressure is released (discharged).

[0051] By using pyro cell disruption, sufficient shear stress is generated and sufficiently rapid decompression is obtained, so there is no need to push the sample through the precision orifice 4 in this embodiment. This provides far more advantages than simply replacing a large device such as a French press of the prior art with pyro cell disruption. Specifically, the entire sample preparation and assay can be performed in a single chamber in the device, i.e., a hydrostatic pressure process. This device has a simple structure and the number of components can be reduced. This can not only reduce development and manufacturing costs, but also reduce the risk of mechanical failure and contamination. This can also reduce the required sample volume and / or improve the assay signal by preventing waste of the sample.

[0052] The fourth pyrotechnic cell disruption device D4 configured as described above (see FIGS. 7 and 8) includes a pyrotechnic charge 5 configured to be ignited and burn upon ignition, a pressure chamber 15 (low-pressure space 7 / high-pressure space 8) configured to contain the fluid sample 3 and be pressurized upon ignition and combustion of the pyrotechnic charge 5, and a pressure release unit 21 (pressure release valve 20) configured to release pressure from the pressure chamber 15 after the pressure chamber 15 is pressurized by ignition and combustion of the pyrotechnic charge 5. Further, as is clear from FIG. 7, the structure of the pyrotechnic charge chamber housing 16 that houses the pyrotechnic charge 5 before the operation (before pressurization) of the fourth pyrotechnic cell disruption device D4 is the same as that of the second and third pyrotechnic cell disruption devices D2 and D3. The pyrotechnic charge chamber housing 16 is provided with a pressure release channel 18 and a breakage part 17, and is formed within the pyrotechnic charge chamber housing 16 configured to rupture upon ignition and combustion of the pyrotechnic charge 5 and is housed within a separate pyrotechnic charge chamber 11 separated from the pressure chamber 15. And also in the fourth pyrotechnic cell disruption device D4, similar to the third pyrotechnic cell disruption device D3, during operation, the breakage part 17 ruptures due to the pressure of the combustion gas generated by ignition of the pyrotechnic charge 5, and the pyrotechnic charge chamber housing 16 (pyrotechnic charge chamber 11) directly opens into the pressure chamber 15 (low-pressure space 7). As a result, the combustion gas of the pyrotechnic charge 5 flows out from within the pyrotechnic charge chamber housing 16 into the pressure chamber 15 in which the container 19 holding (containing) the fluid sample 3 is disposed, and the pressure chamber 15 changes from the low-pressure space 7 to the high-pressure space 8. Thereby, the fluid sample 3 contained within the container 19 can be pressurized and the cells contained in the fluid sample 3 can be disrupted.

[0053] Also, in the fourth pyrotechnic cell disruption device D4, for example, the container 19 is formed of a flexible pouch capable of filling (containing) the fluid sample 3, and the pouch is configured not to rupture when exposed to the pressure during ignition and combustion of the pyrotechnic charge. Thereby, the fluid sample 3 filled therein can be suitably pressurized and the cells can be disrupted without destroying the container 19 during the operation of the fourth pyrotechnic cell disruption device D4.

[0054] Also, in the fourth pyrotechnic cell crushing device D4, the pressure release unit 21 has a pressure release valve 20, and the pressure release valve 20 may be a valve body that is automatically opened when, for example, a predetermined time has elapsed after the ignition of the pyrotechnic charge 5 during the operation of the fourth pyrotechnic cell crushing device D4. Alternatively, the pressure release valve 20 of the pressure release unit 21 may be a valve body that is automatically opened when, for example, during the operation of the fourth pyrotechnic cell crushing device D4, the pressure in the pressure chamber 15 (high-pressure space 8) in which the container 19 is accommodated has risen to a predetermined pressure. The set value of the pressure at which the pressure release valve 20 is automatically opened is not particularly limited, but it may be set to be opened when exposed to a pressure of at least 20,000 psi. The set value of the pressure at which the pressure release valve 20 is automatically opened can be appropriately set according to, for example, the amount of the fluid sample 3 accommodated in the container 19, the type of cells contained in the fluid sample 3, and the like. Further, the pressure release valve 20 may be a valve body that can be manually opened. Also, the pressure release unit 21 may have a rupture disk that ruptures when exposed to a predetermined pressure. This rupture disk may be configured to rupture when exposed to a pressure of at least 20,000 psi, for example.

[0055] As described above, when the pressure release valve 20 is opened from the state where the fluid sample 3 accommodated in the pressure chamber 15 (high-pressure space 8) is pressurized under high pressure, a rapid pressure drop occurs in the high-pressure space 8. As a result, the cells contained in the fluid sample 3 rapidly expand, and for example, cell crushing can be promoted by a large shear stress acting on the cells. The material of the container 19 for filling (accommodating) the fluid sample 3 is not particularly limited, and it may be a flexible pouch having flexibility. Alternatively, the container 19 may be formed of a hard material such as resin or glass. In this case, when the pressure chamber 15 changes from the low-pressure space 7 to the high-pressure space 8 due to the combustion gas of the pyrotechnic charge 5, the container 19 may be crushed or broken, so that the internal fluid sample 3 is pressurized.

[0056] <Fifth Embodiment> FIG. 9 shows an exploded view of a fifth pyrotechnic cell disruption device, and FIG. 10 shows a schematic cross-sectional view of the fifth pyrotechnic cell disruption device. The pressure release portion 21 is formed as a rupture disk assembly 22 including a rupture disk 23 as shown in FIG. 10. This rupture disk rapidly releases pressure in a controlled manner and within the time frame necessary to rupture the rupture disk 23. This rupture disk is designed to allow such a time frame necessary to achieve cell disruption. Also, the sample pouch 24 is provided within the sample cage 25. This cage 25 is not always necessary, but it helps to handle the sample pouch 24 carefully and also helps to insert the sample pouch into the pressure chamber 15. The cage also prevents the sample pouch from accidentally blocking the pressure release vent path after the pyrotechnic charge has exploded. If this were to occur, the sample could potentially be aerosolized and blown around. This is further mitigated by the embodiments shown in FIGS. 11 and 12, in which the sample is placed outside the direct path between the gas generated by the pyrotechnic charge and the vent (discharge port). Assembly of the device can be achieved by screwing the pressure chamber 15 containing the sample pouch 24 inserted into the cage 25, together with the gasket 26 and the cap 6, by means of high-strength bolts 27 or other clamping methods. The pyrotechnic charge is provided within an initiator 28 coaxially inserted within the pressure chamber 15. Ignition of the pyrotechnic charge can be achieved by connecting the initiator 28 via its wire 29 to a power source that supplies a voltage sufficient to ignite the pyrotechnic charge within the initiator 28.

[0057] The fifth pyrotechnic cell crusher device D5 in the fifth embodiment is a more specific realization of the concept of the fourth pyrotechnic cell crusher device D4 described in FIGS. 7 and 8. In the fifth embodiment, the same reference numerals are used for the same elements as compared with the fourth embodiment. As shown in FIG. 10, the pressure chamber 15 has a pressure vessel 150, and a hollow portion is provided so as to penetrate the pressure vessel 150 along the vertical direction of the pressure vessel 150. An initiator 28 is attached to a portion where the hollow portion opens at the bottom of the pressure vessel 150 so as to airtightly close the opening. As shown in FIG. 10, the pyrotechnic charge chamber housing 16 of the initiator 28 is disposed facing the inside of the pressure vessel 150.

[0058] The reference numeral 153 shown in FIG. 9 is a cap fastening portion in the pressure vessel 150. In the example shown in FIG. 9, the cap fastening portion 153 is located on the upper side of the pressure vessel 150, and the cap 6 can be detachably attached. Thread holes for inserting high-strength bolts 27 are formed in the cap fastening portion 152, the gasket 26, and the cap 6. By sandwiching the gasket 26 between the pressure vessel 150 and the cap 6 and screwing the high-strength bolts 27 inserted into the respective thread holes, the cap 6 can be integrally fastened to the cap fastening portion 153 of the pressure vessel 150. Conversely, the cap 6 can be detached from the pressure vessel 150 by removing the high-strength bolts 27. When the cap 6 is attached to the pressure vessel 150, an airtight pressure chamber 15 is formed inside the pressure vessel 150.

[0059] The pressure chamber 15 in this embodiment extends along the vertical direction (axial direction) of the pressure vessel 150 and includes a sample container accommodating portion 151 and a pressure channel 30 that are coaxially connected. As shown in FIGS. 9 and 10, the sample container accommodating portion 151 opens at the upper surface of the pressure vessel 150, and the lower end of the sample container accommodating portion 151 is connected to the upper end of the pressure channel 30. The pressure channel 30 and the sample container accommodating portion 151 are cavity portions having, for example, a cylindrical shape. The diameter (cross-sectional area) of the sample container accommodating portion 151 is slightly larger than the diameter (cross-sectional area) of the pressure channel 30. A sample container placement portion 152 is formed by a step extending in the radial direction provided between the connection portion (boundary portion) of the sample container accommodating portion 151 and the pressure channel 30. A single sample pouch 24 or a sample pouch 24 with a cage 25 attached can be placed on the sample container placement portion 152. Thereby, the sample pouch 24 can be stably accommodated in the pressure chamber 15. Note that the cage 25 is, for example, a cage-like member capable of holding a flexible sample pouch 24. Even when the cage 25 is attached to the sample pouch 24, a part of the sample pouch 24 is maintained in an exposed state. In this embodiment, an example of accommodating a fluid sample in a flexible sample pouch 24 is described. However, another container filled with the fluid sample may be placed on the sample container placement portion 152 and accommodated in the sample container accommodating portion 151.

[0060] In addition, inside the initiator 28, within the primer charge chamber housing 16, a primer charge chamber 11 for accommodating the primer charge 5 is formed. The primer charge chamber housing 16 is disposed in the pressure channel 30. The primer charge chamber housing 16 may be formed by a cup member that can be ruptured by energy during ignition and combustion of the primer charge 5, for example. The cup member may be formed by a thin-walled metal member such as aluminum. Thereby, due to the energy during ignition and combustion of the primer charge 5, the primer charge chamber 11 directly opens into the pressure channel 30 within the pressure chamber 15, and the combustion gas of the primer charge 5 can be introduced into the pressure channel 30. The pressure channel 30 functions as a ventilation path for supplying the combustion gas of the primer charge 5 to the sample container accommodating portion 151 when the initiator 28 operates. Note that before the operation of the fifth pyrotechnic cell crushing device D5, the pressure chamber 15 (the pressure channel 30 and the sample container accommodating portion 151) is formed as a low-pressure space 7 with a low pressure.

[0061] As shown in FIGS. 9 and 10, the sample container housing portion 151 is open on the upper surface of the pressure vessel 150, and is configured such that when the cap 6 is attached to the pressure vessel 150, the sample container housing portion 151 is covered by the cap 6. Also, as shown in FIGS. 9 and 10, the cap 6 is provided with a pressure release portion 21. The pressure release portion 21 includes a rupture disk assembly 22 and a pressure release ventilation path 61. The pressure release ventilation path 61 is a ventilation path formed to penetrate the cap 6 in the axial direction. The rupture disk assembly 22 has a pressure release ventilation path 22A connected to the pressure release ventilation path 61, a rupture disk 23 disposed so as to block (close) the middle of the pressure release ventilation path 22A, and the like. The pressure release ventilation path 22A extends so as to penetrate the rupture disk assembly 22 in the vertical direction. When the pressure chamber 15 is pressurized by ignition and combustion of the pyrotechnic charge 5 and then the rupture disk 23 ruptures, the pressure release ventilation paths 61 and 22A communicate the sample container housing portion 151 with the external space and release the pressure in the pressure chamber 15 to the outside. The rupture disk 23 is configured to rupture when the pressure on the primary side, that is, the pressure in the pressure chamber 15, rises to a predetermined pressure. The pressure at which the rupture disk 23 ruptures can be appropriately set according to, for example, the amount of the fluid sample 3 filled in the sample pouch 24, the type of cells contained in the fluid sample 3, and the like. Also, as shown in FIG. 10, in a state where the cap 6 is attached to the pressure vessel 150, the pressure channel 30, the sample container housing portion 151, and the pressure release ventilation paths 61 and 22A are coaxially arranged. More specifically, in a state where the cap 6 is attached to the pressure vessel 150, the pressure channel 30, the sample container housing portion 151, and the pressure release ventilation paths 61 and 22A are coaxially arranged so as to be aligned in a straight line through the central axis of the pressure vessel 150.

[0062] When the fifth pyrotechnic cell disruption device D5 configured as described above activates the initiator 28 to ignite the pyrotechnic charge 5, the internal pressure of the pyrotechnic charge chamber 11 increases due to the combustion gas generated by the combustion of the pyrotechnic charge 5, causing the pyrotechnic charge chamber housing 16 (e.g., the cup member) to crack. As a result, the combustion gas of the pyrotechnic charge 5 is introduced from the pyrotechnic charge chamber 11 into the pressure channel 30 in the pressure chamber 15. Then, the combustion gas of the pyrotechnic charge 5 is introduced into the sample container housing portion 151 of the pressure chamber 15 connected coaxially with the pressure channel 30. As a result, the pressure in the sample container housing portion 151 where the sample pouch 24 is accommodated rapidly increases. Thereby, the sample container housing portion 151 changes from the low-pressure space 7 to the high-pressure high-pressure space 8. Even when the cage 25 is attached, a part of the sample pouch 24 is exposed. Thus, the sample pouch 24 can be exposed to the high pressure in the sample container housing portion 151 that has changed to the high-pressure space 8. As a result, the fluid sample 3 filled in the sample pouch 24 is rapidly pressurized, and the cells contained in the fluid sample 3 can be disrupted. Further, when the rupture disk 23 ruptures when the pressure in the sample container housing portion 151 rises to a predetermined pressure, the sample container housing portion 151 is rapidly depressurized. As a result, the cells contained in the fluid sample 3 filled in the sample pouch 24 rapidly expand. For example, a large shear stress acts on the cells, further promoting cell disruption. In the above example, the pressure release ventilation path 22A of the pressure release portion 21 is blocked by the rupture disk 23 (rupture plate). However, it may be replaced with the pressure release valve 20 described in the fourth embodiment. That is, the pressure release valve 20 may be automatically opened when a predetermined time has elapsed after the ignition of the pyrotechnic charge 5, or the pressure release valve 20 may be automatically opened when the pressure in the pressure chamber 15 rises to a predetermined pressure.

[0063] In addition, in the fifth pyrotechnic cell disruption device D5, since the pressure channel 30 and the sample container housing portion 151 are coaxially arranged, when the initiator 28 is operated to burn the pyrotechnic charge 5, the combustion gas can be smoothly introduced into the sample container housing portion 151 through the pressure channel 30, and the cells contained in the fluid sample 3 filled in the sample pouch 24 can be rapidly disrupted. Further, in the fifth pyrotechnic cell disruption device D5, since the pressure channel 30, the sample container housing portion 151, and the pressure relief ventilation paths 61, 22A are coaxially arranged with the cap 6 attached to the pressure vessel 150, when the rupture disk 23 ruptures after the operation of the initiator 28, the combustion gas can be smoothly discharged to the outside from the pressure chamber 15 (sample container housing portion 151, pressure channel 30) through the pressure relief ventilation paths 61, 22A. As a result, the pressure reduction in the pressure chamber 15 can be performed in a shorter time. Consequently, the cells contained in the fluid sample 3 of the sample pouch 24 expand more rapidly, and cell disruption can be further promoted.

[0064] <Sixth Embodiment> FIG. 11 shows a perspective view of the pyrotechnic cell crusher in the sixth embodiment, and FIG. 12 shows a schematic cross-sectional view of the sixth pyrotechnic cell crusher. This sixth embodiment is very similar to the fifth embodiment. However, the initiator 28 is arranged laterally, and the initiator 28 is connected to the low-pressure space / high-pressure space 7, 8 via the pressure channel 30 in the radial direction of the pressure chamber 15. Compared with the coaxial approach according to FIGS. 9 and 10, the advantage of the lateral approach according to FIGS. 11 and 12 is that after the ignition of the pyrotechnic charge, the sample pouch 24 in the sample cage 25 is not directly exposed to the gas flow from the initiator 28. Also, the pressure channel 30 can cross the low-pressure space / high-pressure space 7, 8 spaced apart beyond one axial end in the combination of the sample pouch 24 and the sample cage 25. On the other hand, the other axial end in the combination of the sample pouch 24 and the sample cage 25 can be placed on the bottom of the pressure chamber 15. Apart from avoiding the direct exposure of the combination of the sample pouch 24 and the sample cage 25 from the gas flow, the pressure generated by the pyrotechnic charge also pushes the combination of the sample pouch 24 and the sample cage 25 towards the bottom of the pressure chamber 15. Thereby, the combination of the sample pouch 24 and the sample cage 25 is firmly held in place, and unwanted movement of the combination of the sample pouch 24 and the sample cage 25 is avoided.

[0065] The sixth pyrotechnic cell crushing device D6 according to the sixth embodiment is a modification of the fifth pyrotechnic cell crushing device D5. In the sixth embodiment, the same reference numerals are used for the same elements as compared with the fifth embodiment. The sixth pyrotechnic cell crushing device D6 has a bottomed cylinder shape for the pressure vessel 150, and a pressure chamber 15 is formed inside thereof. The pressure chamber 15 extends in the first direction and includes a pressurized space portion 155 and a pressure channel 30 that branches from the middle of the pressurized space portion 155 in a second direction different from the first direction and is connected to the pressurized space portion 155. In the examples shown in FIGS. 11 and 12, the pressurized space portion 155 extends along the vertical direction (axial direction, first direction) of the pressure vessel 150, the pressure channel 30 extends in the lateral direction (radial direction) of the pressure vessel 150, and the pressure channel 30 branches from the pressurized space portion 155 in an orthogonal direction. Note that the pressure chamber 15 is formed as a low-pressure space 7 before the operation of the sixth pyrotechnic cell crushing device D6 and is formed as a high-pressure space 8 after the operation.

[0066] Also, the sixth pyrotechnic cell crushing device D6 is provided with the same pressure release portion 21 on the cap 6 as the fifth pyrotechnic cell crushing device D5. The pressure release portion 21 includes a rupture disk assembly 22 and a pressure release vent passage 61. The pressurized space portion 155 has a proximal end and a distal end with respect to the pressure release portion 21, and the distal end 155B is positioned at the bottom portion 157 of the pressure vessel 150. On the other hand, the proximal end of the pressurized space portion 155 opens on the upper surface of the pressure vessel 150, and the pressurized space portion 155 is configured to be covered by the cap 6 when the cap 6 is attached to the pressure vessel 150. Further, in a state where the cap 6 is attached to the pressure vessel 150, the proximal end of the pressurized space portion 155 is configured to be connected to the pressure release vent passage 61. For example, the pressurized space portion 155 and the pressure release vent passage 61 are coaxially arranged through the central axis of the pressure vessel 150.

[0067] The pressurized space portion 155 includes a sample container accommodating portion 156 for accommodating the sample pouch 24 between the connection portion 155C with the pressure channel 30 and the distal end. In other words, the pouch holding portion 156 refers to the region below the connection portion P1 in the pressurized space portion 155. In the present embodiment, the sample pouch 24 with the cage 25 attached can be placed on the bottom 157 of the pressure vessel 150. Of course, a single sample pouch 24 may be placed on the bottom 157 of the pressure vessel 150. Note that the height of the sample container accommodating portion 156 has a dimension equal to or greater than the height of the sample pouch 24, and in a state where the sample pouch 24 is accommodated in the sample container accommodating portion 156, the sample pouch 24 does not protrude toward the connection portion P1 side. That is, the sample pouch 24 can be accommodated in the sample container accommodating portion 156 so that the upper end of the sample pouch 24 is located below the connection portion P1 with the pressure channel 30 in the pressurized space portion 155. Further, as shown in FIGS. 11 and 12, the initiator 28 is attached to the side surface of the pressure vessel 150, and the initiator 28 is arranged laterally so that the primer charge chamber housing 16 of the initiator 28 faces inside the pressure channel 30. That is, the primer charge 5 of the initiator 28 is arranged in the pressure channel 30.

[0068] In the sixth pyrotechnic cell crushing device D6 configured as described above, compared with the same effects as those described in the fifth pyrotechnic cell crushing device D5, the following further effects can be obtained. That is, according to the sixth pyrotechnic cell crushing device D6 according to the present embodiment, the combustion gas generated by the ignition and combustion of the primer charge 5 when the initiator 28 operates is supplied to the pressurized space portion 155 through the pressure channel 30, so that the pressurized space portion 155 changes from the low-pressure low-pressure space 7 to the high-pressure high-pressure space 8. At this time, the pressure due to the combustion gas flowing into the sample container accommodating portion 156 below the connection portion P1 presses the sample pouch 24 with the sample cage 25 attached toward the bottom of the pressure vessel 150, and the pressurized sample pouch 24 can be stably held in the sample container accommodating portion 156. Further, since the upper end of the sample pouch 24 is located below the connection portion P1 in the pressurized space portion 155, it is possible to suppress the sample pouch 24 from being directly exposed to the combustion gas flow from the primer charge 5.

[0069] When the rupture disk 23 in the rupture disk assembly 22 ruptures, the pressure chamber 15 communicates with the external space, and the pressure in the pressure chamber 15 is released (discharged) to the outside through the pressure relief ventilation paths 61 and 22A. At this time, since most of the gas discharged from the pressure chamber 15 to the outside through the pressure relief ventilation paths 61 and 22A does not pass through the sample container accommodating portion 156, the sample pouch 24 can be stably placed on the bottom of the pressure vessel 150 when the pressure in the pressure chamber 15 is released. As a result, for example, it is possible to prevent the sample pouch 24 from moving upward from the sample container accommodating portion 156 or the pressure relief ventilation path 61 from being blocked by the sample pouch 24, and it is possible to prevent the rapid and smooth decompression of the pressure chamber 15 from being hindered. Further, in the present embodiment, although an example in which the fluid sample is accommodated in the flexible sample pouch 24 is described, other containers filled with the fluid sample may be accommodated in the sample container accommodating portion 156.

[0070] <Seventh Embodiment> Figures 13 to 15 show an explosive cell disruption device including a sample chip according to the seventh embodiment. As shown in FIG. 13, the clamp 31 holds the fluid sample 3 in the first recess 33 formed in the substrate 34 and is provided at the upper (top) and lower (bottom) portions of the chip 32 that forms the expansion chamber 36 in the second recess 35 formed in the substrate 34. The explosive charge chamber housing 16 can be integrally formed with one of the clamps 31 or can be provided separately. The pressure release channel 18 may be disposed at the center of the upper portion of the fluid sample 3 when the chip is in the clamping position between the clamps 31. The pressure chamber 15 is sealed against the surroundings (environment) by the clamp and / or the explosive charge chamber housing 16, or a combination thereof. The precision orifice 4 connects the pressure chamber 15 and the expansion chamber 36 to each other. Such a precision orifice 4 can be created, for example, by a groove in the substrate 34 that is closed by a clamp so as to form a closed channel between the pressure chamber 15 and the expansion chamber 36. A thin film can be adhered to the chip 34 to seal the precision orifice 4, the expansion chamber 36, and the pressure chamber 15. A small hole or a fragile portion may be provided in the film for pressurization by the explosive charge. Also, other types of orifices, such as an orifice provided to completely penetrate the substrate 34, can be employed.

[0071] FIG. 14 shows the state before ignition, while FIG. 15 shows the mode after the movement of the fluid sample 3 from the pressure chamber 15 into the expansion chamber 36 after ignition. This shows that the fluid sample 3 shown in black in FIG. 14 is dispersed on the expansion chamber 36 that collects the material from the disrupted cells in FIG. 15.

[0072] As described above, the seventh pyrotechnic cell crushing device D7 according to the seventh embodiment (see FIGS. 13 to 15) includes a substrate 34, a pressure chamber 15 formed by a first recess 33 formed in the substrate 34, and a chip 32 (pyrotechnic cell destruction chip) including an expansion chamber 36 formed by a second recess 35 formed in the substrate 34. In this embodiment, the same reference numerals are used for the same elements as those in the embodiments described above. In the example shown in FIG. 13, the first recess 33 (pressure chamber 15) and the second recess 35 (expansion chamber 36) are formed so as to open on the upper surface side of the substrate 34, and the first recess 33 (pressure chamber 15) and the second recess 35 (expansion chamber 36) are connected by a precision orifice 4 (first channel). The precision orifice 4 may be formed by an opening groove that opens on the upper surface of the substrate 34. Also, in the example shown in FIG. 13, the upper surface of the substrate 34 is covered by a thin top layer film 46. For example, the top layer film 46 may be adhered to the upper surface of the substrate 34, and by sealing the opening grooves for forming the first recess 33, the second recess 35, and the precision orifice 4 with the top layer film 46, the pressure chamber 15, the expansion chamber 36, and the precision orifice 4 can be sealed from the outside. Here, various polymer films can be used for the top layer film 46 and the bottom layer film 47 described later. For example, it may be formed by a composite or laminate of polypropylene (PP), polyethylene (PE), or other thermoplastic resins, and a film imparted with heat shrinkability, hydrophilicity, or hydrophobicity can be used as needed.

[0073] The seventh explosive cell crushing device D7 is further clamped by a pair of clamps 31 respectively arranged on the upper (top) and lower (bottom) parts of the chip 32 (explosive cell destruction chip). The pair of clamps 31 are, for example, high-strength clamps having rigidity and can be detachably assembled to the chip 32. The seventh explosive cell crushing device D7 further has an explosive charge chamber housing 16 forming the explosive charge chamber 11, explosive charges 5 and the like housed in the explosive charge chamber 11, and as shown in FIG. 13, the explosive charge chamber housing 16 is arranged above the first recess 33 (pressure chamber 15) in the chip 32 (substrate 34). The explosive charge chamber housing 16 may be integrally formed with the clamp 31 that clamps the upper side of the chip 32, or may be provided separately.

[0074] Similar to the second to fourth embodiments, a pressure release channel 18 and a fracture part 17 are formed at the bottom of the explosive charge chamber housing 16. The pressure release channel 18 is formed as a recess opening to the outside of the explosive charge chamber housing 16, and the pressure release channel 18 is positioned at the center of the first recess 33 (pressure chamber 15) in the chip 32 (substrate 34). Further, the explosive charge chamber housing 16 is arranged such that the pressure release channel 18 is in close contact with the topmost film 46.

[0075] FIG. 14 shows a cross-sectional view and a plan view of the seventh explosive cell disruption device D7 in a state excluding the clamp in the first mode before pressurization (before ignition of the explosive charge 5), and FIG. 15 shows a cross-sectional view and a plan view of the state excluding the clamp in the second mode after pressurization (after ignition of the explosive charge 5). FIGS. 14 and 15 show a cross-sectional view in the upper row and a plan view in the lower row, respectively. Also, in the plan view shown in the lower row of FIGS. 14 and 15, the upper surface of the substrate 34 is shown through the top layer film 46. Further, before the operation of the seventh explosive cell disruption device D7, the fluid sample 3 is accommodated in the pressure chamber 15 of the chip 32. In FIG. 14, the fluid sample 3 accommodated in the pressure chamber 15 is filled in black. On the other hand, when the seventh explosive cell disruption device D7 operates, the explosive charge 5 is ignited, and combustion gas is generated by the combustion of the explosive charge 5. As a result, the pressure in the explosive charge chamber 11 rises, and the fracture part 17 of the explosive charge chamber housing 16 ruptures (cracks), so that the pressure release channel 18 of the explosive charge chamber housing 16 communicates with the explosive charge chamber 11. As a result, due to the pressure in the explosive charge chamber 11, the portion of the top layer film 46 facing the pressure release channel 18 is broken, and the combustion gas flows into the pressure chamber 15 of the chip 32. Thereby, the pressure chamber 15 in the chip 32 is rapidly pressurized, and the cells contained in the fluid sample 3 accommodated in the pressure chamber 15 are disrupted. Note that a small hole or a fragile part may be provided in advance at the portion of the top layer film 46 facing the pressure release channel 18. Thereby, when the seventh explosive cell disruption device D7 operates, it becomes easier to introduce the combustion gas of the explosive charge 5 into the pressure chamber 15. Pyrotechnics

[0076] Furthermore, when the pressure chamber 15 in the chip 32 is pressurized by the combustion gas of the pyrotechnic charge 5, the fluid sample 3 is pushed into the precision orifice 4, and the fluid sample 3 that has moved into the expansion chamber 36 through the precision orifice 4 is held (collected) in the expansion chamber 36. When the fluid sample 3 passes through the precision orifice 4, a large shear stress acts on the cells contained in the fluid sample 3, promoting cell disruption. Here, the expansion chamber 36 has a larger volume than the pressure chamber 15, and when the fluid sample 3 flows from the pressure chamber 15 into the expansion chamber 36 through the precision orifice 4, the fluid sample 3 is decompressed. According to this, when the fluid sample 3 flows into the expansion chamber 36 through the precision orifice 4, the fluid sample 3 expands rapidly, further promoting cell disruption. In this way, the fluid sample 3 subjected to the cell disruption treatment is collected in the expansion chamber 36. Also, in the chip 32 of the present embodiment, a vent 48 that communicates the expansion chamber 36 with the outside may be formed. The vent 48 can be formed, for example, by a groove that opens on the upper surface of the substrate 34 and an opening in the top layer film 46 formed at a position overlapping the groove. The vent 48 can vent to the outside through the opening in the top layer film 46 and the gap between the top layer film 46 and the clamp 31, and atmospheric pressure can be introduced into the expansion chamber 36. By setting the expansion chamber 36 under atmospheric pressure in this way, the fluid sample 3 transferred from the pressure chamber 15 to the expansion chamber 36 can be decompressed and expanded more rapidly, enabling more efficient disruption of the cells contained in the fluid sample 3.

[0077] In addition, in the present embodiment, a reagent may be added to the fluid sample 3 collected in the expansion chamber 36, and a chemical reaction may be performed in the expansion chamber 36. The reagent added to the fluid sample 3 is a reagent for causing a chemical reaction with the cells after disruption contained in the fluid sample 3, and may be, for example, a reagent for achieving a polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), or any other isothermal amplification-related reaction. Further, the chip 32 in the present embodiment further includes a detection chamber formed in a third recess pattern on the substrate 34, and the expansion chamber 36 and the detection chamber may be connected by a channel. Then, after adding a reagent to the fluid sample 3 in the expansion chamber 36 and performing a chemical reaction, the fluid sample 3 after the reaction process may be discharged from the expansion chamber 36 to the detection chamber through the channel. Also, a plurality of types of reagents may be added to the fluid sample 3 in the expansion chamber 36.

[0078] <Eighth Embodiment> Figures 16 to 18 are very similar to Figures 13 to 15, but show an eighth embodiment that enables downstream processing of disrupted cells on the chip. Similar elements are denoted by the same reference numerals as those used in Figures 13 to 15. This eighth embodiment can be applied, for example, as a point-of-care (POC) device. The first recess 33 in the substrate has a more elongated shape in the present embodiment as shown in Figure 17, while the expansion chamber 36 has an elliptical shape. Following the expansion chamber is a downstream reaction chamber 37 containing a reagent 38 for achieving, for example, a polymerase chain reaction (PCR). Also, an optional vent 39 may be provided and configured to release pressure only partially so that the remaining pressure is maintained. This vent 39 facilitates filling of the chamber 37. It may be a hydrophobic vent hole, and as a result, once the chamber is filled, the vent hole in the hydrostatic lock state no longer acts like a vent hole, and the residual pressure behind the liquid is maintained. Finally, a valve 40 that is opened after the PCR reaction is completed may be provided, whereby the processed sample can be moved into the detection chamber 41.

[0079] As described above, the eighth pyrotechnic cell crushing device D8 according to the eighth embodiment (see FIGS. 16 to 18) is a modification of the seventh pyrotechnic cell crushing device D7 described with reference to FIGS. 13 to 15. FIG. 16 shows a schematic cross-sectional view of the eighth pyrotechnic cell crushing device D8, FIG. 17 shows a cross-sectional view and a plan view of the state excluding the clamp in the first mode before pressurization (before ignition of the pyrotechnic charge 5), and FIG. 18 shows a cross-sectional view and a plan view of the state excluding the clamp in the second mode after pressurization (after ignition of the pyrotechnic charge 5). FIGS. 17 and 18 show a cross-sectional view in the upper part and a plan view in the lower part, respectively. In the plan views shown in the lower parts of FIGS. 17 and 18, the upper surface of the substrate 34 is shown through the top layer film 46. In the present embodiment, the same reference numerals are used for the same elements as in the embodiments described above.

[0080] In the chip 32 of the eighth pyrotechnic cell crusher D8, in addition to the first recess 33 (pressure chamber 15), the second recess 35 (expansion chamber 36), and the precision orifice 4, a reaction chamber 37 formed in the form of a third recess on the upper surface side of the substrate 34 and a detection chamber 41 formed in the form of a fourth recess on the upper surface side of the substrate 34 are further provided. The reaction chamber 37 is connected to the expansion chamber 36 through the second channel 61. Also, the detection chamber 41 is connected to the reaction chamber 37 through the third channel 62. As shown in FIG. 17, the downstream reaction chamber 37 is disposed at the subsequent stage (downstream side) of the expansion chamber 36, and the detection chamber 41 is disposed at the further subsequent stage (downstream side) of the reaction chamber 37. The second channel 61 and the third channel 62 may be formed by grooves opening on the upper surface of the substrate 34, for example. Also, on the upper surface of the substrate 34 in the chip 32, the uppermost layer film 46 that seals the pressure chamber 15, the expansion chamber 36, the precision orifice 4, the reaction chamber 37, the detection chamber 41, the second channel 61, and the third channel 62 is adhered. Also, in the example shown in FIG. 17, on the upper surface of the chip 32, a vent 39 communicating with the third channel 62 and a valve 40 disposed at a position subsequent to the vent 39 in the third channel 62 are provided. The vent 39 can be formed, for example, by a recess opening on the upper surface of the substrate 34 and an opening of the uppermost layer film 46 formed at a position overlapping the recess. The vent 39 can communicate with the outside through the opening of the uppermost layer film 46 and the gap between the uppermost layer film 46 and the clamp 31, and the expansion chamber 36, the reaction chamber 37, etc. Atmosphere (External) can be introduced to these by opening to introduce atmospheric pressure. Also, when the valve 40 is open, atmospheric pressure is introduced into the detection chamber 41 through the vent 39.

[0081] In the eighth pyrotechnic cell disruption device D8 configured as described above, after the fluid sample 3 in which the cells have been disrupted by the ignition and combustion of the pyrotechnic charge 5 is collected in the expansion chamber 36, it can be sequentially transferred to the subsequent reaction chamber 37 and detection chamber 41. In the present embodiment, since the vent 39 is provided in the chip 32, the fluid sample 3 can be easily transferred from the pressure chamber 15 to the expansion chamber 36 and the reaction chamber 37. Further, in the reaction chamber 37 in the present embodiment, a reagent 38 for causing a chemical reaction with the cells after disruption contained in the fluid sample 3 is accommodated. For example, the reagent 38 is a reagent for achieving polymerase chain reaction (PCR). After the PCR reaction is completed in the reaction chamber 37, by opening the valve 40, the fluid sample 3 containing the cells after reacting with the reagent 38 can be transferred to the detection chamber 41 through the third channel 62. Note that in the present embodiment, the reagent 38 accommodated in the downstream reaction chamber 37 is not limited to the reagent for achieving polymerase chain reaction (PCR), and may be, for example, a reagent for performing a reaction related to loop-mediated isothermal amplification (LAMP) or any other isothermal amplification. Also, a plurality of types of reagents may be accommodated in the reaction chamber 37.

[0082] <Ninth Embodiment> FIG. 19 shows an exploded view of the ninth embodiment of the pyrotechnic cell disruption device based on the concept shown in FIGS. 13 to 15. FIG. 19 shows more structural details. The clamp 31 is formed as an upper housing 42, which houses the initiator 28 at one end and has a pressure release portion 21 including a threaded barb connector 43 and an ID tube 44 having a diameter of, for example, 3 / 16 inch at the other end. The chip assembly 45 includes a chip 32, a top layer film 46, and a bottom layer film 47. The top layer film 46 and the bottom layer film 47 sandwich the chip 32 containing the sample provided in the first recess 33 and seal it. Further, a vent 48 can be provided in the chip assembly.

[0083] When the chip assembly 45 is attached, the chip assembly 45 is sandwiched between the silicone gasket 49, the upper housing 42, the lower housing 50, and the gasket 49. The chip assembly 45 is integrated by positioning pins in holes provided at diagonally opposite corners in the upper housing 42 and the lower housing 50.

[0084] FIG. 20 shows a schematic cross-sectional view of the ninth embodiment, showing a pressure release channel 18 and a ventilation channel 51 that releases pressure after the combustion of the pyrotechnic charge.

[0085] As shown in FIGS. 21 and 22, the sample is pushed down through the downward channel 52 and moves along the precision orifice 4 formed in the pattern of the groove channel in the chip 32 sealed (sealed) by the gasket 49, and then moves into the expansion chamber 36 through the upward channel 54. As another method, a precision orifice not formed in the channel of the chip can be used. Such a precision orifice can be formed of other suitable materials such as sapphire, ruby, glass or polymer, and can be adhered or pressed into the recess of the chip. FIG. 22 shows a second aspect after the combustion of the pyrotechnic charge, where the fluid sample 3 is located at the bottom of the expansion chamber 36. Here, the sample currently being processed contains disrupted cells including cell contents released for further processing with reagents and final detection.

[0086] As described above, the ninth pyrotechnic cell disruption device D9 according to the ninth embodiment (see FIGS. 19 to 22) specifies the seventh pyrotechnic cell disruption device D7 with a more specific structure. In this embodiment, the same reference numerals are used for the same elements as compared with the above-described embodiments. As shown in FIGS. 19 and 20, the ninth pyrotechnic cell disruption device D9 includes a chip assembly 45 including a chip 32 configured to include a substrate, a topmost layer film 46 covering the upper surface of the chip 32, and a lowermost layer film 47 covering the lower surface of the chip 32. Note that FIGS. 21 and 22 are schematics of the chip assembly 45 in the ninth pyrotechnic cell disruption device D9. It is a sectional view. In FIG. 21, a first aspect before the combustion of the pyrotechnic charge is shown, and in FIG. 22, a second aspect after the combustion of the pyrotechnic Medicine charge is shown.

[0087] The chip 32 according to the ninth embodiment, similar to the seventh embodiment, has a pressure chamber 15 formed by a first recess 33 on the upper surface of the substrate, and an expansion chamber 36 formed by a second recess 35. Also, as shown in FIG. 19, the chip 32 is provided with a vent 48 communicating with the expansion chamber 36.

[0088] Also, as shown in FIGS. 21 and 22, the pressure chamber 15 and the expansion chamber 36 are connected via a first channel 63. The first channel 63 includes a precision orifice 4, a downward channel 52, a lateral channel 53, an upward channel 54, etc. In the example shown in FIGS. 21 and 22, the upper end of the precision orifice 4 is connected to the bottom of the first recess 33 so that the pressure chamber 15 communicates with the precision orifice 4, and the downward channel 52 connected to the lower end of the precision orifice 4 extends to the lower surface of the chip 32. On the other hand, the upward channel 54 of the first channel 63 has its upper end connected to the bottom of the second recess 35 forming the expansion chamber 36, and is provided so as to extend downward from the bottom of the second recess 35 and reach the lower surface of the chip 32 at its lower end. The downward channel 52 and the upward channel 54 of the first channel 63 may be formed, for example, by holes extending from the lower surface of the substrate 34 toward the upper surface side. And the lateral channel 53 has one end connected to the lower end of the downward channel 52 and the other end connected to the lower end of the upward channel 54. The lateral channel 53 may be formed, for example, by a groove channel opening on the lower surface of the chip 32.

[0089] And in this embodiment, by covering the upper surface of the chip 32 with the top layer film 46, the first recess 33 (pressure chamber 15) and the second recess 35 (expansion chamber 36) that open to the upper surface of the chip 32 can be sealed from the outside. Also, by covering the lower surface of the chip 32 with the bottom layer film 47, the first channel 63 can be sealed from the outside.

[0090] As shown in FIGS. 19 and 20, the ninth pyrotechnic cell crushing device D9 is formed with a pair of rigid clamps 31 in the form of a housing. That is, the pair of clamps 31 includes an upper housing 42 as an upper clamp and a lower housing 50 as a lower clamp. In the example shown in FIG. 19, the upper housing 42 (upper clamp) and the lower housing 50 (lower clamp) are formed as a housing having a substantially rectangular parallelepiped shape. However, the shapes of the upper housing 42 and the lower housing 50 are not particularly limited. Here, on the upper surface side of the lower housing 50 (lower clamp), there is a chip recess 50A capable of accommodating a chip assembly 45 including the chip 32. Also, the lower surface of the upper housing 42 (upper clamp) forms a substantially flat clamp surface 42A facing the loading region of the chip 32p. Further, holes for fitting the connecting pins 64 are provided at the diagonally opposed corners of the upper housing 42 and the lower housing 50, respectively.

[0091] As shown in FIGS. 19 and 20, an initiator 28 is attached to one side surface of the upper housing 42 (upper clamp), and a threaded barb connector 43 of the pressure release portion 21 is attached to the opposite side surface. The initiator 28 includes an initiator charge chamber housing 16 that forms the initiator charge chamber 11, an initiator charge 5 accommodated in the initiator charge chamber 11, a wire 29, and the like. The initiator 28 is fixed to the upper housing 42 such that the initiator charge chamber housing 16 is accommodated inside the upper housing 42 and the wire 29 is exposed to the outside. One end of a pressure release channel 18 is connected to the initiator charge chamber housing 16 of the initiator 28. The pressure release channel 18 is formed by, for example, a metal conduit, and the other end thereof is joined to the clamp surface 42A of the upper housing 42 from the inside. The opening at the other end side of the pressure release channel 18 communicates with the outside of the upper housing 42 through a gas outlet 42B, which is an opening formed in the clamp surface 42A. The pressure release channel 18 is pre-communicated with, for example, the initiator charge chamber 11 of the initiator 28, or is cleaved by the combustion energy of the initiator charge 5, so as to release the combustion gas of the initiator charge 5 from the gas outlet 42B of the clamp surface 42A in the upper housing 42 when the initiator 28 operates. Note that the open end of the pressure release channel 18 and the gas outlet 42B of the clamp surface 42A may be positioned at the center of the first recess 33 (pressure chamber 15) in the chip 32.

[0092] Also, as shown in FIG. 20, an ID tube 44 and a ventilation channel 51 are connected to the threaded valve connector 43 of the pressure relief portion 21. The ID tube 44 is a hollow tube and is arranged outside the upper housing 42. The ventilation channel 51 is formed by, for example, a metal conduit. One end of the ventilation channel 51 is connected to the threaded valve connector 43, and the other end is joined to the clamping surface 42A of the upper housing 42 from the inside. Further, the opening on the other end side of the ventilation channel 51 communicates with the outside of the upper housing 42 through the ventilation port 42C which is an opening formed in the clamping surface 42A. Note that the inside of the threaded valve connector 43 is hollow, and a ventilation path is formed inside the ventilation channel 51, the threaded valve connector 43, and the ID tube 44.

[0093] When the ninth pyrotechnic cell crushing device D9 configured as described above is assembled, the chip assembly 45 is housed in the chip recess 50A of the lower housing 50. At that time, as shown in FIG. 19, the chip assembly 45 is housed in the chip recess 50A in a state of being sandwiched between a pair of gaskets 49. After housing the chip assembly 45 sandwiched between the pair of gaskets 49 in the chip recess 50A, the ninth pyrotechnic cell crushing device D9 can be assembled by integrally fixing the upper housing 42 and the lower housing 50 using the connecting pin 64. However, the connecting structure of the upper housing 42 and the lower housing 50 is not particularly limited.

[0094] When the initiator 28 of the ninth pyrotechnic cell crusher D9 activates, the pyrotechnic charge 5 ignites and burns, and the combustion gas is discharged from the gas outlet 42B formed in the clamp surface 42A in the upper housing 42 through the pyrotechnic charge chamber 11 and the pressure relief channel 18. Here, the top layer film 46 of the chip assembly 45 and the gasket 49 disposed on the upper surface side of the chip assembly 45 are formed with openings for venting the combustion gas discharged from the gas outlet 42B to the pressure chamber 15 of the chip 32. Thereby, the combustion gas from the pressure relief channel 18 flows into the pressure chamber 15, so that the pressure chamber 15 is rapidly pressurized, and the cells contained in the fluid sample 3 accommodated in the pressure chamber 15 are crushed.

[0095] Also, the fluid sample 3 pressurized in the pressure chamber 15 is sequentially transferred to the expansion chamber 36 through the precision orifice 4 of the first channel 63, the downward channel 52, the lateral channel 53, and the upward channel 54. When the fluid sample 3 flows through the precision orifice 4, the cells contained in the fluid sample 3 are subjected to a large shear stress, thereby promoting the crushing of the cells. Here, the top layer film 46 of the chip assembly 45 and the gasket 49 disposed on the upper surface side of the chip assembly 45 are formed with openings at positions overlapping the vent hole 48, and the vent hole 42C formed in the clamp surface 42A of the upper housing 42 is also disposed at a position overlapping the vent hole 48. Thereby, the expansion chamber 36 of the chip assembly 45 is vented through the vent hole 48 and the pressure relief portion 21 (vent channel 51, threaded barb connector 43, ID tube 44), and atmospheric pressure is introduced. Therefore, the fluid sample 3 transferred from the pressure chamber 15 to the expansion chamber 36 through the first channel 63 is depressurized in the expansion chamber 36. As a result, the cells contained in the fluid sample 3 rapidly expand, and the crushing of the cells can be further promoted. As described above, the fluid sample 3 after the cell crushing process is collected in the expansion chamber 36 of the chip assembly 45 (chip 32).

[0096] Of course, the upper housing 42 and the lower housing 50 in the present embodiment are detachable. After the operation (after use) of the ninth explosive cell disruption device D9, the upper housing 42 and the lower housing 50 are separated by removing the connecting pin 64 or the like, and the chip assembly 45 (chip 32) housed in the chip recess 50A of the lower housing 50 is exposed. Then, for example, the fluid sample 3 after the cell disruption treatment can be recovered from the expansion chamber 36 by removing, such as peeling off the topmost layer film 46 covering the upper surface of the chip 32. Also, in the present embodiment as well, as described in the seventh embodiment, a reagent may be added to the fluid sample 3 collected in the expansion chamber 36 and various reaction treatments may be performed.

[0097] <Tenth Embodiment> Figures 23 to 26 show an embodiment very similar to Figures 19 to 22. In this embodiment, the chip is replaced by a laser-cut plastic or glass chip having a precision orifice 4 formed in the chip shape. Thus, the chip is essentially an integrated part of the lower housing 50. This embodiment does not include designated ventilation, but ventilation occurs through the gap between the upper housing 42 and the lower housing 50.

[0098] FIG. 23 shows a cross-sectional view of a tenth explosive cell disruption device D10 according to the tenth embodiment. The tenth explosive cell disruption device D10 is a modified example of the ninth explosive cell disruption device D9. In the present embodiment, the same reference numerals are used for the same elements as in the embodiments described above. In the tenth explosive cell disruption device D10, the chip 32 is formed in a chip shape by processing the upper surface of the lower housing 50 by laser cutting technology or the like, and is realized in a mode in which the chip 32 is integrated with the lower housing 50. FIG. 24 is a plan view of a chip formation region on the upper surface of the lower housing 50 where the chip 32 is formed. The chip formation region in the lower housing 50 can be formed of, for example, a polymer material (such as plastic) or glass. FIGS. 25 and 26 are schematic cross-sectional views of the chip 32 (chip formation region in the lower housing 50) in the tenth explosive cell disruption device D10. FIG. 25 shows a first aspect before the combustion of the explosive attachment, and FIG. 26 shows a second aspect after the combustion of the explosive attachment.

[0099] The chip 32 formed by being integrated with the chip formation region of the lower housing 50 is provided with a pressure chamber 15 formed by the first recess 33 and capable of accommodating the fluid sample 3 before the cell disruption process, and an expansion chamber 36 formed by the second recess 35. The pressure chamber 15 and the expansion chamber 36 are connected via a first channel 63 including a precision orifice 4. Similar to the seventh embodiment, the expansion chamber 36 in the chip 32 has a sufficiently larger volume than the pressure chamber 15, and when the fluid sample 3 enters the expansion chamber 36 from the pressure chamber 15, the fluid sample 3 is depressurized, and the cells contained in the fluid sample 3 rapidly expand.

[0100] In the upper housing 42 of the tenth explosive cell crusher D10, an initiator 28 and a pressure relief channel 18 are provided as in the ninth embodiment, while a pressure relief portion 21 is not provided. Also, as in the ninth embodiment, holes for fitting pins for connection are provided in the upper housing 42 and the lower housing 50, respectively, and the upper housing 42 and the lower housing 50 can be integrally connected using the pins, and after the operation of the device, the upper housing 42 and the lower housing 50 can be separated from each other. Further, the upper surface of the chip 32 integrated with the lower housing 50 may be covered by the top layer film 46. In this case, small holes or weak portions for venting the combustion gas discharged from the gas outlet 42B of the clamp surface 42A in the upper housing 42 to the pressure chamber 15 may be formed in the top layer film 46. Also, when assembling the upper housing 42 to the lower housing 50, a gasket 49 may be interposed between the upper surface of the chip 32 integrated with the lower housing 50 and the clamp surface 42A in the upper housing 42. In this case, an opening may be formed in the gasket 49, and the combustion gas discharged from the gas outlet 42B of the clamp surface 42A may be supplied to the pressure chamber 15.

[0101] The operation of the tenth explosive cell disruption device D10 configured as described above is basically the same as that of the ninth explosive cell disruption device D9 according to Embodiment 9. That is, when the initiator 28 operates, the explosive charge 5 is ignited and burned, and the combustion gas is supplied to the pressure chamber 15 of the chip 32 through the pressure release channel 18, and the fluid sample 3 contained in the pressure chamber 15 is rapidly pressurized, thereby disrupting the cells contained in the fluid sample 3. Then, the fluid sample 3 pressurized in the pressure chamber 15 is transferred to the expansion chamber 36 through the first channel 63 including the precision orifice 4. When the fluid sample 3 flows through the precision orifice 4, the cells contained in the fluid sample 3 are subjected to a large shear stress, which promotes the disruption of the cells. When the fluid sample 3 flows from the first channel 63 into the expansion chamber 36 with a large volume, the cells contained in the fluid sample 3 rapidly expand due to decompression, further promoting cell disruption. In this way, the fluid sample 3 containing cells after the disruption process is collected in the expansion chamber 36. Note that, similar to the ninth embodiment, the chip 32 may be provided with a vent 48 communicating with the expansion chamber 36, and atmospheric pressure may be introduced into the expansion chamber 36 through the vent 48.

[0102] <Embodiment 11> Figs. 27 to 29 show schematic cross-sectional views of an explosive cell disruption device including a sample chip according to the eleventh embodiment. Fig. 28 schematically shows the chip in the first mode before pressurization, and Fig. 29 schematically shows the chip in the second mode after pressurization. This embodiment is the same as the embodiment shown in Figs. 13 to 15, but does not include the precision orifice 4. Therefore, this embodiment is based on the same concept of the hydrostatic shock pressure wave as the embodiment described with reference to Figs. 5 and 6. Elements similar to those described in Figs. 13 to 15 are denoted by the same reference numerals.

[0103] This 11th embodiment according to FIGS. 27 to 29 is essentially the concept of the 3rd embodiment according to FIGS. 5 and 6 in chip form. Only one recess 33 for holding the fluid sample 3 is shown, but it is also possible to mount on one single chip a chip having a plurality of recesses 33 for a plurality of different samples. A plurality of pyrotechnic charges 5 may be applied simultaneously on a plurality of sample chips, or a single pyrotechnic charge housing may be movable between a plurality of samples and the pyrotechnic charge housing may be reloaded while moving between samples.

[0104] The 11th pyrotechnic cell disruption device D11 shown in FIGS. 27 to 29 includes a chip 32 (pyrotechnic cell destruction chip) having a pressure chamber 15 formed by a first recess 33 formed in a substrate 34. Further, the 11th pyrotechnic cell disruption device D11 includes a pair of clamps 31 that clamp the chip 32 by being respectively disposed on the upper (top) and lower (bottom) portions of the chip 32 (pyrotechnic cell destruction chip), a pyrotechnic charge chamber housing 16 that forms a pyrotechnic charge chamber 11, a pyrotechnic charge 5 and the like housed in the pyrotechnic charge chamber 11, and the like. Also, the chip 32 has a thin top layer film 46 that covers the upper surface of the substrate 34, and the first recess 33 (pressure chamber 15) of the substrate 34 can be sealed from the outside by the top layer film 46. Note that FIG. 28 schematically shows a cross-sectional view and a plan view of the 11th pyrotechnic cell disruption device D11 before operation (before pressurization). In FIG. 28, the illustration of the clamp 31 is omitted, and a cross-sectional view is shown in the upper row and a plan view is shown in the lower row. Also, FIG. 29 schematically shows a cross-sectional view and a plan view of the 11th pyrotechnic cell disruption device D11 after operation (after pressurization). In FIG. 29, the illustration of the clamp 31 is omitted, and a cross-sectional view is shown in the upper row and a plan view is shown in the lower row. Note that in the plan views of FIGS. 28 and 29, the upper surface of the substrate 34 is shown through the top layer film 46.

[0105] When the eleventh explosive cell disruption device D11 configured as described above operates, the explosive charge 5 is ignited, and combustion gas is generated by the combustion of the explosive charge 5. As a result, the pressure inside the explosive charge chamber 11 increases, the fracture part 17 of the explosive charge chamber housing 16 ruptures, and the pressure release channel 18 communicates with the explosive charge chamber 11. Consequently, the pressure inside the explosive charge chamber 11 is released, the part of the topmost film 46 facing the pressure release channel 18 is torn, and the combustion gas flows into the pressure chamber 15 in the chip 32. Alternatively, a small hole may be formed in advance in the part of the topmost film 46 facing the pressure release channel 18, and the combustion gas may be supplied to the pressure chamber 15 through the small hole. The pressure chamber 15 supplied with the combustion gas of the explosive charge 5 is rapidly pressurized, and as a result, the cells contained in the fluid sample 3 accommodated in the pressure chamber 15 can be disrupted. Also, the eleventh explosive cell disruption device D11 may include the precision orifice 4 and the pressure release part 21 described in the above-described embodiment.

[0106] Regarding the above embodiments, the following additional remarks are shown. (Additional Remark 1) An explosive charge configured to be ignited and to burn upon ignition, and A pressure chamber configured to accommodate a fluid sample containing cells and to be pressurized upon ignition and combustion of the explosive charge, and An explosive cell disruption device comprising the same. (Additional Remark 2) Further comprising a pressure chamber outlet connecting the pressure chamber to the external space, and The pressure chamber outlet has an orifice that applies a shear stress to the fluid sample when the fluid sample is circulated, The explosive cell disruption device according to Additional Remark 1. (Additional Remark 3) The orifice is formed in a separate part adhered or press-fitted to the pressure chamber outlet, the explosive cell disruption device according to Additional Remark 2. (Additional Remark 4) The pyrotechnic charge is housed in a separate pyrotechnic charge chamber separated from the pressure chamber, and is the pyrotechnic cell crushing device according to any one of Appendices 1 to 3. (Appendix 5) The pyrotechnic cell crushing device according to Appendix 4, wherein the pyrotechnic charge chamber is formed in a pyrotechnic charge chamber housing having a breaking portion that breaks when the pyrotechnic charge is ignited and burned. (Appendix 6) The pyrotechnic cell crushing device according to Appendix 5, wherein the breaking portion is formed by a vulnerable portion where the portion of the pyrotechnic charge chamber housing facing the pressure chamber is more vulnerable than other portions. (Appendix 7) The pyrotechnic cell crushing device according to Appendix 6, wherein the vulnerable portion has a thinner member thickness of the pyrotechnic charge chamber housing than other portions. (Appendix 8) The pyrotechnic cell crushing device according to any one of Appendices 5 to 7, wherein the pyrotechnic charge chamber directly opens to the pressure chamber when the breaking portion breaks. (Appendix 9) A first cylinder chamber for housing the pyrotechnic charge, A first piston that is at least partially housed in the first cylinder chamber and is movable relative to the first cylinder chamber under the pressure generated by the ignition and combustion of the pyrotechnic charge, A second piston provided in the pressure chamber and connected to the first piston, further comprising When the pyrotechnic charge is ignited and burned, the second piston is interlocked with the first piston to pressurize the fluid sample housed in the pressure chamber. The pyrotechnic cell crushing device according to any one of Appendices 1 to 3. (Appendix 10) The pyrotechnic cell crushing device according to Appendix 9, wherein the first cylinder chamber is formed in a first cylinder chamber housing that is at least partially housed in the pressure chamber. (Appendix 11) The pressure chamber is further provided with a diaphragm that partitions the pressure chamber into a first internal space into which combustion gas of the pyrotechnic charge is introduced during ignition and combustion of the pyrotechnic charge, and a second internal space in which the fluid sample is accommodated. During ignition and combustion of the pyrotechnic charge, the combustion gas is introduced into the first internal space, causing the diaphragm to deform, and the volume of the second internal space decreases, thereby pressurizing the fluid sample accommodated in the second internal space. The pyrotechnic cell crushing device according to any one of Appendices 1 to 8. (Appendix 12) The pressure chamber further includes a pressure chamber outlet that connects the second internal space to the external space. The pressure chamber outlet has an orifice that applies a shear stress to the fluid sample when the fluid sample is circulated. The pyrotechnic cell crushing device according to Appendix 11. (Appendix 13) After the pressure chamber is pressurized by ignition and combustion of the pyrotechnic charge, the pressure chamber further includes a pressure release portion that releases the pressure from the pressure chamber. The pyrotechnic cell crushing device according to any one of Appendices 1 to 12. (Appendix 14) The pyrotechnic cell crushing device according to Appendix 13, wherein the pressure release portion has a valve body. (Appendix 15) The pyrotechnic cell crushing device according to Appendix 14, wherein the valve body is a pressure release valve that is opened under a predetermined pressure. (Appendix 16) The pyrotechnic cell crushing device according to Appendix 13, wherein the pressure release portion has a rupture plate that ruptures under a predetermined pressure. (Appendix 17) In the pressure chamber, a sample container filled with the fluid sample is accommodated. The pyrotechnic cell crushing device according to any one of Appendices 13 to 16. (Appendix 18) The pyrotechnic cell crushing device according to Appendix 17, wherein the sample container is a flexible pouch. (Appendix 19) The pressure chamber includes a pressure channel in which the pyrotechnic charge is disposed, and a sample container accommodation part that is coaxially connected to the pressure channel and accommodates the sample container, and is the pyrotechnic cell crushing device according to appended claim 17 or 18. (Appended claim 20) In the connection part of the sample container accommodation part to the pressure channel, a sample container placement part for placing the sample container is formed, and it is the pyrotechnic cell crushing device according to appended claim 19. (Appended claim 21) The cross-sectional area of the sample container accommodation part is larger than the cross-sectional area of the pressure channel, and the sample container placement part is formed by a step formed between the sample container accommodation part and the pressure channel, and it is the pyrotechnic cell crushing device according to appended claim 20. (Appended claim 22) A pressure vessel in which the pressure chamber is formed inside and the sample container accommodation part opens on the upper surface, A pressure release part is installed, and a cap that can be attached to the pressure vessel so as to cover the upper surface of the pressure vessel, and The pressure release part has a pressure release ventilation path that communicates the sample container accommodation part with the external space after the pressure chamber is pressurized by ignition and combustion of the pyrotechnic charge. The pyrotechnic cell crushing device according to any one of appended claims 19 to 21. (Appended claim 23) In a state where the cap is attached to the pressure vessel, the pressure channel, the sample container accommodation part, and the pressure release ventilation path are arranged coaxially, and it is the pyrotechnic cell crushing device according to appended claim 22. (Appended claim 24) The pressure release ventilation path is blocked by a rupture plate or a valve body, and the sample container accommodation part communicates with the external space when the rupture plate ruptures or the valve body is opened. The pyrotechnic cell crushing device according to appended claim 22 or 23. (Appended claim 25) The pressure chamber includes a pressurized space portion that extends in a first direction and has a proximal end and a distal end with respect to the pressure release portion, and a pressure channel that branches from the middle of the pressurized space portion in a second direction different from the first direction and is connected to the pressurized space portion. The pyrotechnic charge is disposed in the pressure channel. The pressurized space portion has a sample container accommodation portion for accommodating the sample container between a connection portion with the pressure channel and the distal end. The pyrotechnic cell crushing device according to appended note 17 or 18. (Appended note 26) The pyrotechnic cell crushing device according to appended note 25, wherein the first direction and the second direction are orthogonal to each other. (Appended note 27) A pressure vessel having a bottomed shape, with the pressure chamber formed inside, and the proximal end of the pressurized space portion opening on the upper surface. A cap that is installed with the pressure release portion and can be attached to the pressure vessel so as to cover the upper surface of the pressure vessel. Comprising. The pressurized space portion extends along the vertical direction of the pressure vessel, and the distal end is positioned at the bottom of the pressure vessel so that the sample container can be placed on the bottom. The pyrotechnic cell crushing device according to appended note 25 or 26. (Appended note 28) The pressure release portion has a pressure release ventilation path that communicates the pressurized space portion with the external space after the pressure chamber is pressurized by ignition and combustion of the pyrotechnic charge. The proximal end of the pressurized space portion is connected to the pressure release ventilation path. The pyrotechnic cell crushing device according to any one of appended notes 25 to 27. (Appended note 29) The pyrotechnic cell crushing device according to appended note 28, wherein the pressurized space portion and the pressure release ventilation path are coaxially arranged when the cap is attached to the pressure vessel. (Appended note 30) The pressure relief ventilation path is blocked by a rupture plate or a valve body, and the sample container housing portion communicates with the external space when the rupture plate ruptures or the valve body is opened. The explosive cell crushing device according to appended note 28 or 29. (Appended note 31) Comprising a chip having a substrate, The pressure chamber is formed by a first recess provided on the surface of the substrate. The explosive cell crushing device according to appended note 1. (Appended note 32) Comprising a film covering the surface of the substrate, The explosive cell crushing device according to appended note 31, wherein the pressure chamber is sealed by covering the first recess with the film. (Appended note 33) Further comprising an explosive charge chamber housing for housing the explosive charge, The explosive charge chamber housing is disposed above the pressure chamber. The explosive cell crushing device according to appended note 31. (Appended note 34) The explosive charge chamber housing has a breaking portion that breaks during ignition and combustion of the explosive charge, The breaking portion is disposed so as to face the pressure chamber. The explosive cell crushing device according to appended note 33. (Appended note 35) An expansion chamber formed by a second recess provided on the surface of the substrate, A first channel provided on the substrate and connecting the pressure chamber and the expansion chamber, And further comprising, The first channel has an orifice that applies a shear stress to the fluid sample when the fluid sample is circulated. The explosive cell crushing device according to any one of appended notes 31 to 34. (Appended note 36) The expansion chamber has a larger volume than the pressure chamber, and the fluid sample is depressurized when flowing from the pressure chamber through the orifice into the expansion chamber. The pyrotechnic cell disruption device according to Supplementary Note 35. (Supplementary Note 37) The pyrotechnic cell disruption device according to Supplementary Note 35 or 36, wherein the expansion chamber is open to the outside. (Supplementary Note 38) A reaction chamber formed by a third recess provided on the surface of the substrate and containing a reagent for reacting with cells contained in the fluid sample. A second channel provided on the substrate and connecting the expansion chamber and the reaction chamber. The pyrotechnic cell disruption device according to any one of Supplementary Notes 35 to 37, further comprising the above. (Supplementary Note 39) The pyrotechnic cell disruption device according to Supplementary Note 38, wherein the reaction chamber is open to the outside. (Supplementary Note 40) A detection chamber formed by a fourth recess provided on the surface of the substrate. A third channel provided on the substrate and connecting the reaction chamber and the detection chamber. The pyrotechnic cell disruption device according to Supplementary Note 38 or 39, further comprising the above. (Supplementary Note 41) The pyrotechnic cell disruption device according to any one of Supplementary Notes 31 to 40, further comprising a pair of clamps for clamping the chip. (Supplementary Note 42) The pair of clamps includes an upper clamp having a substantially flat clamp surface facing the loading area of the chip and a lower clamp having a chip recess configured to accommodate the chip. The pyrotechnic cell disruption device according to Supplementary Note 41. (Supplementary Note 43) The pyrotechnic cell disruption device according to Supplementary Note 42, wherein the upper clamp and the lower clamp each have a housing form. (Supplementary Note 44) accommodating a fluid sample containing cells in a pressure chamber configured to be pressurized by an explosive charge; pressurizing the fluid sample accommodated in the pressure chamber by igniting and burning the explosive charge; An explosive cell disruption method comprising: (Appendix 45) The explosive cell disruption method according to Appendix 44, further comprising holding the pressure in the pressure chamber generated from the combustion of the explosive charge for a certain period. (Appendix 46) The explosive cell disruption method according to Appendix 44 or 45, further comprising discharging the fluid sample pressurized in the pressure chamber to an external space through an orifice, and applying a shear force generated when passing through the orifice to the fluid sample. (Appendix 47) The explosive cell disruption method according to Appendix 46, wherein the external space is an expansion chamber that receives the fluid sample that has passed through the orifice, and the fluid sample is expanded when received in the expansion chamber. (Appendix 48) The explosive cell disruption method according to Appendix 47, further comprising adding a reagent to the fluid sample in the expansion chamber and reacting the fluid sample with the reagent. (Appendix 49) The explosive cell disruption method according to Appendix 47, further comprising moving the fluid sample from the expansion chamber into a reaction chamber containing a reagent, and reacting the fluid sample with the reagent in the reaction chamber. (Appendix 50) The explosive cell disruption method according to Appendix 49, further comprising discharging the fluid sample from the reaction chamber into a detection chamber after reacting the fluid sample with the reagent in the reaction chamber. (Appendix 51) The explosive cell disruption method according to any one of Appendices 48 to 50, wherein the reaction by the reagent is a polymerase chain reaction (PCR) or a loop-mediated isothermal amplification (LAMP). (Appendix 52) The pyrotechnic cell disruption method according to any one of Appendices 44 to 51, which does not include lysing the cells contained in the fluid sample using a chemical substance.

[0107] Each aspect disclosed in this specification can be combined with any other feature disclosed in this specification.

Explanation of Signs

[0108] D1~D11 ··· Pyrotechnic cell disruption device 1 ··· Cylinder body 2 ··· Piston 3 ··· Sample 4 ··· Precision orifice 5 ··· Pyrotechnic charge 6 ··· Cap 7 ··· Low-pressure space 8 ··· High-pressure space 11 ··· Pyrotechnic charge chamber 14 ··· Diaphragm 15 ··· Pressure chamber 16 ··· Pyrotechnic charge chamber housing 20 ··· Pressure relief valve 28 ··· Initiator 31 ··· Clamp 32 ··· Chip 33 ··· First recess 34 ··· Substrate 35 ··· Second recess 36 ··· Expansion chamber 37 ··· Reaction chamber 38 ··· Reagent 41 ··· Detection chamber

Claims

1. An explosive charge configured to be ignited and burn upon ignition, a pressure chamber configured to contain a fluid sample containing cells and to be pressurized upon ignition and combustion of the explosive charge, a pressure chamber outlet connecting the pressure chamber to an external space, comprising: the pressure chamber outlet has an orifice that applies a shear stress to the fluid sample when the fluid sample is circulated, the explosive charge, the pressure chamber, and the orifice are arranged in a straight line in this order, an explosive cell disruption device.

2. The explosive charge is housed in a separate explosive charge chamber separated from the pressure chamber, the explosive charge chamber is formed within an explosive charge chamber housing having a breakage portion that ruptures upon ignition and combustion of the explosive charge, and directly opens to the pressure chamber when the breakage portion breaks, The explosive cell disruption device according to Claim 1.

3. a first cylinder chamber that houses the explosive charge, a first piston that is at least partially housed in the first cylinder chamber and is movable relative to the first cylinder chamber under the pressure generated by ignition and combustion of the explosive charge, a second piston provided in the pressure chamber and connected to the first piston, further comprising: when the explosive charge is ignited and burned, the second piston interlocks with the first piston to pressurize the fluid sample contained in the pressure chamber, The explosive cell disruption device according to Claim 1.

4. further comprising a diaphragm that divides the pressure chamber into a first internal space into which combustion gas of the explosive charge is introduced upon ignition and combustion of the explosive charge and a second internal space in which the fluid sample is contained, when the combustion gas is introduced into the first internal space upon ignition and combustion of the explosive charge, the diaphragm deforms, and the volume of the second internal space decreases, thereby pressurizing the second internal space, The explosive cell disruption device according to Claim 1 or 2. ​

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