Summary of the invention
Based on this, it is necessary to which for above-mentioned manually progress paramagnetic particle method nucleic acid extraction, consuming time is long, nucleic acid extraction effectThe low problem of rate provides a kind of nucleic acid extraction instrument being simple and efficient.
Specific technical solution is as follows:
A kind of nucleic acid extraction instrument extracts nucleic acid using the reaction plate with several reacting holes, and nucleic acid extraction instrument includes:
Heating vibration device, reaction plate described in mountable and heating vibration, makes the part of the reaction plate reacting holeReach the first preset temperature, the part reacting hole in other described reacting holes reaches the second preset temperature；
Temperature control reagent device has refrigeration mechanism, for maintaining the article being placed on the temperature control reagent deviceThird preset temperature；
Magnetic bead evenly mixing device has movement mechanism, for mixing the suspension containing magnetic beads being placed on the magnetic bead evenly mixing device；
Magnetic bead transfer device, has a moveable magnetic bar magnet, and the adsorbable magnetic bead of bar magnet is with by the magnetic beadIt is transferred to predeterminated position.
Above-mentioned nucleic acid extraction instrument is in use, sample and reagent are placed on temperature control reagent device to maintain low temperature shapeState, suspension containing magnetic beads are placed in keep magnetic bead even suspension on magnetic bead evenly mixing device, and reaction plate is placed in heating vibration deviceOn, so that part reacting hole is reached the required cracking temperature of cracking, elution needed for a part in other reacting holes reaches elutionTemperature, the reacting hole of remaining room temperature are then used to wash.It first places a sample into the reacting hole for reaching cracking temperature, cracking is addedLiquid, in conjunction with liquid and magnetic bead, lysate can damage cells structure in conjunction with liquid, make the abundant separate out of nucleic acid, with the magnetic bead in solutionIn conjunction with then magnetic bead and the nucleic acid absorption in conjunction with magnetic bead are transferred in the reacting hole of room temperature and are passed through by magnetic bead transfer deviceCleaning solution washing is added and removes residual impurity.Then magnetic bead and nucleic acid are transferred in the reacting hole for reaching eluting temperature again, are led toThe nucleic acid that eluent Dissociative is added on magnetic bead is crossed, finally moves away magnetic bead, in above each step, is shaken by heatingDynamic device dynamic respons plate makes cracking washing elution sufficiently, and the nucleic acid of high concentration and high-purity then stays in reacting hole.By thisNucleic acid extraction instrument eliminates the operation for manually carrying out paramagnetic particle method nucleic acid extraction, and stability is good, and nucleic acid extraction efficiency is significantlyIt improves, and the device structure is simple, it is at low cost, it has a good application prospect.
The magnetic bead transfer device includes: in one of the embodiments,
Substrate, the substrate are equipped with substrate actuator；
Magnetosheath frame, is installed on the substrate, and the magnetosheath frame is equipped with hollow and open at one end magnetosheath；
Bar magnet mechanism, the bar magnet mechanism are equipped with the bar magnet, and the bar magnet mechanism is installed on the substrate and can beThe relatively described magnetosheath frame moves back and forth under the driving of the substrate actuator, to drive the relatively described magnetosheath frame of the bar magnet reciprocalIt moves and protrudes into or far from the magnetosheath；
Mobile mechanism, has moveable moving arm, and the moving arm is connect to drive the substrate to move with the substrateIt is dynamic.
The substrate is equipped with guide rail slide block in one of the embodiments, and the guide rail slide block is described including being fixed onThe guide rail of substrate and the sliding block that can be slided along the guide rail, the bar magnet mechanism are connected with the slide block to be installed on the basePlate, the substrate actuator are connect to drive the bar magnet mechanism to move back and forth along the guide rail with the bar magnet mechanism.
The bar magnet mechanism includes connecting plate and bar magnet frame in one of the embodiments, the one end of the connection board and instituteSliding block connection is stated, the other end far from the sliding block is connect with the bar magnet frame, and the bar magnet is set to the bar magnet frame.
The substrate actuator is equipped with substrate drive shaft in one of the embodiments, and the substrate actuator passes throughThe substrate drive shaft is threadedly coupled with the connecting plate, and the substrate actuator can drive the substrate drive shaft rotation with bandThe connecting plate is moved to move back and forth along the guide rail.
Reciprocating liquid relief sliding block is additionally provided on the moving arm in one of the embodiments, the liquid relief is slidingBlock is equipped with liquid relief part far from one end of the moving arm and is used for transfer liquid.
The heating vibration device includes: in one of the embodiments,
Heating mechanism, it is mountable and heat the reaction plate, including the first heating component and the second heating component, describedThe part reacting hole that one heating component is used to heat the reaction plate reaches first preset temperature；Second heatingThe part reacting hole that component is used to heat in other described reacting holes reaches second preset temperature；
Vibrating mechanism is connect with the heating mechanism, for driving the heating mechanism vibration to drive the reaction plateVibration.
First heating component includes the first supporting element and the first heating member in one of the embodiments, and described theTwo heating components include the second supporting element and the second heating member, and first supporting element and second supporting element cooperatively form peaceThe installation position of the reaction plate is filled, first heating member is connect with first supporting element will to pass through first supporting elementFor heat transfer to the reaction plate, second heating member is connect with second supporting element will to pass through second supporting elementHeat transfer is to the reaction plate.
First heating component is equipped with the communicated to connect with first heating member in one of the embodiments,One temperature sense part to detect the temperature of the reacting hole of the first heating component heating, and controls first heatingPart stops or operation；Second heating component is equipped with the second temperature induction pieces communicated to connect with second heating member,To detect the temperature of the reacting hole of the second heating component heating, and controls second heating member and stop or run.
The vibrating mechanism includes driving assembly and rotary components in one of the embodiments, the rotary components withHeating mechanism connection, the driving component connect with the rotary components to drive the rotary components to be eccentrically rotated thusThe heating mechanism is driven to rotate and vibrate.
Specific embodiment
To facilitate the understanding of the present invention, a more comprehensive description of the invention is given in the following sections with reference to the relevant attached drawings.In attached drawingGive presently preferred embodiments of the present invention.But the invention can be realized in many different forms, however it is not limited to this paper instituteThe embodiment of description.On the contrary, purpose of providing these embodiments is keeps the understanding to the disclosure more thoroughComprehensively.
It should be noted that it can directly on the other element when element is referred to as " being installed on " another elementOr there may also be elements placed in the middle.When an element is considered as " connection " another element, it can be direct connectionTo another element or it may be simultaneously present centering elements.When an element is considered as " connection " another element, it canTo be directly to another element or may be simultaneously present centering elements.
Unless otherwise defined, all technical and scientific terms used herein and belong to technical field of the inventionThe normally understood meaning of technical staff is identical.Term as used herein in the specification of the present invention is intended merely to description toolThe purpose of the embodiment of body, it is not intended that in the limitation present invention.Term as used herein "and/or" includes one or more phasesAny and all combinations of the listed item of pass.
As shown in Figure 1, a kind of nucleic acid extraction instrument 600 of a preferred embodiment of the present invention, using with several reacting holesReaction plate 200 extract nucleic acid, nucleic acid extraction instrument 600 include heating vibration device 100, magnetic bead transfer device 300, temperature control examinationAgent device 400 and magnetic bead evenly mixing device 500.
Heating vibration device 100 is mountable and heating vibration reaction plate 200, reaches the part reacting hole of reaction plate 200First preset temperature, the part reacting hole in other reacting holes reach the second preset temperature.Temperature control reagent device 400 has refrigerationMechanism, for making the article being placed on temperature control reagent device 400 maintain third preset temperature.Magnetic bead evenly mixing device 500 hasThere is movement mechanism, for mixing the suspension containing magnetic beads being placed on magnetic bead evenly mixing device.Magnetic bead transfer device 300 has moveableMagnetic bar magnet 331, the adsorbable magnetic bead of bar magnet 331 is to be transferred to predeterminated position for magnetic bead.
The nucleic acid extraction instrument 600 of the present embodiment in use, by sample and reagent be placed on temperature control reagent device 400 withLow-temperature condition is maintained, suspension containing magnetic beads are placed in keep magnetic bead even suspension on magnetic bead evenly mixing device 500, by reaction plate 200It is installed on heating vibration device 100, cracking temperature needed for making part reacting hole reach cracking, one in other reacting holesDivide eluting temperature needed for then reaching elution, the reacting hole of remaining room temperature is then used to wash.It first places a sample into and reaches cracking temperatureIn the reacting hole of degree, lysate is added, in conjunction with liquid, lysate can damage cells structure in conjunction with liquid, and nucleic acid is made sufficiently to dissociateCome, the nucleic acid to dissociate after suspension containing magnetic beads be added with the magnetic bead in solution ining conjunction with, then pass through magnetic bead transfer device 300 by magnetic bead andNucleic acid absorption in conjunction with magnetic bead, which is transferred in the reacting hole of room temperature, removes residual impurity by the way that cleaning solution washing is added.Then againMagnetic bead and nucleic acid are transferred in the reacting hole for reaching eluting temperature, by the way that core of the eluent Dissociative on magnetic bead is addedAcid finally moves away magnetic bead, in above each step, washs cracking by 100 dynamic respons plate 200 of heating vibration deviceSufficiently, the nucleic acid of high concentration and high-purity then stays in reacting hole for elution.By the nucleic acid extraction instrument 600, eliminate artificialThe operation of paramagnetic particle method nucleic acid extraction is carried out manually, stability is good, and nucleic acid extraction efficiency greatly improves, and the device structure is simple,It is at low cost, it has a good application prospect.
Further, as shown in Figures 2 and 3, magnetic bead transfer device 300 includes substrate 310, magnetosheath frame 320, bar magnet mechanism330 and mobile mechanism's (not shown).Substrate 310 is equipped with substrate actuator 311, and magnetosheath frame 320 is installed on substrate 310, magnetosheathFrame 320 is equipped with hollow and open at one end magnetosheath 321.Bar magnet mechanism 330, which is equipped with, has magnetic bar magnet 331, bar magnet machineStructure 330 is installed on substrate 310 and opposite magnetosheath frame 320 can move back and forth under the driving of substrate actuator 311 to drive bar magnet331 opposite magnetosheath framves 320 move back and forth, so that bar magnet 331 be made to protrude into or far from magnetosheath 321.Mobile mechanism has moveableMoving arm 341, moving arm 341 are connect to drive substrate 310 mobile with substrate 310.Specifically in the present embodiment, moving arm 341Substrate 310 can be driven to move along the axial direction or radial direction of bar magnet 331, it will be understood that move mode is without being limited thereto, can rootIt is adjusted according to the transfer needs of magnetic bead.
In this way, can first place a sample into the reacting hole of reaction plate 200, eucaryotic cell structure is destroyed by lysate, in conjunction with liquid,Make the abundant separate out of nucleic acid, in conjunction with the magnetic bead in solution, substrate 310 is then driven by the moving arm 341 of mobile mechanismMovement protrudes into magnetosheath 321 in reacting hole, then drives the movement of bar magnet mechanism 330 to protrude into bar magnet 331 by substrate actuator 311In magnetosheath 321, magnetic bead and the nucleic acid in conjunction with magnetic bead are then adsorbed on magnetosheath 321.Then moving substrate 310 stretches magnetosheath 321Enter into the reacting hole for washing, drives the movement of bar magnet mechanism 330 to make bar magnet 331 far from magnetosheath by substrate actuator 311321, dynamic respons plate 200 is dispersed in magnetic bead and nucleic acid disengaging magnetosheath 321 in cleaning solution, and is sufficiently washed and removed by cleaning solutionRemove residual impurity.Then substrate actuator 311 drives the movement of bar magnet mechanism 330 that bar magnet 331 is made to protrude into magnetosheath 321 again and adsorbs magneticPearl and nucleic acid, then moving substrate 310 protrudes into magnetosheath 321 in the reacting hole for being used for eluting, and is existed by eluent DissociativeNucleic acid on magnetic bead, last moving substrate 310 move away the magnetic bead that elution finishes, and the nucleic acid of high concentration and high-purity then stays inIn reacting hole, magnetic bead transfer efficiency is high, and stability is good, is remarkably improved nucleic acid extraction efficiency and quality.
Specifically, substrate 310 is equipped with guide rail slide block 312, and guide rail slide block 312 includes the guide rail for being fixed on substrate 3103121 and the sliding block 3122 that can slide along guide rail 3121, bar magnet mechanism 330 connect to be installed on substrate 310, base with sliding block 3122Plate actuator 311 is connect to drive bar magnet mechanism 330 to move back and forth along guide rail 3121 with bar magnet mechanism 330.In the present embodiment,Substrate actuator 311 is linear stepping motor, is fixed on substrate 310 by substrate actuator support frame 3111.
Bar magnet mechanism 330 includes connecting plate 332 and bar magnet frame 333, and 332 one end of connecting plate is connect with sliding block 3122, separateThe other end of sliding block 3122 is connect with bar magnet frame 333, and bar magnet 331 is set to bar magnet frame 333.
Further, substrate actuator 311 is equipped with substrate drive shaft 3112, and substrate actuator 311 is driven by substrateAxis 3112 is threadedly coupled with connecting plate 332, substrate actuator 311 the substrate drive shaft 311 can be driven to rotate in different directions withConnecting plate 332 is driven to move back and forth along guide rail 3121.
Preferably, bar magnet frame 333 is equipped with magnetic part mounting groove 3331, is equipped with magnetic part in magnetic part mounting groove 33313332, bar magnet 331 is contacted with magnetic part 3332, to enhance the magnetism of bar magnet 331 by magnetic part 3332, makes magnetic bead adsorption energyPower is more preferable.
Preferably, bar magnet mechanism 330 is equipped with bar magnet location sensitive plate 334, and substrate 310 is equipped with and substrate actuatorThe first position induction pieces 313 and second position induction pieces 314 of 311 communication connections, bar magnet mechanism 330 move back and forth pre-determined distanceWhen, bar magnet location sensitive plate 334 is corresponding with first position induction pieces 313 or 314 position of second position induction pieces, so that firstIt sets induction pieces 313 or induction pieces 314 control base board actuator 311 in the second position stops, back and forth being transported to limit bar magnet mechanism 330Dynamic distance makes the relative distance of bar magnet 331 and magnetosheath 321 control more stable and accurate.In the present embodiment, substrate 310On be fixed with circuit board 315, first position induction pieces 313 and second position induction pieces 314 are optocoupler, be installed on circuit board 315,With inductive slot, the reciprocating motion of bar magnet mechanism 330 can be such that bar magnet location sensitive plate 334 protrudes into corresponding inductive slot, to make theOne location sensitive part 313 or 314 control base board actuator 311 of second position induction pieces stop, and bar magnet mechanism 330 is prevented to continue originalThe movement in direction.
Preferably, 3331 both ends of magnetic part mounting groove are equipped with magnetic part fixed plate 3333, magnetic part fixed plate 3333 and magneticProperty part 3332 abut magnetic part 3332 to be fixed in magnetic part mounting groove 3331, to keep the stabilization of magnetic part 3332.
Preferably, referring to Fig. 1, being additionally provided with reciprocating liquid relief sliding block 351, liquid relief sliding block 351 on moving arm 341One end far from moving arm 341 is equipped with liquid relief part 352 and is used for transfer liquid, in this way, can pass through moving arm 341 and liquid relief sliding block351 mobile liquid relief parts 352, sample, reaction reagent and suspension containing magnetic beads are transferred in corresponding reacting hole, are further save artificialOperation improves extraction efficiency.
In the present embodiment, the quantity of bar magnet 331 is 12, and 12 magnetosheaths 321 and bar magnet 331 correspond, bar magnet 331It is arranged in a linear, corresponding with the reacting hole of 96 orifice plates, the quantity of liquid relief part 352 is 6, is arranged in a linear, with temperature control reagentReagent and sample position on device 400 is corresponding.It is appreciated that the quantity and arrangement mode of bar magnet 331 and liquid relief part 352 can be withAdjustment as needed, to adapt to different reaction plate 200 and demand.
Further, the diameter of magnetosheath 321 is 2mm-10mm, and the sample volume minimum for extraction is up to 20uL, energyEnough save sample and cost.
Specifically, as shown in figure 4, heating vibration device 100 includes heating mechanism 110 and vibrating mechanism 120.Heating mechanism110 is mountable and heat reaction plate 200, and heating mechanism 110 includes the first heating component 111 and the second heating component 112, and firstThe part reacting hole that heating component 111 is used to heat reaction plate 200 reaches the first preset temperature, and the second heating component 112 is used forThe part reacting hole heated in other reacting holes of reaction plate 200 reaches the second preset temperature.Vibrating mechanism 120 and heating mechanism110 connections, for driving the vibration of heating mechanism 110 to drive reaction plate 200 to vibrate.
In this way, only reaction plate 200 need to be placed in heating mechanism 110, the first heating component 111 will be on reaction plate 200Cracking temperature needed for reacting hole heating in part reaches cracking, the second heating component 112 is then by a part in other reacting holesEluting temperature needed for heating reaches elution, the reacting hole of remaining room temperature are then used to wash.Sample, which is first placed in, reaches cracking temperatureReacting hole in, destroy eucaryotic cell structure by lysate, in conjunction with liquid, make the abundant separate out of nucleic acid, thus in conjunction with magnetic bead, soAfterwards magnetic bead is transferred in the reacting hole of room temperature to wash by cleaning solution and removes residual impurity, then is transferred to reach magnetic bead and washIt in the reacting hole of de- temperature, is moved away by nucleic acid of the eluent Dissociative on magnetic bead, then by magnetic bead, in above each stepIn, heating mechanism 110 is driven to vibrate for vibrating mechanism 120 so that cracking washing elutes sufficiently, and the nucleic acid of high concentration and high-purity is thenStay in reacting hole, eliminate and be first heated to cracking temperature, be then cooled to room temperature, be again heated to eluting temperature it is very long whenBetween, magnetic bead transfer distance is short, is not necessarily to manual dynamic respons plate 200, substantially increases nucleic acid extraction efficiency and quality.
Specifically, the first heating component 111 includes the first supporting element 1111 and the first heating member 1112, the second heating component112 include the second supporting element 1121 and the second heating member 1122, and the first supporting element 1111 and the second supporting element 1121 cooperatively formThe installation position of reaction plate 200 is installed, the first heating member 1112 is connect through the first supporting element 1111 with the first supporting element 1111Reaction plate 200 is transferred heat to, the second heating member 1122 is connect through the second supporting element 1121 with the second supporting element 1121Transfer heat to reaction plate 200.
In the present embodiment, reaction plate 200 is 96 rectangular orifice plates, and the first supporting element 1111 and the second supporting element 1121 areFor the support frame with rectangular mounting groove, common cooperation is to form the installation position for installing reaction plate 200,1111 He of the first supporting elementSecond supporting element 1121 is contacted with the opposite end of reaction plate 200 respectively, so that it is opposite that heat is transferred to reaction plate 200 respectivelyFour row's reacting holes at both ends, intermediate four row's reacting holes are then room temperature.It is appreciated that the type of reaction plate 200 is without being limited thereto, such asVarious different materials and the structures such as 384 orifice plates, 108 orifice plates, tissue culture plate, PCR plate, the first supporting element 1111 and secondThe shape of supporting element 1121 can be according to the Adjusting Shape of reaction plate 200.Preferably, the first heating member 1112 and the second heating member1122 surfaces are coated with thermally conductive grease, improve heat transfer efficiency.
Further, the first heating component 111 is equipped with the first temperature sense communicated to connect with the first heating member 1112Part 1113 to detect the temperature of the reacting hole of the first heating component 111 heating, and controls the first heating member 1112 and stops or transportRow.Second heating component 112 is equipped with the second temperature induction pieces 1123 that communicate to connect with the second heating member 1122, to detect theThe temperature of the reacting hole of two heating components 112 heating, and control the second heating member 1122 and stop or run.Add in this way, working as firstThe reacting hole temperature that hot component 111 heats reaches the first preset temperature such as cracking temperature, and the first temperature sense part 1113 is transmittableSignal controls the first heating member 1112 and stops heating, otherwise continues to heat；When the reacting hole temperature of the second heating component 112 heatingReach the second preset temperature such as eluting temperature, second temperature induction pieces 1123 can be transmitted signal and control the stopping of the second heating member 1122Heating, otherwise continues to heat, so that corresponding reacting hole be made to maintain corresponding temperature.
Specifically, vibrating mechanism 120 includes driving assembly 121 and rotary components 122, rotary components 122 and heating mechanism110 connections, driving assembly 121 are connect to drive rotary components 122 to be eccentrically rotated to drive heating mechanism with rotary components 122110 rotations and vibration.
Further, driving assembly 121 includes rotation drive shaft 1211 and the rotation for driving the rotation drive shaft 1211 rotationTurn actuator 1212, rotary components 122 include support plate 1221 and coupling spindle 1222, and heating mechanism 110 is installed on support plate1221,1222 one end of coupling spindle is connect with support plate 1221, and the other end is connect with rotation drive shaft 1211, and coupling spindle 1222 turnsDynamic center deviation is in the center of rotation of rotation drive shaft 1211.More specifically, coupling spindle 1222 by set screw and D type hole withDrive shaft 1211 is rotated to connect, on coupling spindle 1222 from close to 1212 one end of rotary drive be successively arranged with lower bearing 1223,Sleeve 1224 and upper bearing (metal) 1225 are arranged with rotary shaft 1226, rotary shaft on lower bearing 1223, sleeve 1224 and upper bearing (metal) 1225Swivel mount 1227 is arranged on 1226, swivel mount 1227 is rotated by D type hole with rotary shaft 1226 together, and swivel mount 1227 is separateOne end of rotary shaft 1226 is connect with support plate 1221 far from the side of heating mechanism 110, in this way, drive shaft 1211 will be rotatedRotary drive drives heating mechanism 110 to rotate to support plate 1221.
Preferably, it is equipped with heat insulating mattress 1228 between heating mechanism 110 and support plate 1221, thus prevents heating mechanism110 heat transfer improves heating efficiency to support plate 1221.
Further, fixed plate 1213 is connected on rotary drive 1212, fixed plate 1213 is equipped with drives with rotationInductive signal can be transmitted to control in the coupling spindle location sensitive part 1214 that moving part 1212 communicates to connect, coupling spindle location sensitive part 1214Rotary drive 1212 processed stops, and coupling spindle 1222 is equipped with coupling spindle tablet corresponding with coupling spindle location sensitive part 12141215 so that coupling spindle location sensitive part 1214 generates inductive signal.In the present embodiment, coupling spindle location sensitive part 1214 hasThere is inductive slot, coupling spindle tablet 1215 includes to the extension 12151 and and extension extended far from 1222 direction of coupling spindle12151 occlusion parts 12152 to form an angle, after the rotation of coupling spindle 1222 drives coupling spindle tablet 1215 to rotate by a certain angleOcclusion part 12152 can be made to protrude into inductive slot, so that coupling spindle location sensitive part 1214 be made to generate actuated signal control rotation drivingPart 1212 stops.In this way, when needing to stop vibrating mechanism 120 coupling spindle location sensitive part 1214 only need to be started, to occlusion part12152 protrude into inductive slot, and can stop rotating actuator 1212.
Preferably, fixed plate 1213 is equipped with damping shock absorption part (not shown), to prevent support plate in the process of runningThe 1221 excessive liquid caused in reaction plate 200 of the inclined angle of vibration splash out.Specifically, damping shock absorption part is several to supportThe flexible column such as rubber column, plastic column etc. that plate 1221 extends, or it is surround the damping washer such as rubber washer etc. of coupling spindle 1222,Structure is without being limited thereto.
Preferably, rotary drive 1212 is equipped with damping and silencing pad 1216, fixed plate 1213 and damping and silencing pad 1216Connection by damping and silencing pad 1216 with rotary drive 1212 to be connect, so as to weaken the vibration and sending of fixed plate 1213Sound.
Preferably, coupling spindle 1222 is eccentric shaft, therefore partial center rotation can occur when rotation, can not only transmit rotation,Revolution can also be transmitted simultaneously, to make 110 whirling vibration of heating mechanism, improves mixed effect.
The nucleic acid extraction instrument 600 of the present embodiment passes through heating vibration device 100, magnetic bead transfer device 300, temperature control reagentThe cooperation of device 400 and magnetic bead evenly mixing device 500 eliminates the operation for manually carrying out paramagnetic particle method nucleic acid extraction, stabilityGood, nucleic acid extraction efficiency greatly improves, and the device structure is simple, at low cost, has a good application prospect.
Each technical characteristic of embodiment described above can be combined arbitrarily, for simplicity of description, not to above-mentioned realityIt applies all possible combination of each technical characteristic in example to be all described, as long as however, the combination of these technical characteristics is not depositedIn contradiction, all should be considered as described in this specification.
The embodiments described above only express several embodiments of the present invention, and the description thereof is more specific and detailed, but simultaneouslyIt cannot therefore be construed as limiting the scope of the patent.It should be pointed out that coming for those of ordinary skill in the artIt says, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to protection of the inventionRange.Therefore, the scope of protection of the patent of the invention shall be subject to the appended claims.