WO2019011088A1 - Nucleic acid purifier - Google Patents

Nucleic acid purifier Download PDF

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Publication number
WO2019011088A1
WO2019011088A1 PCT/CN2018/090554 CN2018090554W WO2019011088A1 WO 2019011088 A1 WO2019011088 A1 WO 2019011088A1 CN 2018090554 W CN2018090554 W CN 2018090554W WO 2019011088 A1 WO2019011088 A1 WO 2019011088A1
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WO
WIPO (PCT)
Prior art keywords
bracket
lifting
stirring
nucleic acid
stirring sleeve
Prior art date
Application number
PCT/CN2018/090554
Other languages
French (fr)
Chinese (zh)
Inventor
高爽
Original Assignee
上海奇法生物仪器有限公司
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Application filed by 上海奇法生物仪器有限公司 filed Critical 上海奇法生物仪器有限公司
Publication of WO2019011088A1 publication Critical patent/WO2019011088A1/en

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/10Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1003Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor
    • C12N15/1006Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor by means of a solid support carrier, e.g. particles, polymers
    • C12N15/1013Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor by means of a solid support carrier, e.g. particles, polymers by using magnetic beads

Definitions

  • the invention relates to the field of biological instruments, in particular to a nucleic acid purification automatic device based on nano magnetic beads.
  • Nucleic acids are widely found in animals and plants. In clinical diagnosis and treatment, or forensic identification, or genetic screening and recombination, people need to extract nucleic acids from samples (blood, saliva or other tissues), and the process of extracting nucleic acids is also called nucleic acid purification. The effect of nucleic acid purification directly affects the progress and results of research and diagnosis, so nucleic acid purification technology is an important technology in biotechnology.
  • a commonly used nucleic acid purification method is a magnetic rod method.
  • the magnetic rod method uses a magnetic rod to adsorb nano magnetic beads, and the nano magnetic beads adsorb nucleic acids to separate nucleic acids from the sample.
  • the working principle of the magnetic bar method is as shown in FIG. 1.
  • the magnetic bar 20, the stirring sleeve 21 and the deep hole plate 22 are arranged in order from top to bottom; wherein the deep hole plate 22 has a set of deep holes, and the deep holes include cracking.
  • the liquid hole 221, the magnetic bead hole 222, the washing liquid hole 223 (a plurality of washing liquid holes may be provided), and the eluent liquid hole 224 respectively store the corresponding reagents.
  • the specific steps of the nucleic acid purification process are: dropping the sample into the lysate to cleave the nucleic acid--collecting the magnetic beads to the lysate well--the magnetic beads are combined with the nucleic acid--collecting the magnetic beads to the washing holes (multiple washings)- The magnetic beads are collected to the elution well--the magnetic beads are recovered after elution, and finally the nucleic acid remains in the eluate.
  • the nucleic acid purifier is required to realize the basic actions as shown in FIG.
  • Chinese invention patent CN103897987B discloses an automatic nucleic acid extraction device based on nano magnetic beads.
  • the nucleic acid extraction device is mainly composed of a base and three mechanisms mounted on the base.
  • the three mechanisms are: a magnetic bar lifting mechanism, a stirring sleeve driving mechanism and a deep hole plate translation mechanism.
  • the three mechanisms are composed of a stepping motor, a screw nut mechanism, and a sliding bar that supports and guides.
  • the actions achieved by the above three mechanisms are shown in Fig. 1.
  • a The magnetic bar lifting mechanism drives the magnetic bar 20 to move up and down, the function is to insert or remove the magnetic bar 20 into the stirring sleeve 21;
  • the stirring sleeve driving mechanism drives the stirring sleeve 21 slowly.
  • the speed is up and down; c: the stirring sleeve driving mechanism drives the stirring sleeve 21 to quickly stir up and down; d: the deep hole plate translation mechanism drives the deep hole plate 22 to translate left and right (corresponding to the left and right translational movements after the magnetic bar 20 and the stirring sleeve 21 are combined) ; e: The magnetic rod lifting mechanism and the stirring sleeve driving mechanism cooperate to synchronize the movement, and the vertical movement of the magnetic rod 20 and the stirring sleeve 21 after the combination is realized.
  • the driving mechanism of the stirring sleeve is driven by the stepping motor to drive the stirring sleeve 21 through the screw rod and the screw nut to reciprocate on the sliding rod, thereby realizing the slow moving up and down movement of the stirring sleeve 21 and the quick stirring action.
  • the stirring action of the stirring sleeve 21 is a high frequency reciprocating movement, and the stepping motor must achieve high frequency forward and reverse rotation.
  • the energy of the motor is converted from the power supply of the system, mainly including the kinetic energy of the rotor of the motor and the electromagnetic energy stored in the armature of the motor.
  • the energy of the forward rotation of the motor must disappear, and the motor can be reversed.
  • the energy of the motor reversal must disappear and the motor can rotate forward.
  • the motor When the high frequency is reversed, the motor must be braked or decelerated frequently to achieve commutation. Most of the energy of the motor is not used for agitation, it does not form useful work, but is wasted by frequent braking, and thus is inefficient.
  • the motor has a negative effect due to the energy converted from the positive and negative energy being converted into thermal energy and mechanical energy.
  • Thermal energy causes the motor and the entire system to include elevated circuit temperatures.
  • Mechanical energy causes system vibration and noise.
  • the stepping motor will lose its step when the high frequency is greatly reversed under load, and the energy loss caused by the positive and negative motor is more serious. Therefore, when the stirring frequency is high, it is impossible to stir at the same time. If you want to achieve high frequency and large agitation, you need to use more powerful motors or more expensive motors and components, such as high-power stepper motors, servo motors, ball screws and so on. These components are tens of times more expensive than low-power stepper motors and ordinary screw. Therefore, the prior art stirring sleeve driving mechanism is difficult to achieve a high frequency and a large stirring action.
  • the sample does not work properly when it is a highly viscous liquid, or if the sample size is large, or the sample impurity content is high. Because high viscosity, or large amounts, or high impurity content samples require high frequency and large amplitude agitation, the nucleic acid can be cleaned. Otherwise, the agitation amplitude does not meet the requirements, which may result in poor purification of the nucleic acid or even failure of extraction.
  • the transmission mechanism connected to the stepping motor uses a screw rod and a screw nut, and some instruments use a timing belt transmission mechanism.
  • these two mechanisms are very noisy when moving at high frequencies.
  • the screw rod and the screw nut are high-precision transmission components, and are prone to wear failure under long-term frequent reciprocating motion, so the maintenance cost is high.
  • the timing belt will fatigue and break due to long-term frequent reciprocating motion.
  • the above-mentioned stirring sleeve driving mechanism cannot be used for samples requiring high frequency and large agitation, and has high energy consumption, low efficiency, large vibration, high noise, high cost, heavy instrument, and high maintenance rate.
  • the holes in the clamping device of the stirring sleeve frame, the magnetic rod frame and the deep hole plate are matched with the elongated round bar-shaped sliding bar, and the stirring sleeve, the magnetic bar and the deep hole plate are on the sliding bar. Reciprocating. The friction between the outer circle of the slider and the hole is large. And the long slide bar that is erected is only fixed at the end and is easy to bend. Even if the slider has a slight curvature that cannot be recognized by the naked eye, the sliding of the clamping device may not be smooth or even impossible. Therefore, the use of sliders is not a good support and guidance method.
  • the present invention provides a nucleic acid purifying apparatus, wherein the stirring sleeve driving mechanism is a crank slider mechanism, and the motor can rotate in the same direction continuously, without the need of positive and negative reversal, even if the market is the most common and economical.
  • the small power stepping motor can realize the stirring motion, avoiding a series of problems caused by the forward and reverse of the stepping motor in the prior art.
  • a nucleic acid purifying apparatus comprises a mechanical part, a control system, an operating unit and a casing, wherein the mechanical part is located at a lower part of the nucleic acid purifying device, the control system and the operating unit are located at an upper part of the instrument, the outer casing is wrapped at the outermost part of the instrument, and the mechanical part comprises a stirring sleeve driving mechanism, Stirring frame, magnetic bar lifting mechanism, magnetic bar frame, bracket or support plate, base, work table, table translation device or bracket translation device, the stirring frame is mounted on the stirring sleeve driving mechanism, and the magnetic rod frame is mounted on the magnetic In the rod lifting mechanism, the stirring sleeve driving mechanism and the magnetic rod lifting mechanism are mounted on the bracket or the supporting plate, the bracket or the supporting plate and the working table are mounted on the base, and the working table is disposed under the magnetic rod frame and the stirring sleeve frame;
  • the stirring sleeve driving mechanism comprises a stirring motor, a crank, a connecting rod, a stirring
  • the stirring motor shaft is fixedly connected with the crank, the crank and the connecting rod are rotatably connected at one end, and the other end of the connecting rod and the stirring sleeve slider
  • the rotatably connected, the stirring sleeve is fixed on the stirring sleeve slider, and the stirring sleeve slider is slidably connected with the stirring sleeve rail.
  • the nucleic acid purifier further includes a bracket lifting device, and the bracket lifting device comprises a bracket lifting motor, an intermediate bracket, a bracket lifting screw, a bracket lifting screw nut, a bracket lifting slider, a bracket lifting rail, and a bracket lifting
  • the motor is mounted on the intermediate bracket, the bracket lifting screw is connected with the bracket lifting motor shaft, the bracket lifting screw nut is set on the bracket lifting screw, the bracket lifting screw nut is connected with the support plate, and the bracket is lifted and slid
  • the block is mounted on the support plate, the bracket lifting rail is fixed on the intermediate bracket, and the bracket lifting slider is slidably connected with the bracket lifting rail.
  • the bracket translation device of the present invention comprises a bracket translation motor, a bracket translation screw, a bracket translation screw nut, a bracket translation slider, a bracket translation rail, a bracket translation motor mounted on the base, and a bracket translation
  • the lead screw is connected to the bracket translation motor shaft
  • the bracket translation screw nut is set on the bracket translation screw
  • the bracket translation screw nut is connected with the bracket lifting device
  • the bracket translation slider is mounted on the bracket lifting device.
  • the bracket translation rail is mounted on the base, and the bracket translation slider is slidably coupled to the bracket translation rail.
  • the magnetic rod lifting mechanism comprises a magnetic rod lifting motor, a magnetic rod lifting screw, a magnetic rod lifting screw nut, a magnetic rod lifting slider, a magnetic rod lifting rail, a magnetic rod lifting motor shaft and a magnetic rod lifting screw, and the magnetic rod lifting
  • the screw nut is set on the magnetic rod lifting screw
  • the magnetic rod lifting screw nut is connected with the magnetic rod frame
  • the magnetic rod lifting slider is fixed on the magnetic rod frame
  • the magnetic rod lifting slider is slidably connected with the magnetic rod lifting rail .
  • the stirring sleeve driving mechanism further comprises a blocking piece, a position sensor and a bearing, the blocking piece is fixed on the crank, the position sensor is fixed beside the crank, the blocking piece is a thin plate, the thickness direction thereof passes through the groove on the position sensor, and the bearing is installed in the hole of the connecting rod Inside.
  • the flap is a right-angled fan.
  • the slider driving mechanism, the magnetic bar lifting mechanism, the bracket translation device, and the slider and the rail mechanism in the bracket lifting device are both ball linear guide mechanisms.
  • crank and connecting rod of the stirring sleeve drive mechanism are made of aluminum alloy.
  • the ratio of the length of the crank to the connecting rod is less than 1:1, and the frequency of the stirring motor is 0-20 Hz.
  • the ratio of the length of the crank to the connecting rod is 1:4 to 1:6, and the frequency of the stirring motor is 2 to 8 Hz.
  • the stirring sleeve driving mechanism is changed to a crank slider mechanism.
  • the stirring motor only needs to rotate continuously in the same direction, and the lifting and stirring action of the stirring sleeve can be realized without positive and negative reversal. High energy utilization, low system temperature rise, low vibration and noise, and completely eliminate the noise generated by the screw and timing belt during mixing.
  • the instrument of the invention has small vibration and does not need to increase the weight of the base, so the instrument of the invention has less than 1/2 weight loss compared with the conventional instrument, and is convenient to carry.
  • the crank slider mechanism of the invention can drive the stirring sleeve to realize a high frequency and a large stirring action, and when the sample is a high viscosity or high impurity liquid, the motor frequency is increased, the stirring amplitude is increased (the crank length is increased), and the stirring can be enhanced. Strength to ensure the quality of nucleic acid purification for specific samples.
  • the instrument of the invention has high energy utilization rate, and only needs a common low-power motor, a crank-slider transmission mechanism, and a low-power power source, and the component cost is low; the crank slider mechanism is simpler than the screw rod or the timing belt mechanism, More durable.
  • the two inner holes of the connecting rod are provided with bearings. And the movement of the stirring sleeve is supported and guided by the ball linear guide mechanism, so the mutual rotation or mutual sliding between the parts in the mechanism is smooth, the parts wear is small, and the instrument has a long service life.
  • the stirring action runs through the entire nucleic acid purification process and is the most influential part of the purification effect.
  • the improvement of the stirring sleeve driving mechanism of the invention plays a key role in improving the performance of the nucleic acid purifying apparatus.
  • the present invention is specifically provided with a bracket lifting device.
  • the bracket lifting device drives the magnetic rod frame and the stirring sleeve frame mounted on the bracket device to simultaneously lift and lower, thereby ensuring that the magnetic rod and the stirring sleeve are completely synchronized and raised. It avoids the risk of the magnetic beads falling when the two mechanisms are combined and driven, which significantly enhances the reliability of the instrument.
  • the carriage translating device of the present invention replaces the table translating device disposed under the table in the prior art.
  • the cradle translating device drives the stir bar on the cradle device to translate with the magnetic bar for reliable operation.
  • the power mechanism of the whole instrument is located at the back of the base, the instrument is safer to use, the layout is more compact and beautiful.
  • the ball linear guide mechanism is used as the supporting and guiding mechanism of the moving member.
  • the rolling friction between the guide rail and the slider is smaller, which makes the movement of the magnetic rod and the stirring sleeve smoother, more stable and more reliable.
  • the nucleic acid purifying instrument provided by the invention improves the stirring sleeve driving mechanism, and can adopt high-cost components to perform high-frequency stirring. High energy utilization, low vibration, low noise, light weight, simple structure, convenient maintenance, low instrument cost, long service life and more reliable work.
  • Figure 1 is a schematic diagram of the basic operation of the nucleic acid purifying apparatus
  • Figure 2 is an outline view of the nucleic acid purifying apparatus of the present invention.
  • Figure 3 is a structural view showing the mechanical part of the nucleic acid purifying apparatus of the present invention.
  • Figure 4 is a plan view showing the mechanical part of the nucleic acid purifying apparatus of the present invention.
  • Figure 5 is a right side view of the mechanical portion of the nucleic acid purifying apparatus of the present invention.
  • Figure 6 is a perspective view of the driving mechanism of the stirring sleeve of the nucleic acid purifying apparatus of the present invention.
  • Figure 7 is a left side view of the stirring sleeve driving mechanism of the nucleic acid purifying apparatus of the present invention.
  • Figure 8 is a rear elevational view of the stirring sleeve driving mechanism of the nucleic acid purifying apparatus of the present invention.
  • Figure 9 is a perspective view of the carrier device of the nucleic acid purifying apparatus of the present invention.
  • the nucleic acid purifier is composed of a mechanical part 1, a control system 2, an operation unit 3, and a casing 4.
  • the mechanical part 1 is located at the lower part of the nucleic acid purifier, the control system 2 and the operating unit 3 are located at the upper portion, and the outer casing 4 is wrapped around the outermost part of the instrument.
  • Mechanical part 1 is the core component of the nucleic acid purifier.
  • the lifting and stirring operation of the stirring sleeve 21 is performed by the stirring sleeve driving mechanism 5.
  • the lifting and lowering of the magnetic bar 20 is performed by the magnetic bar lifting mechanism 6.
  • the stirring sleeve drive mechanism 5 and the magnetic bar lifting mechanism 6 are mounted on the support plate 12 to constitute the bracket device 9.
  • the lifting and lowering of the magnetic bar 20 after the combination of the stirring sleeve 21 and the stirring sleeve 21 are respectively performed by the carriage lifting device 8 and the carriage translation device 7 to drive the carriage device 9.
  • the above mechanism and the table 14 on which the deep hole plate 22 is placed are disposed on the base 13.
  • the magnetic bar lifting mechanism 6 is driven by a magnetic bar lifting motor 61 mounted on the upper front surface of the support plate 12, and the magnetic bar lifting motor 61 is fixed to the support plate 12 by a magnetic bar lifting motor mounting plate 65.
  • the magnetic rod lifting motor 61 shaft drives the magnetic rod lifting screw 62 connected underneath to rotate (or the magnetic rod lifting screw 62 is integrated with the magnetic rod lifting motor 61 shaft), and the magnetic rod lifting screw nut 63 is in the magnetic rod lifting wire
  • the rod 62 is driven up and down.
  • the magnetic rod frame 11 is fixedly connected to the magnetic rod lifting screw nut 63, and the magnetic rod lifting rod nut 63 drives the magnetic rod holder 11 to move up and down.
  • the magnetic bar frame 11 is fixedly connected to the magnetic bar lifting and lowering slider 64, and the magnetic bar lifting and lowering slider 64 is slidably connected to the stirring sleeve rail 55 mounted on the supporting plate 12, so that the magnetic bar frame 11 moves up and down along the stirring sleeve guide 55, that is, the figure
  • the operation of a of the magnetic rod holder 11 shown in Fig. 9 is a function of inserting and removing the magnetic rod 20 into the stirring sleeve 21.
  • the sheet 66 fixed on the magnetic rod frame 11 transmits the position signal of the magnetic rod lifting mechanism 6 to the control system 2 when passing through the position sensor 57 mounted on the side of the magnetic rod lifting screw 62 during the movement, and the control system 2
  • the magnetic bar lifting motor 61 is then controlled to control the lifting and lowering of the magnetic bar 20.
  • the screw nut mechanism composed of the magnetic rod lifting screw 62 and the magnetic rod lifting screw nut 63 may be a sliding screw nut mechanism, a ball screw nut mechanism, a synchronous belt reciprocating mechanism, a rack and pinion mechanism, and the like. .
  • the power source of the stirring sleeve drive mechanism 5 is the stirring motor 51.
  • the agitating motor 51 is mounted on the lower portion of the back surface of the support plate 12, the shaft of the agitating motor 51 passes through the hole of the support plate 12, the crank 52 is mounted on the shaft of the agitating motor 51, the crank 52 is located on the front surface of the mounting plate, and the other end of the crank 52 is connected to the connecting rod
  • One end of the 53 is hinged by a pin, and the other end of the link 53 is hinged to the stirring frame 10 through a pin.
  • a rolling bearing 58 is mounted in the bore of the connecting rod 53 that cooperates with the pin. The rolling bearing 58 serves to support the pin and reduce wear of the pin.
  • the stirring sleeve 10 is fixedly connected with the stirring sleeve slider 54 , and the stirring sleeve slider 54 is slidably connected with the stirring sleeve rail 55 , so the stirring motor 51 drives the stirring sleeve frame 10 to perform lifting and stirring along the stirring sleeve rail 55 through the crank slider mechanism. That is, the b and c of the stirring sleeve 21 shown in Fig. 6 operate. The action of b and c acts to agitate the sleeve 21 into the deep hole of the deep well plate 22, stir the magnetic beads and liquid, and exit the deep hole.
  • the shaft of the stirring motor 51 is continuously rotated 360 degrees, and the amplitude of the stirring frame 10 is equal to twice the length between the two shaft holes of the crank 52.
  • the amplitude of the agitation rack 10 in the elution phase is smaller than that in the pyrolysis and washing stages, so the agitating motor 51 needs to be positively inverted within a certain angle range in the elution phase.
  • the control signal from the control system 2 to the forward and reverse rotation of the agitating motor 51 comes from the flap 56 mounted on the crank 52 and the photoelectric position sensor 57 below the crank 52 that cooperates with the flap 56.
  • the flap 56 is preferably a right-angled sector.
  • the elution phase takes about 1/10 of the total nucleic acid purification time, so the motor reversal at this stage has little effect on the noise of the nucleic acid purifier.
  • the crank 52 and the connecting rod 53 of the stirring sleeve drive mechanism 5 are made of aluminum alloy, which can effectively reduce the weight of the moving parts and reduce the inertial force of the stirring sleeve 21.
  • the ratio of the length of the crank 52 to the connecting rod 53 is less than 1:1. Because the connecting rod 53 is too long, the mass of the connecting rod 53 is increased, and the space occupied by the mechanism is large. When the connecting rod 53 is too short, the side pressure of the stirring sleeve slider 54 is caused. Increasing, it is preferable that the ratio of the length of the crank 52 to the link 53 is 1:4 to 1:6.
  • the stirring frequency of the stirring motor 51 is selected to be 0 to 20 Hz. However, according to the test results of various samples, it is considered that the stirring frequency is in the range of 2 to 8 Hz, which can achieve the best stirring effect and save the nucleic acid purification time.
  • the stirring sleeve driving mechanism 5 and the magnetic bar lifting mechanism 6 are both mounted on the support plate 12, the stirring sleeve driving mechanism 5 is located below the magnetic bar lifting mechanism 6, and the stirring sleeve 10 is located below the magnetic bar frame 11.
  • the magnetic rod frame 11 and the stirring sleeve 10 are located directly above the deep orifice plate 22 on the table 14.
  • the shutter 16 mounted on the support plate 12 separates the agitator frame 10 and the magnetic bar frame 11 at the front of the base 13 from the other components at the rear.
  • the magnetic bar lifting mechanism 6, the magnetic bar frame 11, the stirring sleeve driving mechanism 5, the stirring jacket 10, the support plate 12, and the shielding plate 16 collectively constitute a bracket device 9.
  • the bracket lifting device 8 is composed of a bracket lifting motor 81, a bracket lifting motor mounting plate 82, a bracket lifting screw 83, a bracket lifting screw nut 84, and an intermediate bracket 85.
  • the support plate drive member 86, the bracket lifting slider 87, the bracket lifting rail 88, and the bent sheet 89 are formed.
  • the carriage lift motor 81 is attached to the upper portion of the intermediate bracket 85 via the bracket lift motor mounting plate 82.
  • the bracket lifting screw 83 is fixedly coupled to the bracket lifting motor 81 (or the bracket lifting screw 83 is integrated with the bracket lifting motor 81 shaft).
  • the bracket lift screw nut 84 and the support plate drive member 86 are integrally fixed by bolts. As shown in FIG.
  • the support plate driving member 86 is fastened to the side of the support plate 12 in the bracket device 9, and is fastened.
  • the carriage lifting motor 81 drives the carriage lifting screw nut 84 up and down by the carrier lifting screw 83, and the carrier lifting screw nut 84 then drives the carriage device 9 up and down through the support plate 12.
  • a bracket lifting slider 87 is attached to the front surface of the support plate 12 of the bracket device 9, and the bracket lifting slider 87 is slidably coupled to the bracket lifting rail 88 fastened to the intermediate bracket 85 so that the bracket device 9 can be Stabilizing smoothly up and down, during the lifting process of the bracket device 9, the magnetic bar 20 is inserted into the bottom of the stirring sleeve 21, and the magnetic bar 20 and the stirring sleeve 21 are moved up and down, that is, the e action shown in FIG. The action sucks the magnetic beads into and into the deep holes of the deep well plate 22.
  • the bent sheet 89 fixed to the support plate driving member 86 transmits a position signal to the control system 2 via the photoelectric position sensor 57 fixed to the intermediate holder 85, which in turn controls the carriage lifting motor 81.
  • the bracket lifting device 8 of the present invention realizes that the magnetic bar 20 and the stirring sleeve 21 are combined (the magnetic rod 20 is inserted into the bottom of the stirring sleeve 21), and then moved up and down together, and the bracket lifting motor 81 is independently driven, the displacement is convenient to control, and the movement is performed.
  • the process of magnetic beads is safe and reliable.
  • the screw nut mechanism composed of the bracket lifting screw 83 and the bracket lifting screw nut 84 may be a sliding screw nut mechanism, a ball screw nut mechanism, a timing belt reciprocating mechanism, a rack and pinion mechanism, and the like.
  • the power source of the carriage translating device 7 is a carriage translation motor 71.
  • the carriage translation motor 71 is fixed on the base 13 by the bracket translation motor mounting plate 72.
  • the carriage translation motor 71 drives the carriage translation screw 73 to rotate, and the carriage translation screw 73 drives the carriage to translate the screw nut 74 horizontally. mobile.
  • One side of the drive bending plate 75 is fixedly coupled to the bracket translation screw nut 74, and the other side of the bending is bolted to the intermediate bracket 85 in the bracket lifting mechanism.
  • the carriage translation slider 76 is mounted on the intermediate bracket 85, and the carriage translation guide 77 is fixed to the base 13.
  • the carriage translation slider 76 is slidably coupled to the carriage translation rail 77 in a horizontal direction, and the carriage translation screw nut 74 drives the intermediate bracket 85 to horizontally move along the carriage translation guide 77 by the drive bending plate 75.
  • the carriage lifting device 8 where the intermediate bracket 85 is located and the bracket device 9 are not moved in the horizontal direction, and the two are integrated. Therefore, the driving curved plate 75 drives the bracket device 9 to move horizontally.
  • the magnetic bar 20 is inserted into the bottom of the stirring sleeve 21, and the horizontal movement of the magnetic bar 20 and the stirring sleeve 21 is the same as that of FIG. The d action shown.
  • the d action cooperates with the a and e actions described above to complete the handling of the magnetic beads.
  • the horizontal movement of the carriage device 9 is smoother due to the arrangement of the carriage translation slider 76 and the carriage translation guide 77.
  • the bent sheet 2 78 fixed to the drive bending plate 75 cooperates with the photoelectric position sensor 57 to realize position signal transmission of the horizontal movement of the carriage device 9.
  • the screw nut mechanism composed of the bracket translation screw 73 and the bracket translation screw nut 74 may be a sliding screw nut mechanism, a ball screw nut mechanism, a timing belt reciprocating mechanism, a rack and pinion mechanism, and the like. .
  • the cradle lifting device 8 and the cradle translating device 7 can also drive the cradle device 9 to perform lifting and translation to complete some auxiliary actions of the nucleic acid purification process.
  • the slider and the rail mechanism in the stirring sleeve driving mechanism 5, the magnetic rod lifting mechanism 6, the bracket translation device 7, and the bracket lifting device 8 are rolling linear guide mechanisms, and the friction between the guide rail and the slider is rolling friction The resistance is smaller and the movement of the moving parts is smoother and smoother.
  • the magnetic bar lifting and lowering mechanism 6 in the cradle device 9 realizes an operation (a operation) in which the magnetic bar 20 is separately raised and lowered, and the magnetic bar 20 is inserted or taken out of the agitating sleeve 21.
  • the bracket lifting device 8 and the bracket translation device 7 respectively realize the up and down movement and translation movement (d action and e action) after the magnetic bar 20 and the stirring sleeve 21 are combined, and the a, d, and e actions are combined to complete the magnetic bead handling work. .
  • the stirring sleeve driving mechanism 5 can drive the stirring sleeve 21 to move up and down separately and perform stirring (b action and c action), and complete the mixing operation of the stirring sleeve 21 into and out of the deep hole and the magnetic beads and the liquid in the deep hole.
  • the control system 2 sequentially controls the operation of each motor based on the signal of the photoelectric position sensor 57 to complete the nucleic acid purification process.
  • the stirring sleeve driving mechanism 5, the magnetic rod lifting mechanism 6, the bracket translation device 7, and the bracket lifting device 8 are four independently controllable and movable components, and can complete various actions and action sequences by changing the program of the control system. Combine to realize the nucleic acid purification process to meet the individual needs of users.

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Abstract

A nucleic acid purifier, comprising a mechanical part (1), a control system (2), an operation unit (3), and a casing (4). The mechanical part comprises: a stirring sleeve driving mechanism (5), a bar magnet lifting mechanism (6), a bracket lifting device (8), a bracket translation device (7), a stirring sleeve rack (10), a bar magnet rack (11), a base (12), and a worktable (14). The stirring sleeve driving mechanism (5) is a slider-crank mechanism; a stirring motor rotates in the same direction continuously, and forward and reverse rotation is not required; the stirring sleeve rack (10) fixed on a stirring sleeve slider is driven by the stirring sleeve slider (54) to move up and down along a stirring sleeve guide rail (55) and to stir samples; the bracket lifting device can drive a bracket device (9), and further drive bar magnets (20) and stirring sleeves (21) to go up and down synchronously. The nucleic acid purifier can stir samples at a high frequency and large amplitude, and can effectively improve nucleic acid purification effect. The nucleic acid purifier is simple in structure, reliable in working, low in power consumption, small in vibration and noise and low in cost, and is conveniently maintained.

Description

核酸纯化仪Nucleic acid purification instrument 技术领域Technical field
本发明涉及生物仪器领域,尤其涉及基于纳米磁珠的核酸纯化自动装置。The invention relates to the field of biological instruments, in particular to a nucleic acid purification automatic device based on nano magnetic beads.
背景技术Background technique
核酸(DNA或RNA)广泛存在于动植物体内。在临床诊断与治疗,或法医学鉴定,或基因筛查与重组等工作中,人们需要将核酸从样本(血液、唾液或其他组织)中提取出来,提取核酸的过程也称为核酸纯化。核酸纯化的效果好坏直接影响研究和诊断的进程和结果,因此核酸纯化技术是生物科技中一项重要技术。Nucleic acids (DNA or RNA) are widely found in animals and plants. In clinical diagnosis and treatment, or forensic identification, or genetic screening and recombination, people need to extract nucleic acids from samples (blood, saliva or other tissues), and the process of extracting nucleic acids is also called nucleic acid purification. The effect of nucleic acid purification directly affects the progress and results of research and diagnosis, so nucleic acid purification technology is an important technology in biotechnology.
目前常见的一种核酸纯化方法是磁棒法,磁棒法是利用磁棒吸附纳米磁珠,纳米磁珠吸附核酸,将核酸从样本中分离出来。磁棒法的工作原理如图1所示,将磁棒20、搅拌套21、深孔板22从上到下依次布置;其中,深孔板22上有一组深孔,这组深孔包含裂解液孔221、磁珠孔222、洗涤液孔223(可设置多个洗涤液孔)、洗脱液孔224,分别存放相应的试剂。核酸纯化流程的具体步骤是:将样本滴入裂解液中裂解出核酸--收集磁珠到裂解液孔--磁珠与核酸结合--收集磁珠至洗涤孔(可多次洗涤)--收集磁珠到洗脱孔--洗脱后回收磁珠,最后核酸留在洗脱液中。为了便于上述流程实现自动化操作,需要核酸纯化仪实现如图1所示的基本动作,即:(1)磁棒20的上下移动a,(2)搅拌套21的上下移动b及搅拌动作c,(3)磁棒20插入搅拌套21两者合体后的上下移动e,(4)磁棒20插入搅拌套21两者合体后的平移动作d。A commonly used nucleic acid purification method is a magnetic rod method. The magnetic rod method uses a magnetic rod to adsorb nano magnetic beads, and the nano magnetic beads adsorb nucleic acids to separate nucleic acids from the sample. The working principle of the magnetic bar method is as shown in FIG. 1. The magnetic bar 20, the stirring sleeve 21 and the deep hole plate 22 are arranged in order from top to bottom; wherein the deep hole plate 22 has a set of deep holes, and the deep holes include cracking. The liquid hole 221, the magnetic bead hole 222, the washing liquid hole 223 (a plurality of washing liquid holes may be provided), and the eluent liquid hole 224 respectively store the corresponding reagents. The specific steps of the nucleic acid purification process are: dropping the sample into the lysate to cleave the nucleic acid--collecting the magnetic beads to the lysate well--the magnetic beads are combined with the nucleic acid--collecting the magnetic beads to the washing holes (multiple washings)- The magnetic beads are collected to the elution well--the magnetic beads are recovered after elution, and finally the nucleic acid remains in the eluate. In order to facilitate the automatic operation of the above process, the nucleic acid purifier is required to realize the basic actions as shown in FIG. 1, namely: (1) the up and down movement of the magnetic bar 20 a, (2) the up and down movement of the stirring sleeve 21 and the stirring action c, (3) The vertical movement e after the magnet bar 20 is inserted into the mixing sleeve 21, and (4) the translational action d after the magnetic rod 20 is inserted into the mixing sleeve 21.
中国发明专利CN103897987B公开了一种基于纳米磁珠的核酸自动提取装置,核酸提取装置主要由基座、安装在基座上的三个机构组成。所述三个机构分别是:磁棒升降机构、搅拌套驱动机构和深孔板平移机构。三个机构均是由步进电机、丝杆螺母机构,起支撑和导向作用的滑杆组成。上述三个机构分别实现的动作见图1,a:磁棒升降机构驱动磁棒20上下移动,作用是将磁棒20插入或取出搅拌套21;b:搅拌套驱动机构驱动搅拌套21的慢速上下移动;c:.搅拌套驱动机构驱动搅拌套21快速上下搅拌;d:深孔板平移机构带动深孔板22左右平移(相当于磁棒20与搅拌套21合体后的左右平移动作);e:磁棒升降机构和搅拌套驱动机构配合,同步动作,实现磁棒20与搅拌套21合体后的上下移动。Chinese invention patent CN103897987B discloses an automatic nucleic acid extraction device based on nano magnetic beads. The nucleic acid extraction device is mainly composed of a base and three mechanisms mounted on the base. The three mechanisms are: a magnetic bar lifting mechanism, a stirring sleeve driving mechanism and a deep hole plate translation mechanism. The three mechanisms are composed of a stepping motor, a screw nut mechanism, and a sliding bar that supports and guides. The actions achieved by the above three mechanisms are shown in Fig. 1. a: The magnetic bar lifting mechanism drives the magnetic bar 20 to move up and down, the function is to insert or remove the magnetic bar 20 into the stirring sleeve 21; b: the stirring sleeve driving mechanism drives the stirring sleeve 21 slowly. The speed is up and down; c: the stirring sleeve driving mechanism drives the stirring sleeve 21 to quickly stir up and down; d: the deep hole plate translation mechanism drives the deep hole plate 22 to translate left and right (corresponding to the left and right translational movements after the magnetic bar 20 and the stirring sleeve 21 are combined) ; e: The magnetic rod lifting mechanism and the stirring sleeve driving mechanism cooperate to synchronize the movement, and the vertical movement of the magnetic rod 20 and the stirring sleeve 21 after the combination is realized.
上述核酸提取装置的缺点是:The disadvantages of the above nucleic acid extraction device are:
第一、搅拌套驱动机构由步进电机通过丝杆及丝杆螺母驱动搅拌套21在滑杆上进行往复运动,实现搅拌套21的慢速上下移动及快速搅拌动作。其中,搅拌套21的搅拌动作是高频率 往复移动,步进电机必须高频率的正反转才能实现。First, the driving mechanism of the stirring sleeve is driven by the stepping motor to drive the stirring sleeve 21 through the screw rod and the screw nut to reciprocate on the sliding rod, thereby realizing the slow moving up and down movement of the stirring sleeve 21 and the quick stirring action. Among them, the stirring action of the stirring sleeve 21 is a high frequency reciprocating movement, and the stepping motor must achieve high frequency forward and reverse rotation.
搅拌套进行搅拌时,电机的能量由系统的供电转化而来,主要包括电机转子的动能和电机电枢中存储的电磁能。根据牛顿定律,电机正转的能量必须消失,电机才能反转;反之,电机反转的能量必须消失,电机才能正转。在高频正反转时,电机必须频繁制动或减速才能实现换向。电机的大部分能量不是用于搅拌,没有形成有用功,而是被频繁制动所浪费,因而效率低下。When the mixing sleeve is stirred, the energy of the motor is converted from the power supply of the system, mainly including the kinetic energy of the rotor of the motor and the electromagnetic energy stored in the armature of the motor. According to Newton's law, the energy of the forward rotation of the motor must disappear, and the motor can be reversed. Conversely, the energy of the motor reversal must disappear and the motor can rotate forward. When the high frequency is reversed, the motor must be braked or decelerated frequently to achieve commutation. Most of the energy of the motor is not used for agitation, it does not form useful work, but is wasted by frequent braking, and thus is inefficient.
根据能量守恒定律,能量既不能凭空产生,也不会凭空消失,它只会从一种形式转化为另一种形式,或者从一个物体转移到其它物体。在这里,电机由于正反转浪费的能量转化为热能和机械能而产生负作用。热能导致电机及整个系统包括电路系统温度升高。机械能则导致系统振动和噪音。According to the law of conservation of energy, energy can neither be produced out of thin air nor disappeared out of thin air. It can only be transformed from one form to another, or from one object to another. Here, the motor has a negative effect due to the energy converted from the positive and negative energy being converted into thermal energy and mechanical energy. Thermal energy causes the motor and the entire system to include elevated circuit temperatures. Mechanical energy causes system vibration and noise.
为了降低振动和噪音,现有仪器不得不采用较重的仪器底座,来降低共振频率,所以仪器较重,导致运输的难度和成本加大。In order to reduce vibration and noise, existing instruments have to use a heavier instrument base to reduce the resonance frequency, so the instrument is heavier, resulting in increased difficulty and cost of transportation.
受到步进电机动态特性的制约,步进电机在带载荷下高频率大幅度正反转时会失步,此时电机正反转带来的能量损失更严重。所以当搅拌频率较高时,无法同时大幅度搅拌。如果要实现高频率大幅度搅拌,就要选用更大功率的电机或更昂贵的电机及零部件,比如大功率步进电机、伺服电机、滚珠丝杆等。这些部件相对小功率步进电机和普通丝杆,成本会增加数十倍。所以现有技术的搅拌套驱动机构难以实现高频率大幅度的搅拌动作。其结果是,当样本为高粘度液体、或样本量较大、或样本杂质含量高时无法正常工作。因为高粘度、或量较大、或杂质含量高的样本需要高频率大振幅的搅拌,才能将核酸清洗干净。否则,搅拌振幅达不到要求,会造成核酸纯化效果差甚至提取失败。Constrained by the dynamic characteristics of the stepper motor, the stepping motor will lose its step when the high frequency is greatly reversed under load, and the energy loss caused by the positive and negative motor is more serious. Therefore, when the stirring frequency is high, it is impossible to stir at the same time. If you want to achieve high frequency and large agitation, you need to use more powerful motors or more expensive motors and components, such as high-power stepper motors, servo motors, ball screws and so on. These components are tens of times more expensive than low-power stepper motors and ordinary screw. Therefore, the prior art stirring sleeve driving mechanism is difficult to achieve a high frequency and a large stirring action. As a result, the sample does not work properly when it is a highly viscous liquid, or if the sample size is large, or the sample impurity content is high. Because high viscosity, or large amounts, or high impurity content samples require high frequency and large amplitude agitation, the nucleic acid can be cleaned. Otherwise, the agitation amplitude does not meet the requirements, which may result in poor purification of the nucleic acid or even failure of extraction.
上述搅拌套驱动机构中,步进电机所连接的传动机构使用丝杆与丝杆螺母,也有的仪器使用同步带传动机构。这两种机构在高频率往返运动时噪音非常大。而且丝杆与丝杆螺母是高精度的传动部件,在长期频繁的往复动作下,容易磨损失效,因此维修成本较高。同步带会因为长期频繁往复运动而疲劳、断裂。In the above-mentioned stirring sleeve driving mechanism, the transmission mechanism connected to the stepping motor uses a screw rod and a screw nut, and some instruments use a timing belt transmission mechanism. These two mechanisms are very noisy when moving at high frequencies. Moreover, the screw rod and the screw nut are high-precision transmission components, and are prone to wear failure under long-term frequent reciprocating motion, so the maintenance cost is high. The timing belt will fatigue and break due to long-term frequent reciprocating motion.
所以,上述搅拌套驱动机构,不能用于需要高频大幅度搅拌的样本,且能耗大,效率低、振动大、噪音大、成本高、仪器重,维修率高。Therefore, the above-mentioned stirring sleeve driving mechanism cannot be used for samples requiring high frequency and large agitation, and has high energy consumption, low efficiency, large vibration, high noise, high cost, heavy instrument, and high maintenance rate.
第二、核酸纯化过程中,有一个动作多次执行,磁棒与搅拌套合体后一起升降,即图1的e动作。现有技术中上述动作依靠磁棒升降机构和搅拌套驱动机构配合,上下同步移动完成。如果两个机构稍不同步,则会将带有核酸的磁珠遗落在深孔外,造成核酸提取中断或失败。所以这种动作方式存在风险,导致仪器工作不可靠。Second, during the nucleic acid purification process, one action is performed multiple times, and the magnetic bar and the stirring sleeve are combined and lifted together, that is, the e action of FIG. In the prior art, the above action is coordinated by the magnetic rod lifting mechanism and the stirring sleeve driving mechanism, and the vertical movement is completed. If the two mechanisms are slightly out of sync, the magnetic beads with nucleic acids will be left outside the deep well, causing the nucleic acid extraction to be interrupted or failed. Therefore, this type of action is risky, resulting in unreliable instrument operation.
第三、现有技术中,搅拌套架、磁棒架、深孔板的夹持装置上的孔与细长的圆棒形滑杆配合,搅拌套、磁棒、深孔板在滑杆上往复移动。滑杆外圆与孔的摩擦力较大。并且竖立设置的长滑杆仅端部固定,容易弯曲。滑杆即使有肉眼不能识别的极小弯曲,也会使夹持装置的滑动不顺畅,甚至无法动作。因此,运用滑杆不是好的支撑和导向方法。Third, in the prior art, the holes in the clamping device of the stirring sleeve frame, the magnetic rod frame and the deep hole plate are matched with the elongated round bar-shaped sliding bar, and the stirring sleeve, the magnetic bar and the deep hole plate are on the sliding bar. Reciprocating. The friction between the outer circle of the slider and the hole is large. And the long slide bar that is erected is only fixed at the end and is easy to bend. Even if the slider has a slight curvature that cannot be recognized by the naked eye, the sliding of the clamping device may not be smooth or even impossible. Therefore, the use of sliders is not a good support and guidance method.
发明内容Summary of the invention
针对上述现有技术的缺点或不足,本发明提供一种核酸纯化仪,其搅拌套驱动机构为曲柄滑块机构,电机可以连续同一方向旋转,不需要正反转,即使采用市场最常见最经济的小功率步进电机就可以实现搅拌运动,避免了现有技术中步进电机正反转带来的一系列问题。In view of the above-mentioned shortcomings or deficiencies of the prior art, the present invention provides a nucleic acid purifying apparatus, wherein the stirring sleeve driving mechanism is a crank slider mechanism, and the motor can rotate in the same direction continuously, without the need of positive and negative reversal, even if the market is the most common and economical. The small power stepping motor can realize the stirring motion, avoiding a series of problems caused by the forward and reverse of the stepping motor in the prior art.
本发明的技术方案是,The technical solution of the present invention is
一种核酸纯化仪,包括机械部分、控制系统、操作单元、外壳,机械部分位于核酸纯化仪下部,控制系统和操作单元位于仪器上部,外壳包裹于仪器最外面,机械部分包括搅拌套驱动机构、搅拌套架、磁棒升降机构、磁棒架、支架或支撑板、基座、工作台、工作台平移装置或支架平移装置,搅拌套架安装于搅拌套驱动机构上,磁棒架安装于磁棒升降机构上,搅拌套驱动机构与磁棒升降机构安装于支架或支撑板上,支架或支撑板与工作台安装于基座上,工作台设置于磁棒架和搅拌套架下方;其特征在于,搅拌套驱动机构包括搅拌电机、曲柄、连杆、搅拌套滑块、搅拌套导轨,搅拌电机轴与曲柄固定连接,曲柄与连杆一端可转动连接,连杆另一端与搅拌套滑块可转动连接,搅拌套架固定在搅拌套滑块上,搅拌套滑块与搅拌套导轨滑动连接。A nucleic acid purifying apparatus comprises a mechanical part, a control system, an operating unit and a casing, wherein the mechanical part is located at a lower part of the nucleic acid purifying device, the control system and the operating unit are located at an upper part of the instrument, the outer casing is wrapped at the outermost part of the instrument, and the mechanical part comprises a stirring sleeve driving mechanism, Stirring frame, magnetic bar lifting mechanism, magnetic bar frame, bracket or support plate, base, work table, table translation device or bracket translation device, the stirring frame is mounted on the stirring sleeve driving mechanism, and the magnetic rod frame is mounted on the magnetic In the rod lifting mechanism, the stirring sleeve driving mechanism and the magnetic rod lifting mechanism are mounted on the bracket or the supporting plate, the bracket or the supporting plate and the working table are mounted on the base, and the working table is disposed under the magnetic rod frame and the stirring sleeve frame; The stirring sleeve driving mechanism comprises a stirring motor, a crank, a connecting rod, a stirring sleeve slider and a stirring sleeve rail. The stirring motor shaft is fixedly connected with the crank, the crank and the connecting rod are rotatably connected at one end, and the other end of the connecting rod and the stirring sleeve slider The rotatably connected, the stirring sleeve is fixed on the stirring sleeve slider, and the stirring sleeve slider is slidably connected with the stirring sleeve rail.
核酸纯化仪还包括托架升降装置,托架升降装置包括托架升降电机、中间支架、托架升降丝杆、托架升降丝杆螺母、托架升降滑块、托架升降导轨,托架升降电机安装于中间支架上,托架升降丝杆与托架升降电机轴连接,托架升降丝杆螺母套装于托架升降丝杆上,托架升降丝杆螺母与支撑板连接,托架升降滑块安装在支撑板上,托架升降导轨固定在中间支架上,托架升降滑块与托架升降导轨滑动连接。The nucleic acid purifier further includes a bracket lifting device, and the bracket lifting device comprises a bracket lifting motor, an intermediate bracket, a bracket lifting screw, a bracket lifting screw nut, a bracket lifting slider, a bracket lifting rail, and a bracket lifting The motor is mounted on the intermediate bracket, the bracket lifting screw is connected with the bracket lifting motor shaft, the bracket lifting screw nut is set on the bracket lifting screw, the bracket lifting screw nut is connected with the support plate, and the bracket is lifted and slid The block is mounted on the support plate, the bracket lifting rail is fixed on the intermediate bracket, and the bracket lifting slider is slidably connected with the bracket lifting rail.
本发明的托架平移装置包括托架平移电机、托架平移丝杆、托架平移丝杆螺母、托架平移滑块、托架平移导轨,托架平移电机安装于基座上,托架平移丝杆与托架平移电机轴连接,托架平移丝杆螺母套装于托架平移丝杆上,托架平移丝杆螺母与托架升降装置连接,托架平移滑块安装在托架升降装置上,托架平移导轨安装在基座上,托架平移滑块与托架平移导轨滑动连接。The bracket translation device of the present invention comprises a bracket translation motor, a bracket translation screw, a bracket translation screw nut, a bracket translation slider, a bracket translation rail, a bracket translation motor mounted on the base, and a bracket translation The lead screw is connected to the bracket translation motor shaft, the bracket translation screw nut is set on the bracket translation screw, the bracket translation screw nut is connected with the bracket lifting device, and the bracket translation slider is mounted on the bracket lifting device. The bracket translation rail is mounted on the base, and the bracket translation slider is slidably coupled to the bracket translation rail.
磁棒升降机构包括磁棒升降电机、磁棒升降丝杆、磁棒升降丝杆螺母、磁棒升降滑 块、磁棒升降导轨,磁棒升降电机轴与磁棒升降丝杆连接,磁棒升降丝杆螺母套装于磁棒升降丝杆上,磁棒升降丝杆螺母与磁棒架连接,磁棒升降滑块固定在磁棒架上,磁棒升降滑块与所述磁棒升降导轨滑动连接。The magnetic rod lifting mechanism comprises a magnetic rod lifting motor, a magnetic rod lifting screw, a magnetic rod lifting screw nut, a magnetic rod lifting slider, a magnetic rod lifting rail, a magnetic rod lifting motor shaft and a magnetic rod lifting screw, and the magnetic rod lifting The screw nut is set on the magnetic rod lifting screw, the magnetic rod lifting screw nut is connected with the magnetic rod frame, the magnetic rod lifting slider is fixed on the magnetic rod frame, and the magnetic rod lifting slider is slidably connected with the magnetic rod lifting rail .
搅拌套驱动机构还包括挡片、位置传感器、轴承,挡片固定在曲柄上,位置传感器固定在曲柄旁边,挡片为薄板,其厚度方向通过位置传感器上的槽,轴承安装于连杆的孔内。The stirring sleeve driving mechanism further comprises a blocking piece, a position sensor and a bearing, the blocking piece is fixed on the crank, the position sensor is fixed beside the crank, the blocking piece is a thin plate, the thickness direction thereof passes through the groove on the position sensor, and the bearing is installed in the hole of the connecting rod Inside.
挡片为直角扇形。The flap is a right-angled fan.
搅拌套驱动机构、磁棒升降机构、托架平移装置、托架升降装置中的滑块与导轨机构均为滚珠直线导轨机构。The slider driving mechanism, the magnetic bar lifting mechanism, the bracket translation device, and the slider and the rail mechanism in the bracket lifting device are both ball linear guide mechanisms.
搅拌套驱动机构的曲柄、连杆为铝合金材质。The crank and connecting rod of the stirring sleeve drive mechanism are made of aluminum alloy.
曲柄与连杆长度比值为小于1:1,搅拌电机频率为0~20Hz。The ratio of the length of the crank to the connecting rod is less than 1:1, and the frequency of the stirring motor is 0-20 Hz.
优选的,曲柄与连杆长度比值为1:4~1:6,搅拌电机频率为2~8Hz。Preferably, the ratio of the length of the crank to the connecting rod is 1:4 to 1:6, and the frequency of the stirring motor is 2 to 8 Hz.
与现有技术相比,本发明的优点在于:The advantages of the present invention over the prior art are:
Figure PCTCN2018090554-appb-000001
本发明的核酸纯化仪,搅拌套驱动机构改用曲柄滑块机构。搅拌电机只需向同一方向连续旋转,不用正反转,就能实现搅拌套的升降与搅拌动作。能量利用率高,系统温升低,振动和噪音小,还彻底消除了搅拌时丝杆、同步带发出的噪音。
Figure PCTCN2018090554-appb-000001
In the nucleic acid purifying apparatus of the present invention, the stirring sleeve driving mechanism is changed to a crank slider mechanism. The stirring motor only needs to rotate continuously in the same direction, and the lifting and stirring action of the stirring sleeve can be realized without positive and negative reversal. High energy utilization, low system temperature rise, low vibration and noise, and completely eliminate the noise generated by the screw and timing belt during mixing.
本发明的仪器振动小,不需要加重底座重量,所以本发明的仪器较传统仪器重量减轻1/2以上,便于搬运。The instrument of the invention has small vibration and does not need to increase the weight of the base, so the instrument of the invention has less than 1/2 weight loss compared with the conventional instrument, and is convenient to carry.
本发明的曲柄滑块机构能驱动搅拌套实现高频率大幅度的搅拌动作,当样本为高粘度或高杂质液体时,提高电机频率,增大搅拌振幅(增大曲柄长度),便能增强搅拌力度,保证特殊样本的核酸纯化质量。The crank slider mechanism of the invention can drive the stirring sleeve to realize a high frequency and a large stirring action, and when the sample is a high viscosity or high impurity liquid, the motor frequency is increased, the stirring amplitude is increased (the crank length is increased), and the stirring can be enhanced. Strength to ensure the quality of nucleic acid purification for specific samples.
本发明的仪器能量利用率高,只需采用常用的小功率电机、曲柄滑块传动机构、及小功率电源,零件成本较低;曲柄滑块机构比丝杆或同步带机构,结构更简单、更经久耐用。The instrument of the invention has high energy utilization rate, and only needs a common low-power motor, a crank-slider transmission mechanism, and a low-power power source, and the component cost is low; the crank slider mechanism is simpler than the screw rod or the timing belt mechanism, More durable.
本发明的曲柄滑块机构中,连杆的两个内孔装有轴承。且搅拌套的移动由滚珠直线导轨机构作为支撑和导向,因此机构中零件之间的相互转动或相互滑动都很顺畅,零件磨损小,仪器使用寿命长。In the crank slider mechanism of the present invention, the two inner holes of the connecting rod are provided with bearings. And the movement of the stirring sleeve is supported and guided by the ball linear guide mechanism, so the mutual rotation or mutual sliding between the parts in the mechanism is smooth, the parts wear is small, and the instrument has a long service life.
尤其在高频率大幅度搅拌时,以上优点更为突出。Especially in the case of high frequency and large agitation, the above advantages are more prominent.
搅拌动作贯穿于整个核酸纯化过程,是对纯化效果影响最大的环节。本发明对搅拌套驱动机构的改进,为提高核酸纯化仪的性能起到关键性作用。The stirring action runs through the entire nucleic acid purification process and is the most influential part of the purification effect. The improvement of the stirring sleeve driving mechanism of the invention plays a key role in improving the performance of the nucleic acid purifying apparatus.
⑵本发明专门设置了托架升降装置。用托架升降装置带动安装在托架装置上的磁棒架和搅拌套架同时升降,保证了磁棒与搅拌套完全同步升降。避免了两个机构配合驱动下,两者不同步时所造成磁珠掉落的风险,显著加强了仪器工作的可靠性。(2) The present invention is specifically provided with a bracket lifting device. The bracket lifting device drives the magnetic rod frame and the stirring sleeve frame mounted on the bracket device to simultaneously lift and lower, thereby ensuring that the magnetic rod and the stirring sleeve are completely synchronized and raised. It avoids the risk of the magnetic beads falling when the two mechanisms are combined and driven, which significantly enhances the reliability of the instrument.
⑶本发明的托架平移装置,代替了现有技术中布置于工作台下方的工作台平移装置。托架平移装置驱动托架装置上的搅拌棒与磁棒一起平移,工作可靠。且整个仪器的动力机构均位于基座后部,仪器使用更安全,布局更紧凑,美观。(3) The carriage translating device of the present invention replaces the table translating device disposed under the table in the prior art. The cradle translating device drives the stir bar on the cradle device to translate with the magnetic bar for reliable operation. And the power mechanism of the whole instrument is located at the back of the base, the instrument is safer to use, the layout is more compact and beautiful.
Figure PCTCN2018090554-appb-000002
本发明的搅拌套驱动机构、磁棒升降机构、托架升降装置、托架平移装置中,均采用滚珠直线导轨机构作为移动部件的支撑与导向机构。导轨与滑块间的滚动摩擦力更小,使磁棒、搅拌套的移动更顺畅,更稳定,工作更可靠。
Figure PCTCN2018090554-appb-000002
In the stirring sleeve driving mechanism, the magnetic rod lifting mechanism, the bracket lifting device, and the bracket translation device of the present invention, the ball linear guide mechanism is used as the supporting and guiding mechanism of the moving member. The rolling friction between the guide rail and the slider is smaller, which makes the movement of the magnetic rod and the stirring sleeve smoother, more stable and more reliable.
本发明提供的核酸纯化仪,改进了搅拌套驱动机构,可以采用低成本的部件,进行高频率大幅度搅拌。能量利用率高,振动小、噪音小、仪器重量轻、结构简单、维修方便、仪器成本低、使用寿命长,且工作更可靠。The nucleic acid purifying instrument provided by the invention improves the stirring sleeve driving mechanism, and can adopt high-cost components to perform high-frequency stirring. High energy utilization, low vibration, low noise, light weight, simple structure, convenient maintenance, low instrument cost, long service life and more reliable work.
附图说明DRAWINGS
图1是核酸纯化仪基本动作示意图;Figure 1 is a schematic diagram of the basic operation of the nucleic acid purifying apparatus;
图2是本发明核酸纯化仪外形图;Figure 2 is an outline view of the nucleic acid purifying apparatus of the present invention;
图3是本发明核酸纯化仪机械部分结构图;Figure 3 is a structural view showing the mechanical part of the nucleic acid purifying apparatus of the present invention;
图4是本发明核酸纯化仪机械部分俯视图;Figure 4 is a plan view showing the mechanical part of the nucleic acid purifying apparatus of the present invention;
图5是本发明核酸纯化仪机械部分右视图;Figure 5 is a right side view of the mechanical portion of the nucleic acid purifying apparatus of the present invention;
图6是本发明核酸纯化仪搅拌套驱动机构立体图;Figure 6 is a perspective view of the driving mechanism of the stirring sleeve of the nucleic acid purifying apparatus of the present invention;
图7是本发明核酸纯化仪搅拌套驱动机构左视图;Figure 7 is a left side view of the stirring sleeve driving mechanism of the nucleic acid purifying apparatus of the present invention;
图8是本发明核酸纯化仪搅拌套驱动机构后视图;Figure 8 is a rear elevational view of the stirring sleeve driving mechanism of the nucleic acid purifying apparatus of the present invention;
图9是本发明核酸纯化仪托架装置立体图。Figure 9 is a perspective view of the carrier device of the nucleic acid purifying apparatus of the present invention.
具体实施方式Detailed ways
以下将结合附图对本发明的构思、具体结构及产生的技术效果作进一步说明,以充分地了解本发明的目的、特征和效果。The concept, the specific structure and the technical effects of the present invention will be further described in conjunction with the accompanying drawings in order to fully understand the objects, features and effects of the invention.
如图2所示,核酸纯化仪由机械部分1、控制系统2、操作单元3、外壳4组成。机械部分1位于核酸纯化仪下部,控制系统2和操作单元3位于上部,外壳4包裹于仪器最外面。机械部分1是核酸纯化仪的核心部件。As shown in FIG. 2, the nucleic acid purifier is composed of a mechanical part 1, a control system 2, an operation unit 3, and a casing 4. The mechanical part 1 is located at the lower part of the nucleic acid purifier, the control system 2 and the operating unit 3 are located at the upper portion, and the outer casing 4 is wrapped around the outermost part of the instrument. Mechanical part 1 is the core component of the nucleic acid purifier.
本发明的核酸纯化仪,搅拌套21的升降及搅拌动作由搅拌套驱动机构5完成。磁棒 20的升降由磁棒升降机构6完成。搅拌套驱动机构5与磁棒升降机构6安装在支撑板12上,组成托架装置9。磁棒20与搅拌套21合体后的升降与平移,分别由托架升降装置8和托架平移装置7驱动托架装置9完成。以上机构与放置深孔板22的工作台14都设置在基座13上。In the nucleic acid purifying apparatus of the present invention, the lifting and stirring operation of the stirring sleeve 21 is performed by the stirring sleeve driving mechanism 5. The lifting and lowering of the magnetic bar 20 is performed by the magnetic bar lifting mechanism 6. The stirring sleeve drive mechanism 5 and the magnetic bar lifting mechanism 6 are mounted on the support plate 12 to constitute the bracket device 9. The lifting and lowering of the magnetic bar 20 after the combination of the stirring sleeve 21 and the stirring sleeve 21 are respectively performed by the carriage lifting device 8 and the carriage translation device 7 to drive the carriage device 9. The above mechanism and the table 14 on which the deep hole plate 22 is placed are disposed on the base 13.
如图3与图9所示,磁棒升降机构6由安装在支撑板12正面上部的磁棒升降电机61驱动,磁棒升降电机61通过磁棒升降电机安装板65固定在支撑板12上。磁棒升降电机61轴带动连接在其下方的磁棒升降丝杆62转动(或磁棒升降丝杆62与磁棒升降电机61轴为一体),磁棒升降丝杆螺母63在磁棒升降丝杆62的驱动下上下移动。磁棒架11与磁棒升降丝杆螺母63固定连接,由磁棒升降丝杆螺母63带动磁棒架11上下移动。磁棒架11与磁棒升降滑块64固定连接,磁棒升降滑块64与安装在支撑板12上的搅拌套导轨55滑动连接,所以磁棒架11沿搅拌套导轨55上下移动,即图9所示的磁棒架11的a动作,a动作的作用是将磁棒20插入和取出搅拌套21。固定在磁棒架11上的薄片66,在移动过程中经过安装于磁棒升降丝杆62一侧的位置传感器57时,将磁棒升降机构6的位置信号传递给控制系统2,控制系统2继而控制磁棒升降电机61,实现对磁棒20升降位移的控制。As shown in FIGS. 3 and 9, the magnetic bar lifting mechanism 6 is driven by a magnetic bar lifting motor 61 mounted on the upper front surface of the support plate 12, and the magnetic bar lifting motor 61 is fixed to the support plate 12 by a magnetic bar lifting motor mounting plate 65. The magnetic rod lifting motor 61 shaft drives the magnetic rod lifting screw 62 connected underneath to rotate (or the magnetic rod lifting screw 62 is integrated with the magnetic rod lifting motor 61 shaft), and the magnetic rod lifting screw nut 63 is in the magnetic rod lifting wire The rod 62 is driven up and down. The magnetic rod frame 11 is fixedly connected to the magnetic rod lifting screw nut 63, and the magnetic rod lifting rod nut 63 drives the magnetic rod holder 11 to move up and down. The magnetic bar frame 11 is fixedly connected to the magnetic bar lifting and lowering slider 64, and the magnetic bar lifting and lowering slider 64 is slidably connected to the stirring sleeve rail 55 mounted on the supporting plate 12, so that the magnetic bar frame 11 moves up and down along the stirring sleeve guide 55, that is, the figure The operation of a of the magnetic rod holder 11 shown in Fig. 9 is a function of inserting and removing the magnetic rod 20 into the stirring sleeve 21. The sheet 66 fixed on the magnetic rod frame 11 transmits the position signal of the magnetic rod lifting mechanism 6 to the control system 2 when passing through the position sensor 57 mounted on the side of the magnetic rod lifting screw 62 during the movement, and the control system 2 The magnetic bar lifting motor 61 is then controlled to control the lifting and lowering of the magnetic bar 20.
磁棒升降丝杆62与磁棒升降丝杆螺母63所组成的丝杆螺母机构,可以为滑动丝杠螺母机构、滚珠丝杠螺母机构、同步带往复运动机构、齿轮齿条机构等其他传动机构。The screw nut mechanism composed of the magnetic rod lifting screw 62 and the magnetic rod lifting screw nut 63 may be a sliding screw nut mechanism, a ball screw nut mechanism, a synchronous belt reciprocating mechanism, a rack and pinion mechanism, and the like. .
如图6、图7、图8所示,搅拌套驱动机构5的动力源为搅拌电机51。搅拌电机51安装在支撑板12的背面下部,搅拌电机51轴从支撑板12的孔中间穿过,曲柄52安装在搅拌电机51轴上,曲柄52位于安装板正面,曲柄52另一端与连杆53一端通过销轴铰接,连杆53另一端与搅拌套架10通过销轴铰接。连杆53上与销轴配合的孔内均安装滚动轴承58,滚动轴承58用于支撑销轴,并减少销轴的磨损。搅拌套架10与搅拌套滑块54固定连接,搅拌套滑块54与搅拌套导轨55滑动连接,所以搅拌电机51通过曲柄滑块机构驱动搅拌套架10沿搅拌套导轨55做升降及搅拌动作,即图6所示的搅拌套21的b和c动作。b和c动作的作用是搅拌套21进入深孔板22的深孔、搅拌磁珠与液体、及退出深孔。在核酸纯化的裂解及清洗阶段,搅拌电机51的轴360度连续旋转,搅拌套架10的振幅,等于两倍的曲柄52的两轴孔之间的长度。在核酸纯化的洗脱阶段,因洗脱液体积较小,搅拌套架10在洗脱阶段的振幅小于裂解及清洗阶段,所以搅拌电机51在洗脱阶段需在一定角度范围内正反转。控制系统2对搅拌电机51正反转的控制信号,来自于安装在曲柄52上的挡片56,和与挡片56配合工作的曲柄52下方的光电位置传感器57。为了便于光电位置传感器57采集搅拌电机51转动的位置信息,挡片56优选为为直角扇形。洗脱阶段的时间约占整 个核酸纯化时间的1/10左右,所以此阶段的电机正反转对核酸纯化仪的噪音影响很小。As shown in FIG. 6, FIG. 7, and FIG. 8, the power source of the stirring sleeve drive mechanism 5 is the stirring motor 51. The agitating motor 51 is mounted on the lower portion of the back surface of the support plate 12, the shaft of the agitating motor 51 passes through the hole of the support plate 12, the crank 52 is mounted on the shaft of the agitating motor 51, the crank 52 is located on the front surface of the mounting plate, and the other end of the crank 52 is connected to the connecting rod One end of the 53 is hinged by a pin, and the other end of the link 53 is hinged to the stirring frame 10 through a pin. A rolling bearing 58 is mounted in the bore of the connecting rod 53 that cooperates with the pin. The rolling bearing 58 serves to support the pin and reduce wear of the pin. The stirring sleeve 10 is fixedly connected with the stirring sleeve slider 54 , and the stirring sleeve slider 54 is slidably connected with the stirring sleeve rail 55 , so the stirring motor 51 drives the stirring sleeve frame 10 to perform lifting and stirring along the stirring sleeve rail 55 through the crank slider mechanism. That is, the b and c of the stirring sleeve 21 shown in Fig. 6 operate. The action of b and c acts to agitate the sleeve 21 into the deep hole of the deep well plate 22, stir the magnetic beads and liquid, and exit the deep hole. In the cracking and washing stage of nucleic acid purification, the shaft of the stirring motor 51 is continuously rotated 360 degrees, and the amplitude of the stirring frame 10 is equal to twice the length between the two shaft holes of the crank 52. In the elution phase of nucleic acid purification, since the volume of the eluate is small, the amplitude of the agitation rack 10 in the elution phase is smaller than that in the pyrolysis and washing stages, so the agitating motor 51 needs to be positively inverted within a certain angle range in the elution phase. The control signal from the control system 2 to the forward and reverse rotation of the agitating motor 51 comes from the flap 56 mounted on the crank 52 and the photoelectric position sensor 57 below the crank 52 that cooperates with the flap 56. In order to facilitate the positional information of the rotation motor 51 by the photoelectric position sensor 57, the flap 56 is preferably a right-angled sector. The elution phase takes about 1/10 of the total nucleic acid purification time, so the motor reversal at this stage has little effect on the noise of the nucleic acid purifier.
搅拌套驱动机构5的曲柄52、连杆53为铝合金材质,可有效减轻运动部件的重量,以减小搅拌套21的惯性力。曲柄52与连杆53长度比值取小于1:1,因连杆53过长会增加连杆53质量,使机构占用的空间较大,连杆53过短则引起搅拌套滑块54的侧压力增加,所以优选曲柄52与连杆53长度比值为1:4~1:6。搅拌电机51的搅拌频率选择为0~20Hz。但根据对各种样本的试验结果,认为搅拌频率在2~8Hz范围内,既能达到最佳搅拌效果,又能节省核酸纯化时间。The crank 52 and the connecting rod 53 of the stirring sleeve drive mechanism 5 are made of aluminum alloy, which can effectively reduce the weight of the moving parts and reduce the inertial force of the stirring sleeve 21. The ratio of the length of the crank 52 to the connecting rod 53 is less than 1:1. Because the connecting rod 53 is too long, the mass of the connecting rod 53 is increased, and the space occupied by the mechanism is large. When the connecting rod 53 is too short, the side pressure of the stirring sleeve slider 54 is caused. Increasing, it is preferable that the ratio of the length of the crank 52 to the link 53 is 1:4 to 1:6. The stirring frequency of the stirring motor 51 is selected to be 0 to 20 Hz. However, according to the test results of various samples, it is considered that the stirring frequency is in the range of 2 to 8 Hz, which can achieve the best stirring effect and save the nucleic acid purification time.
如图9所示,搅拌套驱动机构5与磁棒升降机构6均安装在支撑板12上,搅拌套驱动机构5位于磁棒升降机构6的下方,搅拌套架10位于磁棒架11下方,磁棒架11与搅拌套架10处于工作台14上的深孔板22的正上方。为了安全及美观,安装在支撑板12上的遮挡板16,将位于基座13前部的搅拌套架10和磁棒架11,与后部其他部件隔开。上述磁棒升降机构6、磁棒架11、搅拌套驱动机构5、搅拌套架10、支撑板12、遮挡板16共同组成托架装置9。As shown in FIG. 9, the stirring sleeve driving mechanism 5 and the magnetic bar lifting mechanism 6 are both mounted on the support plate 12, the stirring sleeve driving mechanism 5 is located below the magnetic bar lifting mechanism 6, and the stirring sleeve 10 is located below the magnetic bar frame 11. The magnetic rod frame 11 and the stirring sleeve 10 are located directly above the deep orifice plate 22 on the table 14. For safety and aesthetics, the shutter 16 mounted on the support plate 12 separates the agitator frame 10 and the magnetic bar frame 11 at the front of the base 13 from the other components at the rear. The magnetic bar lifting mechanism 6, the magnetic bar frame 11, the stirring sleeve driving mechanism 5, the stirring jacket 10, the support plate 12, and the shielding plate 16 collectively constitute a bracket device 9.
如图3、图4、图5所示,托架升降装置8由托架升降电机81、托架升降电机安装板82、托架升降丝杆83、托架升降丝杆螺母84、中间支架85、支撑板驱动件86、托架升降滑块87、托架升降导轨88、折弯薄片89构成。托架升降电机81通过托架升降电机安装板82安装于中间支架85上部。托架升降丝杆83与托架升降电机81轴固定连接(或托架升降丝杆83与托架升降电机81轴为一体)。托架升降丝杆螺母84与支撑板驱动件86通过螺栓固定为一体。如图5所示,支撑板驱动件86与托架装置9中的支撑板12侧面贴合后紧固连接。托架升降电机81通过托架升降丝杆83带动托架升降丝杆螺母84上下移动,托架升降丝杆螺母84继而通过支撑板12带动托架装置9上下移动。在托架装置9的支撑板12正面安装托架升降滑块87,托架升降滑块87与紧固在中间支架85上的托架升降导轨88形成上下方向滑动连接,使托架装置9能够稳定顺畅地上下移动,在托架装置9升降过程中,磁棒20为插入搅拌套21底部的状态,磁棒20与搅拌套21合体的上下移动,即如图3所示的e动作,e动作将磁珠吸出和放入深孔板22的深孔中。固定在支撑板驱动件86上的折弯薄片89,经过固定于于中间支架85的光电位置传感器57时,将位置信号传递给控制系统2,控制系统2继而控制托架升降电机81。本发明增设的托架升降装置8,实现了磁棒20与搅拌套21合体(磁棒20插入搅拌套21底部)后一起上下移动,由托架升降电机81独立驱动,位移便于控制,且移动磁珠的过程安全可靠。As shown in FIG. 3, FIG. 4 and FIG. 5, the bracket lifting device 8 is composed of a bracket lifting motor 81, a bracket lifting motor mounting plate 82, a bracket lifting screw 83, a bracket lifting screw nut 84, and an intermediate bracket 85. The support plate drive member 86, the bracket lifting slider 87, the bracket lifting rail 88, and the bent sheet 89 are formed. The carriage lift motor 81 is attached to the upper portion of the intermediate bracket 85 via the bracket lift motor mounting plate 82. The bracket lifting screw 83 is fixedly coupled to the bracket lifting motor 81 (or the bracket lifting screw 83 is integrated with the bracket lifting motor 81 shaft). The bracket lift screw nut 84 and the support plate drive member 86 are integrally fixed by bolts. As shown in FIG. 5, the support plate driving member 86 is fastened to the side of the support plate 12 in the bracket device 9, and is fastened. The carriage lifting motor 81 drives the carriage lifting screw nut 84 up and down by the carrier lifting screw 83, and the carrier lifting screw nut 84 then drives the carriage device 9 up and down through the support plate 12. A bracket lifting slider 87 is attached to the front surface of the support plate 12 of the bracket device 9, and the bracket lifting slider 87 is slidably coupled to the bracket lifting rail 88 fastened to the intermediate bracket 85 so that the bracket device 9 can be Stabilizing smoothly up and down, during the lifting process of the bracket device 9, the magnetic bar 20 is inserted into the bottom of the stirring sleeve 21, and the magnetic bar 20 and the stirring sleeve 21 are moved up and down, that is, the e action shown in FIG. The action sucks the magnetic beads into and into the deep holes of the deep well plate 22. The bent sheet 89 fixed to the support plate driving member 86 transmits a position signal to the control system 2 via the photoelectric position sensor 57 fixed to the intermediate holder 85, which in turn controls the carriage lifting motor 81. The bracket lifting device 8 of the present invention realizes that the magnetic bar 20 and the stirring sleeve 21 are combined (the magnetic rod 20 is inserted into the bottom of the stirring sleeve 21), and then moved up and down together, and the bracket lifting motor 81 is independently driven, the displacement is convenient to control, and the movement is performed. The process of magnetic beads is safe and reliable.
托架升降丝杆83与托架升降丝杆螺母84组成的丝杆螺母机构,可以为滑动丝杠螺 母机构、滚珠丝杠螺母机构、同步带往复运动机构、齿轮齿条机构等其他传动机构。The screw nut mechanism composed of the bracket lifting screw 83 and the bracket lifting screw nut 84 may be a sliding screw nut mechanism, a ball screw nut mechanism, a timing belt reciprocating mechanism, a rack and pinion mechanism, and the like.
如图3所示,托架平移装置7的动力源为托架平移电机71。托架平移电机71通过托架平移电机安装板72固定在基座13上,托架平移电机71带动托架平移丝杆73旋转,托架平移丝杆73带动托架平移丝杆螺母74水平方向移动。驱动弯板75的一面与托架平移丝杆螺母74固定连接,折弯的另一面与托架升降机构中的中间支架85用螺栓固定连接。托架平移滑块76安装在中间支架85上,托架平移导轨77固定在基座13上。托架平移滑块76与托架平移导轨77水平方向滑动连接,托架平移丝杆螺母74通过驱动弯板75带动中间支架85沿托架平移导轨77水平移动。此时,中间支架85所在的托架升降装置8与托架装置9在水平方向无相对移动,两者为一个整体。所以驱动弯板75带动了托架装置9水平移动,托架装置9水平移动过程中磁棒20为插入搅拌套21底部的状态,以上磁棒20与搅拌套21合体的水平移动即图3所示的d动作。d动作与上述a、和e动作配合完成磁珠的搬运工作。托架装置9的水平移动因托架平移滑块76与托架平移导轨77的设置而更流畅。固定在驱动弯板75上的折弯薄片二78与光电位置传感器57配合,实现托架装置9水平移动的位置信号传输。As shown in FIG. 3, the power source of the carriage translating device 7 is a carriage translation motor 71. The carriage translation motor 71 is fixed on the base 13 by the bracket translation motor mounting plate 72. The carriage translation motor 71 drives the carriage translation screw 73 to rotate, and the carriage translation screw 73 drives the carriage to translate the screw nut 74 horizontally. mobile. One side of the drive bending plate 75 is fixedly coupled to the bracket translation screw nut 74, and the other side of the bending is bolted to the intermediate bracket 85 in the bracket lifting mechanism. The carriage translation slider 76 is mounted on the intermediate bracket 85, and the carriage translation guide 77 is fixed to the base 13. The carriage translation slider 76 is slidably coupled to the carriage translation rail 77 in a horizontal direction, and the carriage translation screw nut 74 drives the intermediate bracket 85 to horizontally move along the carriage translation guide 77 by the drive bending plate 75. At this time, the carriage lifting device 8 where the intermediate bracket 85 is located and the bracket device 9 are not moved in the horizontal direction, and the two are integrated. Therefore, the driving curved plate 75 drives the bracket device 9 to move horizontally. During the horizontal movement of the bracket device 9, the magnetic bar 20 is inserted into the bottom of the stirring sleeve 21, and the horizontal movement of the magnetic bar 20 and the stirring sleeve 21 is the same as that of FIG. The d action shown. The d action cooperates with the a and e actions described above to complete the handling of the magnetic beads. The horizontal movement of the carriage device 9 is smoother due to the arrangement of the carriage translation slider 76 and the carriage translation guide 77. The bent sheet 2 78 fixed to the drive bending plate 75 cooperates with the photoelectric position sensor 57 to realize position signal transmission of the horizontal movement of the carriage device 9.
托架平移丝杆73与托架平移丝杆螺母74所组成的丝杆螺母机构,可以为滑动丝杠螺母机构、滚珠丝杠螺母机构、同步带往复运动机构、齿轮齿条机构等其他传动机构。The screw nut mechanism composed of the bracket translation screw 73 and the bracket translation screw nut 74 may be a sliding screw nut mechanism, a ball screw nut mechanism, a timing belt reciprocating mechanism, a rack and pinion mechanism, and the like. .
进一步说明,在磁棒20未插入搅拌套21的状态下,托架升降装置8和托架平移装置7同样可以驱动托架装置9进行升降和平移,完成核酸纯化过程的一些辅助性动作。Further, in a state where the magnetic bar 20 is not inserted into the agitating sleeve 21, the cradle lifting device 8 and the cradle translating device 7 can also drive the cradle device 9 to perform lifting and translation to complete some auxiliary actions of the nucleic acid purification process.
搅拌套驱动机构5、磁棒升降机构6、托架平移装置7、托架升降装置8中的滑块与导轨机构均为滚动直线导轨机构,导轨与滑块之间的摩擦力为滚动摩擦力,阻力更小,运动件的运动更顺畅、平稳。The slider and the rail mechanism in the stirring sleeve driving mechanism 5, the magnetic rod lifting mechanism 6, the bracket translation device 7, and the bracket lifting device 8 are rolling linear guide mechanisms, and the friction between the guide rail and the slider is rolling friction The resistance is smaller and the movement of the moving parts is smoother and smoother.
综上所述,托架装置9中的磁棒升降机构6实现磁棒20单独升降的动作(a动作),将磁棒20插入或取出搅拌套21。托架升降装置8和托架平移装置7分别实现磁棒20与搅拌套21合体后的上下移动和平移动作(d动作和e动作),以上a、d、e动作结合完成磁珠的搬运工作。搅拌套驱动机构5能带动搅拌套21单独上下移动及进行搅拌(b动作和c动作),完成搅拌套21进出深孔并对深孔中磁珠与液体的搅拌工作。控制系统2根据光电位置传感器57的信号,有序地控制各电机动作,完成核酸纯化过程。As described above, the magnetic bar lifting and lowering mechanism 6 in the cradle device 9 realizes an operation (a operation) in which the magnetic bar 20 is separately raised and lowered, and the magnetic bar 20 is inserted or taken out of the agitating sleeve 21. The bracket lifting device 8 and the bracket translation device 7 respectively realize the up and down movement and translation movement (d action and e action) after the magnetic bar 20 and the stirring sleeve 21 are combined, and the a, d, and e actions are combined to complete the magnetic bead handling work. . The stirring sleeve driving mechanism 5 can drive the stirring sleeve 21 to move up and down separately and perform stirring (b action and c action), and complete the mixing operation of the stirring sleeve 21 into and out of the deep hole and the magnetic beads and the liquid in the deep hole. The control system 2 sequentially controls the operation of each motor based on the signal of the photoelectric position sensor 57 to complete the nucleic acid purification process.
搅拌套驱动机构5、磁棒升降机构6、托架平移装置7、托架升降装置8为四个可独立控制及动作的部件,可以通过改变控制系统的程序,完成各种动作及动作顺序的组合,实现核酸纯化过程,以满足使用者的个性化需求。The stirring sleeve driving mechanism 5, the magnetic rod lifting mechanism 6, the bracket translation device 7, and the bracket lifting device 8 are four independently controllable and movable components, and can complete various actions and action sequences by changing the program of the control system. Combine to realize the nucleic acid purification process to meet the individual needs of users.
尽管上面已经示出和描述了本发明的多个实施方式,对于本领域的普通技术人员而言,可以理解在不脱离本发明的原理和精神的情况下对这些实施方式进行多种变化、修改、替换和变型,本发明的保护范围由各项权利要求及其等同范围限定。While various embodiments of the present invention have been shown and described, it will be understood by those skilled in the art The scope of the invention is defined by the claims and their equivalents.

Claims (10)

  1. 一种核酸纯化仪,包括机械部分(1)、控制系统(2)、操作单元(3)、外壳(4),所述机械部分(1)位于核酸纯化仪下部,所述控制系统(2)和所述操作单元(3)位于仪器上部,所述外壳(4)包裹于仪器最外面,所述机械部分(1)包括搅拌套驱动机构(5)、搅拌套架(10)、磁棒升降机构(6)、磁棒架(11)、支架或支撑板(12)、基座(13)、工作台(14)、工作台平移装置或支架平移装置,所述搅拌套架(10)安装于所述搅拌套驱动机构(5)上,所述磁棒架(11)安装于所述磁棒升降机构(6)上,所述搅拌套驱动机构(5)与所述磁棒升降机构(6)安装于支架或支撑板(12)上,支架或支撑板(12)与所述工作台(14)安装于所述基座(13)上,所述工作台(14)设置于所述磁棒架(11)和所述搅拌套架(10)下方;A nucleic acid purifying apparatus comprising a mechanical part (1), a control system (2), an operating unit (3), a casing (4), the mechanical part (1) is located in a lower part of the nucleic acid purifying apparatus, and the control system (2) And the operating unit (3) is located at the upper part of the instrument, the outer casing (4) is wrapped around the outermost part of the instrument, and the mechanical part (1) comprises a stirring sleeve driving mechanism (5), a stirring sleeve (10), a magnetic rod lifting Mechanism (6), magnetic rod frame (11), bracket or support plate (12), base (13), table (14), table translation device or bracket translation device, said stirring frame (10) is installed On the stirring sleeve driving mechanism (5), the magnetic rod frame (11) is mounted on the magnetic rod lifting mechanism (6), the stirring sleeve driving mechanism (5) and the magnetic rod lifting mechanism ( 6) mounted on a bracket or support plate (12), the bracket or support plate (12) and the work table (14) are mounted on the base (13), the work table (14) is disposed on the a magnetic bar frame (11) and the stirring frame (10) below;
    其特征在于,It is characterized in that
    所述搅拌套驱动机构(5)包括搅拌电机(51)、曲柄(52)、连杆(53)、搅拌套滑块(54)、搅拌套导轨(55),所述搅拌电机(51)轴与所述曲柄(52)固定连接,所述曲柄(52)与所述连杆(53)一端可转动连接,所述连杆(53)另一端与所述搅拌套滑块(54)可转动连接,所述搅拌套架(10)固定在所述搅拌套滑块(54)上,所述搅拌套滑块(54)与所述搅拌套导轨(55)滑动连接。The stirring sleeve driving mechanism (5) comprises a stirring motor (51), a crank (52), a connecting rod (53), a stirring sleeve slider (54), a stirring sleeve rail (55), and the stirring motor (51) shaft Fixedly connected to the crank (52), the crank (52) is rotatably connected to one end of the connecting rod (53), and the other end of the connecting rod (53) is rotatable with the stirring sleeve slider (54) Connected, the stirring sleeve (10) is fixed on the stirring sleeve slider (54), and the stirring sleeve slider (54) is slidably connected with the stirring sleeve rail (55).
  2. 根据权利要求1所述的核酸纯化仪,其特征在于,还包括托架升降装置(8),所述托架升降装置(8)包括托架升降电机(81)、中间支架(85)、托架升降丝杆(83)、托架升降丝杆螺母(84)、托架升降滑块(87)、托架升降导轨(88),所述托架升降电机(81)安装于所述中间支架(85)上,所述托架升降丝杆(83)与所述托架升降电机(81)轴连接,所述托架升降丝杆螺母(84)套装于所述托架升降丝杆(83)上,所述托架升降丝杆螺母(84)与所述支撑板(12)连接,所述托架升降滑块(87)安装在所述支撑板(12)上,所述托架升降导轨(88)固定在所述中间支架(85)上,所述托架升降滑块(87)与所述托架升降导轨(88)滑动连接。The nucleic acid purifying apparatus according to claim 1, further comprising a cradle lifting device (8) comprising a cradle lifting motor (81), an intermediate bracket (85), and a holder a lifting screw (83), a bracket lifting screw nut (84), a bracket lifting slider (87), a bracket lifting rail (88), and the bracket lifting motor (81) is mounted on the intermediate bracket (85) The bracket lifting screw (83) is pivotally coupled to the bracket lifting motor (81), and the bracket lifting screw nut (84) is fitted to the bracket lifting screw (83) The bracket lifting screw nut (84) is coupled to the support plate (12), and the bracket lifting slider (87) is mounted on the support plate (12) A rail (88) is fixed to the intermediate bracket (85), and the bracket lifting slider (87) is slidably coupled to the bracket lifting rail (88).
  3. 根据权利要求2所述的核酸纯化仪,其特征在于,所述支架平移装置为托架平移装置(7),所述托架平移装置(7)包括托架平移电机(71)、托架平移丝杆(73)、托架平移丝杆螺母(74)、托架平移滑块(76)、托架平移导轨(77),所述托架平移电机(71)安装于所述基座(13)上,所述托架平移丝杆(73)与所述托架平移电机(71)轴连接,所述托架平移丝杆螺母(74)套装于所述托架平移丝杆(73)上,所述托架平移丝杆螺母(74)与所述托架升降装置(8)连接,所述托架平移滑块(76)安装在所述托架升降装置(8)上,所述托架平移导轨(77)安装在所述基座(13)上,所述托架平移滑块(76)与所述托架平移 导轨(77)滑动连接。The nucleic acid purifying apparatus according to claim 2, wherein said holder translation means is a carriage translation means (7), said carriage translation means (7) comprising a carriage translation motor (71), carriage translation a lead screw (73), a carriage translation screw nut (74), a carriage translation slider (76), a carriage translation guide rail (77), and the bracket translation motor (71) is mounted to the base (13) The bracket translation screw (73) is pivotally coupled to the carriage translation motor (71), and the carriage translation screw nut (74) is fitted over the carriage translation screw (73) The bracket translation screw nut (74) is coupled to the bracket lifting device (8), and the bracket translation slider (76) is mounted on the bracket lifting device (8) A carriage translation rail (77) is mounted on the base (13), the bracket translation slider (76) being slidably coupled to the carriage translation rail (77).
  4. 根据权利要求1所述的核酸纯化仪,其特征在于,所述磁棒升降机构(6)包括磁棒升降电机(61)、磁棒升降丝杆(62)、磁棒升降丝杆螺母(63)、磁棒升降滑块(64)、磁棒升降导轨,所述磁棒升降电机(61)轴与所述磁棒升降丝杆(62)连接,所述磁棒升降丝杆螺母(63)套装于所述磁棒升降丝杆(62)上,所述磁棒升降丝杆螺母(63)与所述磁棒架(11)连接,所述磁棒升降滑块(64)固定在所述磁棒架(11)上,所述磁棒升降滑块(64)与所述磁棒升降导轨滑动连接。The nucleic acid purifying apparatus according to claim 1, wherein said magnetic bar lifting mechanism (6) comprises a magnetic bar lifting motor (61), a magnetic bar lifting screw (62), and a magnetic bar lifting screw nut (63). a magnetic bar lifting slider (64), a magnetic bar lifting rail, the magnetic bar lifting motor (61) shaft is connected to the magnetic bar lifting screw (62), the magnetic bar lifting screw nut (63) Suited on the magnetic bar lifting screw (62), the magnetic bar lifting screw nut (63) is connected to the magnetic bar frame (11), and the magnetic bar lifting slider (64) is fixed on the On the magnetic bar frame (11), the magnetic bar lifting slider (64) is slidably coupled to the magnetic bar lifting rail.
  5. 根据权利要求1所述的核酸纯化仪,其特征在于,所述搅拌套驱动机构(5)还包括挡片(56)、位置传感器(57)、轴承(58),所述挡片(56)固定在曲柄(52)上,所述位置传感器(57)固定在所述曲柄(52)旁边,所述挡片(56)为薄板,其厚度方向通过所述位置传感器(57)上的槽,所述轴承(58)安装于所述连杆(53)的孔内。The nucleic acid purifying apparatus according to claim 1, wherein the stirring sleeve driving mechanism (5) further comprises a flap (56), a position sensor (57), a bearing (58), and the flap (56) Fixed to the crank (52), the position sensor (57) is fixed beside the crank (52), the baffle (56) is a thin plate, the thickness direction of which passes through the slot on the position sensor (57), The bearing (58) is mounted within the bore of the connecting rod (53).
  6. 根据权利要求5所述的核酸纯化仪,其特征在于,所述挡片(56)为直角扇形。The nucleic acid purifier according to claim 5, wherein the flap (56) has a right-angled sector shape.
  7. 根据权利要求1-4中任一权利要求所述的核酸纯化仪,其特征在于,滑块与导轨机构均为滚珠直线导轨机构。The nucleic acid purifying apparatus according to any one of claims 1 to 4, wherein the slider and the rail mechanism are both ball linear guide mechanisms.
  8. 根据权利要求1所述的核酸纯化仪,其特征在于,所述搅拌套驱动机构(5)的所述曲柄(52)、所述连杆(53)为铝合金材质。The nucleic acid purifying apparatus according to claim 1, wherein the crank (52) and the link (53) of the stirring sleeve driving mechanism (5) are made of an aluminum alloy.
  9. 根据权利要求1所述的核酸纯化仪,其特征在于,所述曲柄(52)与所述连杆(53)长度比值小于1:1,所述搅拌电机(51)频率为0~20Hz。The nucleic acid purifying apparatus according to claim 1, wherein a ratio of a length of the crank (52) to the connecting rod (53) is less than 1:1, and a frequency of the stirring motor (51) is 0 to 20 Hz.
  10. 根据权利要求1所述的核酸纯化仪,其特征在于,所述曲柄(52)与所述连杆(53)长度比值为1:4~1:6,所述搅拌电机(51)频率为2~8Hz。The nucleic acid purifying apparatus according to claim 1, wherein a ratio of a length of the crank (52) to the connecting rod (53) is 1:4 to 1:6, and a frequency of the stirring motor (51) is 2. ~8Hz.
PCT/CN2018/090554 2017-07-13 2018-06-11 Nucleic acid purifier WO2019011088A1 (en)

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