WO2020034143A1 - Dispositif de poignée, dispositif de positionnement, dispositif de chargement et séquenceur de gènes - Google Patents

Dispositif de poignée, dispositif de positionnement, dispositif de chargement et séquenceur de gènes Download PDF

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Publication number
WO2020034143A1
WO2020034143A1 PCT/CN2018/100817 CN2018100817W WO2020034143A1 WO 2020034143 A1 WO2020034143 A1 WO 2020034143A1 CN 2018100817 W CN2018100817 W CN 2018100817W WO 2020034143 A1 WO2020034143 A1 WO 2020034143A1
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WO
WIPO (PCT)
Prior art keywords
bare chip
chip
handle device
groove
positioning
Prior art date
Application number
PCT/CN2018/100817
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English (en)
Chinese (zh)
Inventor
胡壮洪
倪鸣
魏栋
陈�峰
Original Assignee
深圳华大智造科技有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 深圳华大智造科技有限公司 filed Critical 深圳华大智造科技有限公司
Priority to PCT/CN2018/100817 priority Critical patent/WO2020034143A1/fr
Priority to CN201880005914.3A priority patent/CN112955536B/zh
Publication of WO2020034143A1 publication Critical patent/WO2020034143A1/fr

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6869Methods for sequencing

Definitions

  • the invention relates to the technical field of gene sequencing equipment, in particular to a handle device for a sequencing chip and a positioning device thereof, and a gene sequencer.
  • the second-generation sequencing technology is based on the development of the first-generation Sanger sequencing technology and has the characteristics of low cost, high throughput, and automation. It is applied to whole genome sequencing, transcriptome sequencing, and metagenomic sequencing. The low cost and high throughput are An important direction for its future development.
  • the current sequencing chip is usually used after the entire 8-inch chip is subjected to secondary cutting and special process packaging. The raw materials are wasted, and the sequencing area of the chip cannot be maximized. The chip needs to be cut and packaged. Increasing the production process of the chip, and at the same time each package requires auxiliary materials such as cover glass, which is costly, and the gap between the cover glass and the chip is usually controlled at the micron or even nanometer level.
  • the consistency of the thickness of the sealed cavity formed is difficult to control and affects Efficiency and effect of fluid loading; not only that, the chip can only be positioned by the chip itself during chip transportation and information collection, which is easy to damage the chip. Therefore, there is a need to develop a sequencing system and auxiliary equipment that indirectly carry bare chips for gene molecule loading, reagent synthesis, and information collection.
  • the technical solution provided by the present invention is: a handle device for assisting a bare chip to perform a biochemical reaction, a chip slot is provided in the middle of the device to install the bare chip, and a sealing slot is provided inside the chip slot to fixedly connect the chip slot
  • a vacuum groove is provided on the inner side of the sealing groove, and the vacuum groove is communicated with the outside to adsorb the bare chip with a negative pressure.
  • a positioning groove is provided on the side of the chip groove for positioning during the transportation process.
  • reaction surface and edge of the bare chip do not touch the reagent tank.
  • the outside of the chip slot is a clamping portion and a limiting portion, and a middle portion of the limiting portion extends out of the positioning portion toward the chip slot.
  • the clamping portion, the limiting portion, and the positioning The part is engaged with the bare chip.
  • a plurality of conductive internal channels are opened between the clamping portion and the vacuum tank.
  • a plurality of conductive internal channels are opened between the limiting portion and the vacuum tank.
  • the handle device opens a plurality of conductive internal channels between an outer side wall between the limiting portion and the vacuum tank and the vacuum tank.
  • sealing groove is adhesively connected to the bare chip.
  • clamping portion is provided with a plurality of mounting holes for mounting to other equipment.
  • the invention also provides a positioning device for assembling and positioning the handle device and a bare chip, including a base, and a plurality of convex portions, sliders and fastening portions provided on the base, wherein the slider is located Above the side of the clamping portion, the convex portion and the fastening portion are enclosed outside the chip groove and the stopper portion, and the convex portion and the slider that are in contact with the stopper portion An end protrusion surrounds the outside of the bare chip.
  • each of the fastening portions includes a fastener and penetrates from the inside of the fastener and abuts the side wall of the handle device
  • the pin is threadedly assembled with the pin.
  • the sliders are respectively provided with limiting blocks on both sides of the moving direction to restrain the displacement of the slider, and a slide groove is provided on the base for installing a slide rail that cooperates with the slider.
  • the present invention also provides a loading device for loading gene molecules on the surface of a bare chip.
  • the device includes a bottom plate and a cover plate, and a groove is provided on the bottom plate to fix the handle device with a negative pressure on the bare chip.
  • the bottom surface of the cover plate facing the bare chip is provided with a second sealing groove and a flow channel groove, the second sealing groove is bonded to the bare chip to form a cavity, and the flow channel groove or the second sealing groove is opened for liquid inlet. And outlet.
  • each of the second sealing grooves is fan-shaped and encloses a circle; the flow channel groove is located inside the edge of the second sealing groove.
  • an adhesive is fixed on the edge of the second sealing groove, and the adhesive is adhered to the bare chip.
  • the invention further provides a gene sequencer, comprising a manipulator, a liquid exchange system, a bare chip, and the handle device carrying the bare chip.
  • the manipulator is connected to the clamping portion for transporting the bare chip into Biochemical reactions are performed in several reagent tanks of the liquid exchange system.
  • the top of each reagent tank is open, and the side wall is provided with an extension that cooperates with the positioning tank for the handle device, the bare Chip limit.
  • the bottom of the reagent tank and a side wall remote from the handle device are not in contact with the bare chip.
  • the present invention provides a handle device for assisting a bare chip to perform a biochemical reaction.
  • a chip slot is provided in the middle of the device to install the bare chip, and a sealing slot is provided inside the chip slot to fix Connect the bare chip, a vacuum groove is opened inside the sealed groove, the vacuum groove is communicated with the outside to suck the bare chip with negative pressure, and a positioning groove is provided at the side of the chip groove for positioning during the transportation process.
  • the handle device can be used in a gene sequencing system with a bare chip, which has a high repetition rate, improves the utilization rate of the sequencing area, and reduces material and manufacturing costs.
  • the assembly relationship between each bare chip and the handle device is highly repeatable and reproducible, and the coordination relationship is good.
  • gene molecules can be directly loaded on each bare chip. Applied to the gene sequencer, on the one hand, the sequencing throughput is large and the sequencing accuracy is high; on the other hand, the operation is convenient, the degree of automation is high, and the test efficiency is good.
  • FIG. 1 is a schematic structural diagram of a part of a gene sequencer of the present invention.
  • FIG. 2 is a schematic diagram of the handle device shown in FIG. 1.
  • Fig. 3 is a sectional view of the handle device shown in Fig. 2 at the IV-IV position.
  • FIG. 4 is a combined view of a positioning device, a handle device, and a bare chip according to the present invention.
  • FIG. 5 is an exploded view of the overall structure shown in FIG. 4.
  • FIG. 6 is an assembly diagram of a loading device, a handle device, and a bare chip according to an embodiment of the present invention.
  • FIG. 7 is a schematic view of the structure shown in FIG. 6 from another angle.
  • FIG. 8 is a schematic structural diagram of a reagent tank shown in FIG. 1.
  • Handle device 100 Chip slot 110 the seal groove 120 Vacuum tank 130 Positioning slot 170 Clamping section 150 Limiting Department 140 aisle 160 Mounting holes 151 Positioning Department 141 Positioning means 200 Base 220 Convex 221 Slider 210 Fastening section 225 Raised 211 fastener 2252
  • the second-generation sequencing technology is currently a powerful tool for analyzing the evolution and classification of organisms, studying cancer-related autism and other disease-related genes, and conducting in vitro diagnostics, which has promoted a better understanding of life sciences and also promoted the development of the health industry .
  • the second-generation sequencing technology has become relatively mature, and new sequencing platforms and products have also changed from generation to generation, and are rapidly developing towards the trend of low cost and high throughput. Therefore, the present invention designs an 8-inch sequencing chip (hereinafter referred to as a bare chip 300) loaded with gene molecules (such as DNA nanospheres) on a handle for sequencing, which greatly reduces the sequencing cost and greatly improves the sequencing throughput.
  • FIG. 1 shows a part of a gene sequencer 500, which is an immersion sequencing system, including a robotic hand 510, a liquid exchange system, a bare chip 300, and a handle device 100, wherein the bare chip 300 is carried by the handle device 100,
  • the manipulator 510 grips the upper end of the handle device 100, and the manipulator 510 can move up, down, left, and right to transport the bare chip 300 into the reagent tanks 520 of different liquid exchange systems for biochemical reactions.
  • the sequencing chip is an indispensable element in the test.
  • the second-generation sequencing technology includes the process of loading genetic molecules on the sequencing chip, and then pairing, labeling, and collecting information on the bases of the molecules one by one. Complete genetic sequence information. Therefore, the main use process of the bare chip 300 in this article includes:
  • the handle device 100 of the present invention will be described in detail below with reference to FIGS. 2 and 3.
  • the handle device 100 as shown in FIG. 2 (omitting the middle length section), has a long shape, and the bare chip 300 to be carried is circular, of which:
  • the chip slot 110 is opened in the middle section of the handle device 100 and is used to install the bare chip 300;
  • the sealing groove 120 is opened inside the chip groove 110 and is used to fixedly connect the bare chip 300, such as an adhesive connection;
  • a vacuum tank 130 is opened inside the sealing tank 120, and the vacuum tank 130 is electrically connected to the outside, and is used to adsorb the bare chip 300 by negative pressure;
  • the positioning groove 170 is provided on the side of the chip groove 110 in the longitudinal direction, so as to prevent the bare chip 300 and the reagent groove 520 from touching.
  • the chip groove 110 matches the contour of the bare chip 300 and has the same thickness. After assembly, the surface to be loaded of the bare chip 300 is flush with the end surface of the handle device 100; and The outline of the sealing groove 120 and the vacuum groove 130 is a rectangular frame, and the distance between corresponding sides is the same. The depth and width of the sealing groove 120 are smaller than the depth and width of the vacuum groove 130.
  • the positioning groove 170 is a strip-shaped groove on the side of the chip slot 110, and the strip-shaped groove extends to the rear end of the handle device 100 to form a planar slide groove communicating with the outside. The depth of the positioning groove 170 is greater than The depth of the vacuum groove 130 and the width of the positioning groove 170 are greater than the width of the vacuum groove 130. It can be understood that the shapes and sizes of the sealing grooves 120 and the vacuum grooves 130 are not limited to this embodiment, and the shapes and sizes of the positioning grooves 170 are designed according to actual needs, and details are not described herein.
  • the handle device 100 can be gripped by auxiliary equipment (such as a robot hand 510) and has a partial positioning function.
  • the chip slot 110 has a clamping portion 150 and a limiting portion 140 on the outer side, respectively.
  • a positioning portion 141 extends from a middle portion of the bit portion 140 toward the chip slot 110.
  • the clamping portion 150, the limiting portion 140, and the positioning portion 141 are engaged with the bare chip 300.
  • a plurality of conductive internal channels 160 are defined between the clamping portion 150 and the vacuum tank 130.
  • the clamping portion 150 is provided with a plurality of mounting holes 151 for mounting to other equipment.
  • the sealing groove 120 is adhesively connected to the bare chip 300; the glue may not be adhered to the silicon chip, and acts as a flexible or elastic sealing material and is squeezed on the back of the bare chip 300 to facilitate the bare chip. Reuse of 300 helps reduce material costs.
  • the positioning portion 141 is an arcuate shape (refers to a long arc segment including a circle center, where the arc angle is greater than 180 °), and protrudes from the middle portion of the limiting portion 140 toward the chip slot 110.
  • the end of the junction is recessed toward the inside of the limiting portion 140 for holding the bare chip 300.
  • the surface of the chip groove 110 is a cross-sectional direction, and the channel 160 approaches the vacuum groove 130
  • the corner region of the clamping portion 150 opens vertically downward, and then is laterally conducted to the side of the clamping portion 150 (as shown in FIG. 3), and the channel 160 has a circular cross section (as shown in FIG. 2).
  • the relative relationship between the positioning portion 141 and the limiting portion 140 is not limited to this embodiment, and the shape and size of the positioning portion are designed according to actual needs, and may be a square or a triangle.
  • the channel 160 may be formed between the vacuum groove 130 and the limiting portion 140, or from any position on an outer side wall between the limiting portion 140 and the clamping portion 150.
  • the external side wall When the handle device 100 is placed on top of the chip slot 110 and placed horizontally, the external side wall includes a bottom wall and two vertical side walls. When the handle device 100 is held vertically, the external side wall includes a distance from The back wall of the chip slot 110 and the two vertical side walls, so that the position of the channel 160 is not limited to this embodiment.
  • connection principle of the handle device 100 and the bare chip 300 is: dispensing is performed in the sealing groove 120, the bare chip 300 is correctly assembled, and fixed for a period of time in a negative pressure adsorption manner, so that the handle device 100 It is attached to the bare chip 300, sealed, and does not fall, which is enough to complete the subsequent reactions and the transportation of the operation process.
  • the bonding can be adhesion or compaction, and the transportation process can always be performed in the form of negative pressure adsorption.
  • the positioning device 200 of the present invention will be described in detail below with reference to FIGS. 4 and 5.
  • the positioning device 200 includes a base 220 and a plurality of convex portions 221, a slider 210 and a fastening portion 225 provided on the base 220.
  • the slider 210 is located above the side of the clamping portion 150, and the convex portion 221 and the fastening portion 225 are enclosed outside the chip groove 110 and the limiting portion 140, and the limiting portion
  • the convex portion 221 contacted by the portion 140 and the protrusion 211 at the end of the slider 210 are surrounded by the outside of the bare chip 300.
  • the fastening portions 225 are disposed outside the same side wall of the handle device 100, and each of the fastening portions 225 includes a fastener 2252 and penetrates from the inside of the fastener 2252 and abuts the handle device 100ach side pin 2251.
  • the fastener 2252 is fixedly installed on the base 220, the pin 2251 is threaded, and is screwed in the threaded hole of the fastener 2252. After the handle device 100 is placed, the pin 2251 is locked so that one end thereof squeezes the handle device 100 , The handle device 100 can be fixed.
  • Limit blocks (222, 223) are respectively provided on both sides of the slider 210 in the moving direction to restrict the displacement of the slider 210, and a slide groove is provided on the base 220 for installation and connection with the slider. 210 cooperates with the slide rail 224.
  • the convex portion 221 is a cylinder and is provided with three, two of which are provided at the end of the same side of the handle device 100, especially one side of the chip slot 110. At the end, the height of the two protrusions 221 is not greater than the thickness of the handle device 100 (the vertical distance between the surface of the chip slot 110 and the bottom surface of the handle device 100). Another one of the convex portions 221 is provided outside the midpoint of the limiting portion 140. In this embodiment, the height of the convex portion 221 is higher than the thickness of the handle device 100, and three of the convex portions 221 are formed. Three positioning points that are not in a straight line can position the handle device 100. It can be understood that the number and shape of the convex portions 221 are not limited to this embodiment, and details are not described herein.
  • the fastening portion 225 is provided on the opposite side of the convex portion 221, that is, the other side of the chip groove 110. Two fastening portions are provided, each of which is fastened.
  • the portion 225 is provided with a fastener 2252 and a pin 2251.
  • the fastener 2252 is provided with two holes perpendicular to the direction of the chip slot 110, and the interior of the fastener 2252 is opened parallel to the direction of the chip slot 110.
  • the 1 horizontal through hole is provided between 2 vertical holes, and the horizontal through hole is provided with a thread for inserting a pin 2251 to abut the side wall of the handle device 100, and the vertical hole is used for
  • the fastener 2252 is locked with the base 220 (correspondingly, the base 220 is provided with a threaded hole, which can be locked with each other with screws), so as to fix the position of the fastener 2252, and thus the handle device 100 fix.
  • the number, shape, and structure of the fastening portions 225 are not limited to this embodiment. It only needs to be combined with the convex portion 221 to fix the handle device 100.
  • the pin 2251 is inserted to a certain depth, it will interfere with The side wall of the handle device 100 is then tightened with screws on both sides of the fastener 2252, so that the position of the pin 2251 is fixed, so that the pin 2251 and the convex portion 221 surround the side wall of the handle device 100.
  • the slider 210 is provided at an end of the base 220, above the side of the clamping portion 150, and a protrusion 211 is provided on the slider 210 for Abutting the bare chip 300
  • the protrusion 211 in this embodiment is a cylinder and is provided with two symmetrically distributed on both sides of the horizontal center axis of the slider 210 (the plane of the bare chip 300 is regarded as a horizontal plane), and
  • a convex portion 221 is located on the extension line of the horizontal central axis of the slider 210, and is provided outside the limiting portion 140.
  • the protrusion 211 (positioning portion 141), the convex portion 221 are formed, etc.
  • FIG. 4 can slide along the horizontal central axis.
  • FIGS. 4 and 5 also show two parts of the slider 210 in the moving direction.
  • Limit blocks (222, 223) are provided on the side for restraining the displacement of the slider 210.
  • the limit blocks (222, 223) are divided into an internal limit block 222 and an external limit block 223, and the internal limit block 222 is close to the bare chip 300 and is provided with one, corresponding to the
  • the outer limit block 223 is provided on a side of the slider 210 facing outward and perpendicular to the surface of the bare chip 300.
  • outer limit blocks 223, which are respectively located at the ends of the slider 210, and the inner limit block 222
  • the outer limit block 223 is fixed on the base 220.
  • a slide groove is provided on the base 220 for installing slide rails 224 that cooperate with the slider 210.
  • slide rail 224 is also provided. 2;
  • the base 220 is provided with an opening in a region corresponding to an end portion of the clamping portion 150, and the slider 210 is located above the clamping portion 150, corresponding to An opening is also provided in the region, and the clamping portion 150 is not in contact with the slider 210, and only the protrusion 211 contacts the bare chip 300. It can be understood that the shape and number of the slider 210 and the protrusion 211 are not limited to this embodiment.
  • the assembly sequence of the positioning device 200, the handle device 100, and the bare chip 300 is the assembly sequence of the positioning device 200, the handle device 100, and the bare chip 300:
  • the base 220 is placed on a platform, the sealing groove 120 is dispensed to be solidified, and then the handle device 100 is placed on the base 220 against the convex portion 221 in a correct manner;
  • the pins 2251 of the adjusting portion 225 and the convex portion 221 are jointly enclosed by the outside of the handle device 100 and fixed;
  • the gap on the bare chip 300 corresponds to the positioning portion 141;
  • the channel 160 of the clamping part 150 is connected to an air pump, and the air pump is turned on.
  • the bare chip 300 is correctly and negatively attached to the handle device 100, and the positioning device 200 is removed.
  • the glue can also be adhered to the back of the bare chip 300, so that the air pump and the positioning device 200 can be removed at the same time after the glue is solidified.
  • the surface of the untouched bare chip 300 can make full use of its area to load gene molecules, and the reaction flux can be greatly improved.
  • the loading process of gene molecules will be described below with reference to FIGS. 6 and 7.
  • the loading of gene molecules on the bare chip 300 requires a certain period of time and harsh reaction conditions, including that the bare chip 300 must not be in contact with air during the reaction, that is to say, the reaction surface of the bare chip 300 needs to be sealed.
  • FIG. 6 shows that the loading device 400 is provided with a cover plate 410 and a bottom plate 420.
  • a groove is formed on the bottom plate 420 to match the handle device 100, and can be directly embedded.
  • the depth of the insertion is the thickness of the handle device 100 (here is the support Distance between the top surface and the bottom surface of the portion 150 or the limiting portion 140); as shown in FIG.
  • the bottom surface of the cover plate 410 is provided with a fan-shaped second sealing groove 411, the arc edge of the second sealing groove 411 and On the inside of the right-angle side (two vertical radii), there are flow channel grooves 412, the midpoint of the arc-side flow channel groove 412, and the right-angle side flow channel groove 412 are provided with liquid outlets (463, 462, 464) near the arc edge.
  • the right-angle side flow channel groove 412 is provided with a liquid inlet 461 near the center of the circle, and the outline of the second sealing groove 411 is closed by glue, and is adhered to the bare chip 300 to form a fan-shaped cavity.
  • second sealing grooves 411 are provided, each of which is a quarter circle, which is enclosed to form a complete circle.
  • the corresponding glue is a circle with an internal cross, which is attached to the bare chip 300 to form 4 Independent fan-shaped cavities.
  • Loading process first locate the assembled bare chip 300 and the handle device 100, and then insert the handle device 100 into the base plate 420 correctly, cover the cover plate 410 (the second sealing groove 411 has been glued and solidified), and lock the cover plate 410 and the bottom plate 420 form a cavity; connect the inlet and outlet (461, 462, 463, 464) and the liquid pump, drain the pipe gas, open the inlet 461 and the corresponding outlet (462, 464) correspondingly
  • the liquid pump fills the flow channel groove 412 with liquid reagents; close the previous liquid outlets (462, 464), and simultaneously open the liquid pump corresponding to the liquid outlet 463, and the liquid flows to the midpoint of the arc; when it reaches the liquid outlet At port 463, the liquid fills the entire cavity.
  • the fluid change process is similar to the above steps.
  • the liquid outlet 462 is first opened to generate a negative pressure to suck the liquid reagent, so that the liquid reagent fills the corresponding right-angle side flow channel groove; and then the liquid outlet 462 is closed to open the liquid outlet.
  • 464 generates a negative pressure to suck the liquid reagent, so that the liquid reagent fills the corresponding right-angle side flow channel groove; finally, the liquid outlet 464 is closed, and the liquid outlet 463 is opened to generate a negative pressure to suck the liquid reagent, so that the liquid reagent fills the corresponding arc-side flow channel groove. , So the liquid fills the entire cavity.
  • the shape and structure of the loading device 400 are not limited to this embodiment, as long as the bare chip 300 does not come into contact with air during the reagent loading process on the reaction surface of the bare chip 300 and is easy to handle after completion (such as setting nesting with the handle device 100) Structure).
  • the number, shape, connection relationship, and the like of each group of the corresponding loading device 400 are also determined according to the actual situation, and are not repeated here.
  • the bare chip 300 completed the loading of the gene molecules.
  • the base molecules in the bare chip 300 need to be subjected to a base pairing reaction one by one in order to obtain the information of each synthetic base indirectly to obtain the gene.
  • the gene sequencer 500 has designed and developed a liquid exchange system with an open reagent tank 520 that automatically completes the liquid addition and exchange operations to control the reaction of the bare chip 300. It is completely immersed (immersed) in the reagent tank 520 and is automatically transported between different reagent tanks 520 of a series of reactions, and the reaction time is automatically controlled.
  • the liquid exchange system includes a plurality of reagent tanks 520, which are used to load various reagents that react with gene molecules; an opening is provided on the top of each reagent tank 520 for the entry of the bare chip 300, At the same time, the leakage of reagents and the fluctuation of the reagent liquid level (mainly a drop phenomenon will cause the bare chip 300 to be completely immersed and the reaction will be insufficient); a side wall of each reagent tank 520 is provided with a positioning tank 170
  • the protruding portion 521 is used for accurately inserting and moving the handle device 100 up and down.
  • the two sides are thin walls (also referred to as “wings” or “wings” or “flange”), and the corresponding reagent grooves 520 A groove is formed on the inner wall of the groove.
  • the cross-section of the groove is “convex” when viewed from the inner surface to the outer surface.
  • the inner wall forms a two-arm embracing shape.
  • the protruding portion 521 it is referred to as the protruding portion 521.
  • the clamping portion 150 is assembled with the robot 510 (the robot 510 is surrounded by The clamping part 150 is around and clamped and fixed), the thickness of the assembly part is greater than the thickness of the handle device 100, and the equipment part is adjustable, on the one hand, it limits the depth of the bare chip 300 to be submerged in the reagent; on the other hand, it can greatly improve the test efficiency in combination with automated control
  • the reaction surface and edge of the bare chip 300 do not touch the reagent tank 520, which can maximize the utilization of the reaction area of the bare chip 300 and improve the utilization rate.
  • the positioning groove 170 and the protruding portion 521 only need to satisfy the positioning and sliding relationship, and are not limited to this embodiment.
  • the back of the handle device 100 may be provided with an extended structure, and the inner side of the positioning groove 170 is provided with a sliding groove. Coordination can also achieve this function, which needs to be considered comprehensively according to actual needs and manufacturing costs.
  • the liquid exchange system also includes a water bath (heating component), a liquid adding component, a draining component, a refrigerator and other parts.
  • the water bath is used to heat the reagent tank 520 to ensure the temperature required for the biochemical reaction.
  • the reagent tank is set at the top.
  • the opening also avoids changing the liquid with water, which affects the reaction; the liquid adding component and the liquid discharging component complete the loading and control of the reagent through the control system; the refrigerator is used to ensure the activity of the reagent.
  • the above-mentioned immersed gene sequencer 500 can directly perform gene molecule loading reaction and sequencing reaction on the bare chip 300 by means of the handle device 100, greatly improving the utilization rate of the sequencing area, saving the consumption of auxiliary materials and saving costs; and using positioning
  • the device 200 can uniformly install the bare chip 300 to the same correct position, with high assembly accuracy and efficiency; the combined robot 510 can automate the program to control the transportation and the reaction process, which improves the sequencing efficiency and has a high degree of automation.

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Abstract

L'invention concerne un dispositif de poignée (100) pour aider une puce nue à effectuer une réaction biochimique, une fente de puce (110) étant disposée au niveau d'une section centrale du dispositif pour le montage d'une puce nue (300), une fente scellée (120) étant disposée dans la fente de puce (110) pour une connexion fixe de la puce nue (300), une fente à vide (130) étant disposée sur un côté interne de la fente scellée (120), la fente à vide (130) étant en communication avec l'extérieur pour aspirer la puce nue (300) sous pression négative, et une fente de positionnement étant disposée sur un côté de la fente de puce (110) pour le positionnement lors de l'administration. Le dispositif de poignée (100) et la puce nue (300) peuvent être appliqués, sous la forme d'un ensemble, à un système de séquençage de gène, obtenant un flux de réaction important, un taux de réutilisation élevé, une utilisation améliorée d'une zone de séquençage, une réduction du matériau et des coûts de fabrication, un fonctionnement pratique, un degré élevé d'automatisation et une bonne efficacité de test.
PCT/CN2018/100817 2018-08-16 2018-08-16 Dispositif de poignée, dispositif de positionnement, dispositif de chargement et séquenceur de gènes WO2020034143A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/CN2018/100817 WO2020034143A1 (fr) 2018-08-16 2018-08-16 Dispositif de poignée, dispositif de positionnement, dispositif de chargement et séquenceur de gènes
CN201880005914.3A CN112955536B (zh) 2018-08-16 2018-08-16 手柄装置、定位装置、加载装置及基因测序仪

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2018/100817 WO2020034143A1 (fr) 2018-08-16 2018-08-16 Dispositif de poignée, dispositif de positionnement, dispositif de chargement et séquenceur de gènes

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WO2020034143A1 true WO2020034143A1 (fr) 2020-02-20

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Cited By (7)

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