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CN117126729A - Efficient moving integrated machine for sample detection and control method thereof - Google Patents

Efficient moving integrated machine for sample detection and control method thereof Download PDF

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Publication number
CN117126729A
CN117126729A CN202311063582.3A CN202311063582A CN117126729A CN 117126729 A CN117126729 A CN 117126729A CN 202311063582 A CN202311063582 A CN 202311063582A CN 117126729 A CN117126729 A CN 117126729A
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consumable
driving unit
module
time period
move
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Inventor
孙瑶
袁双华
田真
龚大江
李政
苗保刚
李明
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Xi'an Tianlong Science & Technology Co ltd
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Xi'an Tianlong Science & Technology Co ltd
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Priority to CN202311063582.3A priority Critical patent/CN117126729A/en
Publication of CN117126729A publication Critical patent/CN117126729A/en
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING 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
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6806—Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING 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
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844—Nucleic acid amplification reactions
    • C12Q1/686—Polymerase chain reaction [PCR]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING 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
    • C12Q3/00—Condition responsive control processes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584—Control arrangements for automatic analysers

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  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Physics & Mathematics (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • General Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Pathology (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

The invention discloses a high-efficiency moving sample detection all-in-one machine and a control method thereof, and relates to the field of medical equipment; the high-precision low-speed drive and the low-precision high-speed drive are matched with each other, so that the moving process can have high speed and high precision.

Description

Efficient moving integrated machine for sample detection and control method thereof
Technical Field
The invention relates to the field of medical instruments, in particular to an integrated machine for detecting a sample in an efficient moving mode and a control method thereof.
Background
In vitro diagnostic techniques have been developed to provide an important means for in vitro analysis of various samples such as blood, feces, swab-type collection solutions, etc., related to organisms, and nucleic acids are required to be isolated, purified and amplified for detection as carriers of genetic information of organisms, both for research of nucleic acid sequences and structures and for exploration of gene functions and expression, and therefore, are very necessary for purification and quantitative or qualitative analysis of nucleic acids.
In the prior art, for nucleic acid detection, a relatively large number of processing steps are needed in the middle, and reagent reaction liquid requirements and environments needed in the processing steps are often different, so that different reactions are optimally selected to be carried out on different consumable hole sites, and a pipetting module, an extraction module and the like are required to be moved to carry out corresponding operations among different hole sites, so that the operations of automatic transfer, extraction and purification of nucleic acid, establishment of an amplification system and the like are completed.
For example, nucleic acid extraction or other related nucleic acid reactions involving sample transfer, lysis, washing, and elution require a pipetting module to transfer sample fluid from a sample tube to an extraction consumable, the applied extraction consumable being configured with pipetting consumable holes, reserved holes, lysis holes, magnetic bead retention holes, washing holes, elution holes, magnetic rod sheath holes, and eluent holes, the extraction module moving between different holes of the extraction consumable to perform purification elution of the sample. And transferring the eluent to the amplification consumable by a pipetting module, wherein the applied amplification consumable is provided with a premixing hole site, a sealing liquid hole site and a plurality of amplification hole sites, the pipetting module moves among different hole sites of the amplification consumable to execute the establishment of an amplification system, the idealized execution of all the processes is the full-automatic integrated analysis of sample inlet and outlet, and the design of the integrated consumable and corresponding integrated equipment becomes the design target of more and more manufacturers under the driving of the requirement.
Chinese invention patent CN107727874B and CN106996984B protect a pure integrated consumable design, integrate the pipetting consumable, the extracting consumable and the PCR amplification consumable in the extracting process, design the consumable which can be adapted to different requirements of sample extraction and amplification, the number of the amplification holes of the design is less, it is difficult to execute more target detection, and the sealing of the consumable is difficult after use, and there is pollution risk; chinese invention patent CN106148512B, name: the method for scanning the real-time micro-fluid thermal cycler and the method for synchronous thermal cycle and scanning optical detection provides a scheme for performing extraction and amplification detection by using micro-fluid consumables, and the design can be operated in a closed state to reduce the pollution risk of a system, but the consumable processing is complex, and micro-channels with small sizes, particularly with the size below 0.5mm, are required to be designed under the small size due to more influencing factors such as capillary force, surface tension and the like, so that the design complexity of the channels is greatly increased, and under special conditions, a micro-fluid valve is required to be configured to restrict the fluid movement range; chinese invention patent application CN114364811a, title: the design requires reliable sealing between the amplification hole site and the extraction elution hole site after the transfer of the eluent is completed, otherwise, the execution of thermal cycle type amplification can lead to the cross contamination of liquid reflux under the drive of temperature, but for the constant temperature amplification type scheme, the design can ensure that the cross contamination risk such as reflux and the like does not exist between the amplification chamber and the extraction elution hole by means of bending the capillary length; the scheme of the U.S. patent 9857384B2 is that the kit is designed into a separable type, the kit can be processed and produced according to different production processes in the processing and production stage, and different kits can be spliced and combined to be matched with an integrated instrument for use in the actual use stage. From the prior art to analyze, the integrated detection device is increasingly required to perform more multi-target analysis, and the analysis target of sample input and output can be realized at lower cost by adopting a segmented large-size consumable design, while the integrated instrument of multiple detection and larger flux means that the travel range is too long, and in this case, the sample processing speed and the operation precision of different processing steps are also required to be considered.
When the existing integrated machine sample detection device moves, the single driving source is used for driving the movement of the pipetting module, the extraction module and the like, and the single driving source only has one movement speed and one movement precision, if the movement with high precision is required, the movement speed is reduced, the detection efficiency is low, the waiting time in the detection process is long, and the detection accuracy is not good; otherwise, if the moving speed is increased, the moving precision is reduced, the problems of misalignment of hole sites and the like are easy to occur, and the detection result is affected.
Disclosure of Invention
The invention aims at: in view of the above problems, the present invention provides an integrated machine for detecting a sample with high efficiency and a control method thereof, wherein the integrated machine is divided into an upper area driven by an upper driving unit and a lower area driven by a lower driving unit, and the upper driving unit and the lower driving unit are matched to move, so that the moving process can have high speed and high precision, the detection efficiency and the detection accuracy are improved, and the integrated machine can adapt to high-throughput multiple detection application scenarios.
The technical scheme adopted by the invention is as follows:
an efficient mobile sample testing all-in-one machine, comprising an upper region and a lower region; the upper region comprises an upper driving unit and a combined module, the upper driving unit can drive the combined module to horizontally move, and the combined module comprises a pipetting module and an extraction module; the lower region comprises a lower driving unit and a bearing table, the bearing table comprises a sample tube region, an extraction consumable region and an amplification consumable region, and the lower driving unit can drive the bearing table to move horizontally; the time period that upper portion drive unit drive combination module moved is the first time period, the time period that lower part drive unit drive plummer moved is the second time period, there is overlap time period between first time period and the second time period, upper portion drive unit and lower part drive unit mutually support for the pipetting module can move and carry out sample liquid transfer operation, the pipetting module can move and carry out sample extraction purification operation in the pipetting consumable, the pipetting module can move and carry out eluent transfer operation, pipetting module can move and carry out solution distribution operation in the amplification consumable in the region of the pipetting consumable between the region of the pipetting consumable and the amplification consumable.
Further, the upper driving unit drives the combination module with a first precision, the combination module moves horizontally at a first speed under the action of the upper driving unit, the lower driving unit drives the carrying platform to move horizontally at a second speed under the action of the lower driving unit, and the first precision is higher than the second precision and the first speed is lower than the second speed, or the first precision is lower than the second precision and the first speed is higher than the second speed.
Further, the lower driving unit comprises a first motor and a second motor, the first motor can drive the bearing table to move within a first movement distance, the second motor can drive the bearing table to move within a second movement distance, and the first motor and the second motor are mutually matched to enable the movement distance of the bearing table not to exceed the sum of the first movement distance and the second movement distance; the first motor and the second motor can be matched with each other to drive the bearing table to carry out loading configuration operation outside the shell; the first motor and the second motor work in series.
Further, the combination module further comprises an identification module, and the upper driving unit can be matched with the lower driving unit, so that a first time period for moving the corresponding identification module and a second time period for moving the corresponding bearing platform at least partially overlap; the consumable identification camera of the identification module can execute dynamic code scanning identification or static code scanning identification.
Further, the liquid transferring module can transfer liquid and uniformly mix liquid at a first liquid discharging speed and a second liquid discharging speed, and the first liquid discharging speed is 1/4-1/2 of the second liquid discharging speed.
The control method of the high-efficiency movable sample detection integrated machine comprises the following steps of,
sample liquid transferring step: the upper driving unit drives the pipetting module to move in a first time period, the lower driving unit drives the bearing table to move in a second time period, the first time period and the second time period are at least partially overlapped, and the upper driving unit and the lower driving unit are matched with each other to drive the pipetting module to move between the sample tube and the cracking hole site of the extraction consumable to execute sample liquid transferring operation;
sample extraction and purification steps: the upper driving unit drives the extraction module to move in a first time period, the lower driving unit drives the bearing table to move in a second time period, the first time period and the second time period are at least partially overlapped, and the upper driving unit and the lower driving unit are mutually matched to drive the extraction module to move between all hole sites of the extraction consumable to perform sample extraction and purification operation;
And (3) an amplification system establishment step: the upper driving unit drives the pipetting module to move in a first time period, the lower driving unit drives the bearing table to move in a second time period, the first time period and the second time period are at least partially overlapped, the upper driving unit and the lower driving unit mutually cooperate to drive the pipetting module to move between an elution hole site for extracting consumable materials and a premixing hole site for amplifying the consumable materials to perform eluent transfer operation, the pipetting module performs n times of mixing operation on the premixing hole site, n is a positive integer, the mixing operation is that the pipetting module absorbs eluent in the elution hole site, then the eluent is discharged into the premixing hole site, and after the eluent is mixed with freeze-drying reagent, the upper driving unit and the lower driving unit mutually cooperate to drive the pipetting module to move between each hole site for amplifying the consumable materials to perform solution distribution operation.
Further, in the step of establishing the amplification system, the pipetting module transfers the eluent from the eluting hole sites of the extracting consumable to the premixing hole sites of the amplifying consumable m times, wherein m is an integer greater than or equal to 2.
Further, in the amplification system establishment step, the pipetting module transfers and discharges liquid at a first liquid discharge speed in the pipetting process, and mixes and discharges liquid at a second liquid discharge speed in the mixing operation, wherein the first liquid discharge speed is 1/4-1/2 of the second liquid discharge speed.
Further, the method also comprises the following steps before the sample liquid transferring step
Loading configuration: the first motor and the second motor in the lower driving unit work in series to drive the bearing table to be outside the shell, the sample tube is loaded in the sample tube region, the extracting consumable is loaded in the extracting consumable region, the amplifying consumable is loaded in the amplifying consumable region, and after loading is completed, the first motor and the second motor work in series to drive the bearing table to return to the shell.
Further, after the loading configuration step, the method also comprises
Scanning code identification: the upper driving unit drives the identification module to move in a first time period, the lower driving unit drives the bearing table to move in a second time period, the first time period and the second time period are at least partially overlapped, the identification module respectively scans and identifies the extracted consumable and the amplified consumable, wherein when the upper driving unit and the lower driving unit are simultaneously driven, the consumable identification camera of the identification module performs dynamic code scanning, and when the upper driving unit is independently driven, the consumable identification camera of the identification module performs static code scanning.
In summary, due to the adoption of the technical scheme, the beneficial effects of the invention are as follows:
1. according to the invention, the upper driving unit and the lower driving unit are matched to move, so that the waiting time in the detection process is reduced, and the detection efficiency and the detection accuracy are improved.
2. The invention adopts the mutual cooperation of high-precision low-speed driving and low-precision high-speed driving, so that the moving process can have high speed and high precision.
3. The lower driving unit is a double-motor mechanism, so that longer and more stable movement can be realized in a limited space, and the miniaturization of the integrated machine mechanism is realized.
4. The first motor and the second motor of the lower driving unit work in series, so that adverse factors such as resonance or noise superposition are avoided when the two motors are driven by the same bearing table at the same time.
5. The invention can efficiently and quickly execute code scanning identification.
6. When the eluent is transferred, the eluent is added in a divided manner, so that the problem that the eluent overflows due to the fact that the freeze-drying reagent cannot be dissolved immediately due to excessive amount of the eluent added at one time is avoided.
7. The pipetting module adopts low liquid discharge speed in pipetting process, can ensure that no bubbles are generated in pipetting and liquid separation, adopts high liquid discharge speed in mixing operation, and ensures that eluent and freeze-drying reagent are mixed uniformly and efficiently and the mixing process is more sufficient.
Drawings
FIG. 1 is a schematic diagram of a functional module of an all-in-one machine of the present invention;
FIG. 2 is a schematic view of the internal structure of the integrated machine of the present invention;
FIG. 3 is a schematic view showing an internal structure of the integrated machine in another state of the invention;
FIG. 4 is a schematic view of the structure of the lower driving unit of the present invention;
FIG. 5 is a schematic view of the structure of the bearing table and the lower driving unit of the present invention;
fig. 6 is a schematic diagram of the driving principle of the lower driving unit of the present invention;
FIG. 7 is a schematic view of the overall appearance of the integrated machine of the present invention;
FIG. 8 is a schematic diagram of the sample fluid transfer principle of the present invention;
FIG. 9 is a schematic diagram of the principle of the nucleic acid extraction purification operation performed by the extraction consumable of the present invention;
FIG. 10 is a schematic diagram of the eluent transfer principle of the present invention;
FIG. 11 is a schematic diagram of the amplification consumables of the present invention performing an amplification system setup operation;
FIG. 12 is a schematic view of the structure of the sample tube switch cover mechanism of the present invention;
FIG. 13 is a schematic view of the structure of a pipetting module of the invention;
FIG. 14 is a schematic diagram of the structure of the extraction module of the present invention;
FIG. 15 is a schematic view of a second air chute and a fourth air chute of the present invention;
FIG. 16 is a control timing diagram of the all-in-one machine of the present invention;
FIG. 17 is a block diagram of a control module of the all-in-one machine of the present invention.
The marks in the figure: 20-sample tube switch cover mechanism, 30-extraction consumable switch cover mechanism, 40-identification module, 50-pipetting module, 60-extraction module, 70-amplification consumable switch cover mechanism, 101-first motor, 102-first lead screw, 103-first slider, 104-first platform, 105-first rail, 106-chute assembly, 201-second motor, 202-second lead screw, 203-second slider, 204-carrier, 205-slide chamber, 207-second rail, 208-chute unit, 301-housing, 302-opening and closing part, 303-automated loading zone, 304-sample zone, 305-extraction consumable zone, 306-amplification consumable zone, 307-cooling fin, 308-bottom fan, 309-exhaust channel, 310-optical detection module, 315-third motor, 316-third lead screw, 801-first vent, 802-second vent, 8021-independent air channel, 8022-top fan, 803-third vent, 8031-middle fan, 804-fourth vent.
Detailed Description
The present invention will be described in detail with reference to the accompanying drawings.
The present invention will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
Example 1
An efficient mobile sample testing all-in-one machine, as shown in FIGS. 1-15, includes an upper region and a lower region; the upper region comprises an upper driving unit and a combined module, the upper driving unit can drive the combined module to horizontally move, and the combined module comprises a pipetting module 50 and an extraction module 60; the lower region comprises a lower driving unit and a carrying platform 204, the carrying platform 204 comprises a sample tube region 304, an extraction consumable region 305 and an amplification consumable region 306, and the lower driving unit can drive the carrying platform 204 to move horizontally; the period of time that the upper driving unit drives the combined module to move is a first period of time, the period of time that the lower driving unit drives the carrying table 204 to move is a second period of time, an overlapping period of time exists between the first period of time and the second period of time, and the upper driving unit and the lower driving unit are matched with each other, so that the pipetting module 50 can move between the sample tube region 304 and the pipetting consumable region 305 to perform a sample liquid transferring operation, the pipetting module 60 can move between the pipetting consumables to perform a sample extraction and purification operation, the pipetting module 50 can move between the pipetting consumable region 305 and the amplifying consumable region 306 to perform an eluent transferring operation, and the pipetting module 50 can move between the amplifying consumable region 306 to perform a solution dispensing operation.
The pipetting module 50 can transfer the sample or the solution containing the nucleic acid fragments, the pipetting module 50 comprises a pipetting device, a pipetting device driving motor for driving the pipetting device to move up and down for position adjustment and a working motor for driving the pipetting push rod, the pipetting device can change the internal pressure of consumable materials by regulating the relative position of the pipetting push rod and a matching chamber, so that pipetting and draining operations are performed, the pipetting device can share the sample or the nucleic acid fragment solution, and different pipetting Tip heads and pipetting heads can be used in different stages; in other embodiments, separate pipettes may also be used to pipette the sample or the solution containing the nucleic acid fragments, respectively. The operation of parallel processing of more sample fluid aspirates can be achieved by a design of, for example, 8 pipetting heads, the specific number being not limited here with reference to fig. 13.
The extracting module 60 can stir and adsorb the nucleic acid fragments to the solution containing the nucleic acid fragments and transfer the nucleic acid fragments, which can be specifically a magnetic stirring installation part and a magnetic rod sleeve, the magnetic stirring installation part and the magnetic rod sleeve can be used for realizing the effect of extracting and stirring the nucleic acid, and the stirring can use an up-down oscillation or rotation stirring mode, as shown in fig. 14, a compound type motion scheme of driving 8 magnetic stirring installation parts by an independent driving motor and driving by a down oscillation motor is adopted.
The upper driving unit drives the combination module with a first precision, the combination module moves horizontally at a first speed under the action of the upper driving unit, the lower driving unit drives the carrying platform 204 to move horizontally at a second speed under the action of the lower driving unit, and the first precision is higher than the second precision and the first speed is lower than the second speed.
The lower driving unit comprises a first motor 101 and a second motor 201, the first motor 101 can drive the bearing table 204 to move within a first movement distance, the second motor 201 can drive the bearing table 204 to move within a second movement distance, and the first motor 101 and the second motor 201 are mutually matched so that the movement distance of the bearing table 204 does not exceed the sum of the first movement distance and the second movement distance; the casing 301 is provided with an opening and closing part 302, and in the opened state of the opening and closing part 302, the first motor 101 and the second motor 201 can cooperate with each other to drive the loading platform 204 outside the casing 301, so that the automatic loading area 303 in the loading platform 204 is fully exposed outside the range contained in the casing 301 for loading configuration operation. The automatic loading area 303 comprises a sample area 304, an extraction consumable area 305 and an amplification consumable area 306, wherein the sample area 304, the extraction consumable area 305 and the amplification consumable area 306 are arranged in a straight shape parallel to the direction of the in-out opening and closing part 302, so that detection of more targets can be realized in a limited space, and high integration of the instrument is ensured. The automated loading area 303 may comprise several loading units, here illustrated as 8, arranged in parallel, each comprising a sample tube, an extraction consumable and an amplification consumable, by means of which multi-target multiplex detection of not more than 8 samples can be achieved. Sample pipe is placed in sample district 304 under the closed state, draws the consumptive material and is placed in drawing the consumptive material district 305 under the closed state, and the amplification consumptive material is placed in the amplification consumptive material district 306 under the closed state, guarantees like this that loading process can not produce the pollution risk to the operator, and the operation security is higher.
In this embodiment, the principle of the first motor and the second motor is as disclosed in application number 202211094300.1, and the dual-motor driving structure and the nucleic acid extraction detection integrated machine driven by the same, where the bearing table 204 is connected with the first slider 103, so that when the first slider 103 moves along the length direction of the first screw rod 102, the first slider 103 can drive the bearing table 204 to move along the length direction of the first screw rod 102, the first slider 103 can be sleeved on the first screw rod 102, the first screw rod 102 is fixed on the first platform 104 through the bearing seat, the first motor 101 is connected with the first screw rod 102 through the coupler and/or the encoder, the first motor 101 rotates to drive the first screw rod 102 to synchronously rotate between the two bearing seats, so as to accurately move the first slider 103 on the first screw rod 102.
The first platform 104 may be provided with a first guide rail 105, the chute assembly 106 connects the bearing platform 204 with the first guide rail 105 in a matching manner, the chute assembly 106 connects the bearing platform 204 with the first slider 103 directly or indirectly, for example, the chute assembly may be fixedly connected by a sheet-shaped connecting piece, so as to drive the bearing platform 204 to freely move along the length direction of the first guide rail 105.
The second slider 203 can move along the length direction of the second screw 202, so that the limit absolute movement distance of the second slider 203 is more than the distance that the first slider 103 can move on the first screw 102 or the distance that the second slider 203 can move on the second screw 202, and the sum of the two distances is not more than.
The second motor 201 can be arranged at the bottom of the bearing table 204, a bearing seat for fixing the second screw rod 202 is arranged at the bottom of the bearing table 204, the second motor 201 is driven with the second screw rod 202 through a belt wheel, or the second motor 201 is driven with the second screw rod 202 through a gear, so that the second motor 201 drives the second screw rod 202 to rotate at the bottom of the bearing table 204, and the second sliding block 203 sleeved on the second screw rod 202 can accurately move.
The bearing table 204 may be provided with a sliding cavity 205 for the second slider 203 to move, and the second slider 203 is limited in the sliding cavity 205 to be fixed; a second guide rail 207 is arranged at the bottom of the bearing table 204, a sliding groove unit 208 matched with the second guide rail 207 is arranged on the sliding groove assembly 106, the sliding groove unit 208 is matched with the second guide rail 207, a guiding effect is provided for the movement of the bearing table 204, so that the second sliding block 203 moves along the length direction of the second screw rod 202, the second guide rail 207 of the bearing table 204 and the sliding groove unit 208 move relatively in the length direction of the second guide rail 207, and the bearing table 204 can stably move under the drive of the second motor 201 through two second guide rails 207 and two sliding groove units 208 which are oppositely arranged.
The control method of the first motor 101 and the second motor 201 may be that the first motor 101 is started first, and then the second motor 201 is started, that is, the first slider 103 drives the carrying platform 204 to move to a first limit distance, and then the second slider 203 drives the carrying platform 204 to move to a preset limit distance, so as to control, where the first motor 101 and the second motor 201 work in series, so as to avoid adverse factors such as resonance or noise superposition when the two motors drive the same carrying platform at the same time.
The chute assembly 106 realizes the serial linkage of the relative movement driven by different driving units with the same reference, so that the design reliability is higher, and specifically, when the first motor 101 drives the first sliding block 103 to move through the first screw rod 102, the chute assembly 106 drives the whole bearing table 204 to move along the length direction of the first guide rail 105 under the guidance of the first guide rail 105, when the second motor 201 drives the second sliding block 203 to move through the second screw rod 202, the movement state of the chute unit 208 is the same as that of the chute assembly 106, and at the moment, if the first motor 101 does not work, the chute unit 208 is still, and the second sliding block 203 drives the second guide rail 207 of the bearing table to move, so that the two different driving mechanisms are driven by the same chute assembly 106 to achieve the serial relay movement with the double motor reliability.
The first motor 101 on the first platform 104 drives the first slider 103 through the first screw rod 102 to realize free movement within the length range of D10, in practical implementation, because the requirement of positioning and the like is required, the practical movement range is shorter than the practical movement range of the first slider 103 which can be supported by the first screw rod 102, the whole length of the whole first screw rod 102 with the thread section is theoretically, a practical position sensor such as a photoelectric switch and the like can be arranged at a preset position, and the second motor 201 carried by the bearing platform 204 can realize free movement within the length range of D20 through driving the second slider 203, so that the practical movement range of the second screw rod 202 is relatively shorter. Finally, the absolute limit movement distance that can be achieved by the second slider 203 is D30 by using the dual-motor driving mechanism combined by the same chute assembly 106, and the length of the absolute limit movement distance exceeds the movement distance that can be achieved by the first slider 103 on the first screw rod 102 or the movement distance that can be achieved by the second slider 203 on the second screw rod 202, and the sum of the two distances is not exceeded, so that the dual-motor can achieve a larger movement distance range on the premise of stability and reliability.
The upper driving unit includes a third motor 315 and a third screw 316.
The third screw 316 has a pitch smaller than the pitch of the first screw 102 and/or the second screw 202 to ensure accuracy of operation.
The integrated machine further includes an extraction consumable switch cover mechanism 30 for opening and closing the extraction consumable, an amplification consumable switch cover mechanism 70 for opening and closing the amplification consumable, and a sample tube switch cover mechanism 20 for opening and closing the sample tube.
The consumable extraction and consumable extraction cover opening and closing mechanism 30 may adopt a prior art structural design, such as a nucleic acid reaction consumable cover opening and closing mechanism disclosed in application number CN111847343a, and the consumable extraction cover opening and closing mechanism 30 includes a first architecture layer, a second architecture layer and a third architecture layer; a plurality of first guide rods are vertically arranged below the first architecture layer, the upper ends of the first guide rods are connected with the first architecture layer, and the lower ends of the first guide rods penetrate through the second architecture layer and the third architecture layer; a plurality of second guide rods are vertically arranged between the second framework layer and the third framework layer; the upper end of the second guide rod penetrates through the second framework layer, and the lower end of the second guide rod is connected with the third framework layer; an elastic component is sleeved on the second guide rod; the first architecture layer is connected with the second architecture layer through a lifting device, and the lifting device is used for driving the second architecture layer to move up and down along the first guide rod; the consumable cover fixing mechanism is arranged on the second framework layer and used for fixing the consumable cover on the second framework layer; be provided with consumptive material main part fixed establishment on the third framework layer, consumptive material main part fixed establishment is used for restricting the consumptive material main part and removes.
The consumable extracting device comprises a consumable main body and a consumable cover; the consumable main body comprises a connecting plate and a plurality of pipe bodies inserted into the connecting plate, the pipe bodies are provided with pipe openings, the pipe openings of all the pipe bodies are in the same plane, and the width of the connecting plate is larger than the diameter of the pipe openings so as to form a first cornice used for fixing the pipe bodies when the cover is opened on the outer side walls of the pipe bodies; the consumable cover comprises a plurality of pipe covers which are in one-to-one correspondence with the pipe bodies and are used for blocking the pipe orifices, the pipe covers are connected to the same side of the pipe cover plate, and the edges of the pipe covers are provided with second cornices which serve as stress points when the pipe covers are pulled up from the pipe bodies; when the pipe cover is covered on the pipe body, a gap is formed between the second cornice and the first cornice, so that the consumable switching cover mechanism 30 is convenient to extract and insert from the gap, and the cover opening operation is further realized.
The extraction consumable is 10 hole site connecting pipe consumable, and is configured with a first pipetting consumable hole site, a reserved hole site and a cracking hole site from the near to the far according to the relative position with the sample pipe, wherein the magnetic bead is used for storing the hole site, washing the A hole site, washing the B hole site, washing the C hole site, eluting the hole site, a magnetic rod sleeve hole site and a second pipetting consumable hole site. The wash liquid in the wash A well may be 600-700. Mu.L, the wash liquid in the wash B well may be 650-750. Mu.L, the wash liquid in the wash C well may be 750-850. Mu.L, and the wash liquid in the wash well may be 150-250. Mu.L to perform more thorough washing and elution operations. When the detection object is bacteria, the reserved hole contains proteinase K reagent, the liquid transfer module 50 can transfer the sample liquid to the reserved hole to execute the dissolution and the destruction of protein capsid, and then the liquid transfer module 50 can transfer the solution in the reserved hole to the cracking hole, so that the integrated bacterial sample detection liquid can be used for processing virus sample detection, and the compatibility is stronger. The heating units are arranged on the cracking hole site, the magnetic bead preservation hole site and the elution hole site, heating in the cracking hole site can be compensated by the heating temperature of the adjacent magnetic bead preservation hole site, so that the cracking is more sufficient, the yield of the nucleic acid fragments can be improved, the detection accuracy can be ensured, the physical properties of the magnetic beads cannot be influenced by the arrangement of the heating unit liquid in the magnetic bead preservation hole site, the whole reaction cannot be adversely affected, part of the hole sites of the connecting tube extraction consumable can be combined or split in the actual use process, and the connecting tube consumable of the types of 9 hole sites, 8 hole sites, 11 hole sites, 12 hole sites and the like can be formed, and the number of the hole sites is not less than 8 hole sites in order to ensure the extraction effect. In this solution, two ends of the 10-hole site connecting tube consumable are respectively a first pipetting consumable hole site and a second pipetting consumable hole site which are adapted to pipetting consumables with different capacities, and the capacity of the first pipetting consumable (pipetting consumable used for transferring sample liquid) can be configured to be more than twice that of the second pipetting consumable (pipetting consumable used for transferring eluent), so that the sample liquid can be efficiently transferred in sufficient quantity, the eluent and the PCR premix liquid can be accurately and slightly transferred, different transfer requirements are met, as shown in fig. 8, wherein the pipetting consumable close to the sample tube is a sample liquid pipetting consumable with a first capacity and is used for transferring the sample liquid from the sample tube to a lysis hole site for extracting the consumable in cooperation with the pipetting module 50, the lower driving unit can drive the bearing table 204 to horizontally move, the first motor 101 of the lower driving unit can drive the bearing table 204 to horizontally move through the first screw 102, the upper driving unit drives the combined module in a first time period with an overlapping time period between the upper driving unit and a second time period driven by the lower driving unit, so as to drive the pipetting module 50 to rapidly and highly accurately perform the operation of transferring the sample liquid to the cracking hole site, after the operation is completed, the sample liquid pipetting consumable is recovered into the first pipetting consumable hole site, the top fan 8022 can continuously operate in the process, the environment of the pipetting consumable is rapidly switched by matching with the driving of the upper driving unit and the lower driving unit with the overlapping time period, the pollution risk is reduced, the exposure time of the sample liquid pipetting consumable contacted with the sample liquid is shortened, the pollution risk is reduced, one end of the magnetic rod sleeve hole site, which is far away from the sample liquid pipetting consumable, is configured at the other end, which is far away from the first pipetting consumable hole site, of the 10-hole connecting consumable, and next to the second pipetting consumable hole site, an eluent pipetting consumable with a second capacity is configured in the second pipetting consumable hole site, the eluent pipetting consumable is used for transferring eluent to the amplification consumable, fig. 9a illustrates that the extraction module 60 moves to the bar sleeve hole site to connect with the bar sleeve and then moves to the magnetic bead preservation hole site, fig. 9B illustrates that the bar descends and stretches into the bar sleeve, the magnetic beads are adsorbed in the bar sleeve from the magnetic bead preservation hole site, the extraction module 60 transfers the magnetic beads to the cracking hole site, the magnetic beads are adsorbed in the magnetic bead preservation hole site and transferred to the cracking hole site, in the process, the upper driving unit and the lower driving unit can have overlapping time periods to respectively drive the combination module and the bearing table 204, the efficient nucleic acid fragment adsorption with low pollution risk can be realized, fig. 9C illustrates that the bar sleeve is uniformly mixed in the cracking hole site by vibrating and rotating, FIG. 9d illustrates the magnetic bead adsorption cleavage of a nucleic acid fragment, the extraction module transferring 60 to the washing A site, FIG. 9e illustrates the nucleic acid fragment being washed and purified in the washing A site, FIG. 9f illustrates the extraction module 60 being transferred to the washing B site, FIG. 9g illustrates the nucleic acid fragment being washed and purified in the washing B site, FIG. 9h illustrates the extraction module 60 being transferred to the washing C site, FIG. 9i illustrates the nucleic acid fragment being washed and purified in the washing C site, FIG. 9j illustrates the extraction module 60 being transferred to the elution site, FIG. 9j being performed directly to the elution site after the washing purification of FIG. 9g is completed for some viruses without performing FIGS. 9h, FIG. 9i, FIG. 9k illustrating the release of the nucleic acid fragment being completed in the elution site, FIG. 9l illustrates the magnetic bead being transferred to the bead preservation site as recovered at S1, the magnetic bar sleeve being placed back to the magnetic bar sleeve site as per S2, the whole process of sample extraction and purification is carried out by matching the magnetic bead method with the 10-hole site connecting tube consumable, and in the whole operation process, the overlapping displacement does not exist in the extraction and purification process of matching the magnetic rod sleeve and the sample liquid transfer process of matching the sample liquid pipetting consumable, so that the risk of cross contamination to the extraction process due to possible volatilization of samples is reduced.
The principle of the amplification consumable is as disclosed in application No. 202211518935.X, wherein the amplification consumable comprises a pre-mixing part storing freeze-dried non-specific reagents which do not correspond to targets, 6 cup-separating holes physically spaced from the pre-mixing part, the number of the cup-separating holes can be other, the number 6 is a preferred embodiment, at least one cup-separating hole comprises primer probe reagents corresponding to not less than M targets in the 6 cup-separating holes, M is an integer not less than 2, and the primer probe reagents are stored in a second dry state. The liquid sealing reagent storage device also comprises a liquid sealing reagent storage part, wherein paraffin oil is stored in the liquid sealing reagent storage part. Fig. 10 illustrates the eluent transfer operation performed by the second volume of eluent pipetting consumables in conjunction with pipetting module 50, pipetting module 50 connecting the eluent pipetting consumables, then moving to the eluent hole site to aspirate the eluent in accordance with S3, then transferring the eluent into the premix of the amplification consumables in two times in accordance with S4. Similarly, the upper driving unit and the lower driving unit can drive the combination module and the bearing table 204 in an overlapping time period, so that eluent transfer can be performed quickly and with low pollution risk, and the two types of pipetting consumable holes are arranged at the two ends of the 10-hole site connecting consumable separately, so that the risk of cross pollution caused by volatilization of sample liquid is avoided to the greatest extent, and the detection result with small difference can be accurately and repeatedly obtained by the integrated machine. In the transferring process of the eluent, firstly, a first volume of the eluent is transferred, so that part of the lyophilized non-specific reagent is dissolved, the spare volume in the premixing part is increased, then, a second volume of the eluent is transferred, the eluent pipetting consumable performs several times of liquid sucking and draining in the premixing part, the eluent and the non-specific reagent can be fully mixed without pollution, the to-be-dispensed premix is obtained, and different pipetting consumables are not required to be configured due to the need of performing premixing and mixing and cup separation of the premix. As shown in fig. 11a and 11b, the pre-mixed liquid after fully mixing is sequentially transferred into each cup-separating hole site by the eluent pipetting consumable, the pre-mixed liquid is separated by the pipetting module in a multi-suction multi-row mode, so that the pre-mixed liquid in each cup-separating hole site is consistent as much as possible, the accurate liquid separation amount is ensured, after the pre-mixed liquid is distributed, as shown in fig. 11c, the pipetting module sucks paraffin oil smaller than the pre-mixed liquid from the liquid sealing reagent storage part in a multi-suction mode and transfers the paraffin oil into each cup-separating hole site, the volume of the paraffin oil in each cup-separating hole site is optimally between 1/2 and 4/5 of the transferred pre-mixed liquid, so that the amplification reaction speed in the cup-separating hole site is not influenced by the paraffin oil transfer amount, the problem of false negative caused by insufficient amplification is avoided, on the other hand, the evaporation of the pre-mixed liquid with reduced liquid sealing as much as possible can be realized by the sufficient coverage of the paraffin oil on the pre-mixed liquid is ensured, the detection sensitivity and accuracy are not influenced, as shown in fig. 11d, and finally the amplification cover is performed, so that the subsequent operation is performed.
The amplification consumable switch cover mechanism 70 can adopt the prior art structural design, such as a consumable switch cover structure disclosed in application number CN111847344a, and comprises an adapter plate, a consumable cover fixing plate and a consumable main body fixing plate; the adapter plate, the consumable cover fixing plate and the consumable main body fixing plate are sequentially arranged from top to bottom; the adapter plate and the consumable body fixing plate are movably sleeved on a plurality of vertically arranged guide rods and can move up and down along the guide rods, an upper guide rod limiting block is arranged at the upper end of each guide rod, the upper guide rod limiting block is positioned above the adapter plate, a lower guide rod limiting block is arranged at the lower end of each guide rod, and the lower guide rod limiting block is positioned below the consumable body fixing plate; the adapter plate is connected with the consumable cover fixing plate through a plurality of guide rods II; the consumable cover fixing mechanism is arranged at the bottom of the consumable cover fixing plate; a plurality of consumable main body fixing grooves are formed in the consumable main body fixing plate.
Of course, the amplification consumable cover opening and closing mechanism 70 can integrate the function of a hot cover, so that the top temperature is ensured to be higher under the condition that the top of the amplification consumable is abutted in the amplification process, and the problems of condensation and the like caused by cold wall surfaces in the thermal cycle process are reduced or even avoided.
The sample tube includes a container body and a container cap.
The sample tube cover opening and closing mechanism 20 can adopt a prior art structural design, such as a rotary cover opening and closing mechanism disclosed in application number 202211017823.6, and comprises a cover screwing assembly for driving the container cover to rotate relative to the container body and unscrewing or closing the container body; the lifting assembly is connected with the spiral cover assembly and is used for driving the spiral cover assembly to at least complete vertical movement; the cap screwing assembly comprises a rotating head provided with an external thread structure, the external thread structure can be matched and connected with the internal thread of the container cap of the sample tube, and the container cap is driven to rotate anticlockwise or clockwise by rotating anticlockwise or clockwise, so that the container cap is turned on or turned off.
The combination module further comprises an identification module 40, the upper drive unit being cooperable with the lower drive unit such that a first period of time during which the corresponding identification module 40 moves at least partially overlaps a second period of time during which the corresponding carrier 204 moves; the consumable identification camera of the identification module 40 may perform dynamic scan code identification or static scan code identification. The extracting consumable and the amplifying consumable are provided with identification codes for the identification module 40 to scan, such as bar codes, two-dimensional codes, FRID and the like, which are used as functions of object information acquisition, experimental database establishment and the like.
The liquid-transferring module 50 can transfer liquid-transferring at a first liquid-transferring speed and uniformly mix liquid-transferring at a second liquid-transferring speed, the first liquid-transferring speed is 1/3 of the second liquid-transferring speed, the liquid-transferring speed and the liquid-transferring speed of the liquid-transferring module 50 can be controlled by adjusting the feeding amount of the liquid-transferring push rod, and when the liquid-transferring module 50 is used for liquid-transferring at the second liquid-transferring speed, the feeding amount of the liquid-transferring push rod is 10 mm/s.
The overlapping period exceeds 50% of the short period of time of the two periods, so that transfer of the sample liquid can be performed faster and more accurately.
The carrier 204 further comprises a sample analysis module, which can be driven by the lower driving unit simultaneously to realize the same displacement. The sample analysis module comprises a temperature circulation module and an optical detection module 310, wherein the temperature circulation module comprises an active heat dissipation part for realizing temperature reduction, the active heat dissipation part comprises a heat dissipation fin 307 and a bottom fan assembly, the heat dissipation fin 307 is connected with the automatic loading area 303, and the bottom fan assembly comprises a bottom fan 308 and an exhaust channel 309; the bottom fan 308 is connected with the exhaust channel 309, and the cooling fin 307 is matched with the exhaust channel 309, so that forced heat dissipation can be performed on the cooling fin 307 through the bottom fan 308, the heat dissipation of the integrated machine can be faster, and the stability of an internal system is ensured.
The carrying platform 204 may be close to or far away from the first ventilation opening 801 under the action of the lower driving unit, for example, a certain interval exists between the carrying platform and the first ventilation opening 801 in the process of sample extraction and purification, and in the process of cyclic amplification operation, the exhaust channel 309 is connected with the first ventilation opening 801, so as to form a relatively sealed first air channel, so that waste heat generated by the amplification thermal cycle in the process of cyclic amplification operation is rapidly discharged out of the equipment housing 301 with little interference to the interior of the integrated machine, and is not leaked into the interior of the housing 301 in the process of discharge to cause waste heat accumulation to affect the working environment such as a circuit, thereby ensuring the reliability of the whole system, and meanwhile, the sample extraction and purification and cyclic amplification can be operated at different positions through the driving of the lower driving unit, thereby maximally ensuring the reliability in the process of performing the complex function operation on the integrated carrying platform, and reducing or even avoiding the pollution generated by aerosol as much as possible.
A second ventilation opening 802 is further provided on the same side of the housing 301 as the first ventilation opening 801, and may be directly or indirectly connected to an independent air duct 8021, and more preferably, a top fan 8022 connected to the independent air duct 8021 may be provided, so that during a period of time between at least part of the carrying platform and the first ventilation opening 801 (for example, during a period of time of sample extraction and purification operation after the consumable material is extracted and opened by the cover body), the second ventilation opening 802 and the connected independent air duct 8021 are in an operation state to realize air discharge in the integrated machine, so that serious aerosol pollution is not generated even if sample extraction and purification operation is completed in a cover opening state, and during a circulation amplification operation, the top fan 8022 is always in an operation state, and risks of mixed cross pollution can be furthest reduced through two air ducts.
A third air vent 803 is further provided on the same side as the first air vent 801, and the third air vent 803 is provided with a middle fan 8031, which can provide heat dissipation, negative pressure, pollution reduction and other functions in other time periods. A second air channel is arranged between the third air port 803 and the bottom fourth air port 804, wherein air flows from the third air port 803 to the fourth air port 804 as a whole.
Other time periods may be sample extraction and purification operation time periods, and the whole operation is performed under the condition that the extraction consumable is opened, so that the possible pollution risk is also larger, and at this time, the cross pollution risk caused by the fact that most areas of the air channels are similar to the air flowing direction can be reduced to the greatest extent through the second air channel separated from the bearing table 204. In this time period, because the first ventilation opening 801 is spaced from the carrying platform 204, the first ventilation opening 801 can also be used as an auxiliary ventilation opening, a smaller amount of air enters the detection device housing 301 from the first ventilation opening 801 under the negative pressure effect generated by the internal flow, so that the air update speed in the device housing 301 is increased as a whole, the region a in fig. 15 can be the extraction consumable part 305 on the carrying platform 204, the region b can be the amplification consumable part 306, under such air channel and air flow conditions, the extraction consumable part 305 is located in the downwind direction of the amplification consumable part 306, so that although the extraction consumable part is required to operate in the uncapping state in the extraction and purification time period, the extraction consumable part 305 is located in the downwind direction position, even if there is a pollution risk, the detection result of the amplification consumable part 306 in the upwind direction is not affected, so that the final obtained result in the whole detection device is more accurate and reliable, a fourth air channel can be formed between the first ventilation opening 801 and the fourth air channel 804 in the fourth overall air flow direction in the time period under the negative pressure effect. Naturally, in order to achieve the above effect, the fan may be disposed at the fourth air port 804 located at the bottom of the housing 301.
Other time periods can be circulation amplification time periods, the lower driving unit drives the bearing table 204 to be connected with the first ventilation opening 801, at the moment, waste heat generated in the thermal circulation process under the action of the bottom fan 308 can be rapidly discharged out of the shell 301 through a relatively closed first air duct formed by abutting, air carrying waste heat in the air duct can minimally influence the internal environment of the detection equipment, and the detection device has important significance for reliable operation of the circuit electric control device, and meanwhile, the waste heat generated by circuit elements and the like can be rapidly discharged on the one hand and the internal pollution risk can be reduced on the other hand by establishing the air flow direction as a third air duct which is directed to the third ventilation opening 803 by the fourth ventilation opening 804. Meanwhile, the first air channel and the third air channel have basically consistent outflow directions, so that the risk of certain cross contamination caused by turbulent turbulence, turbulence and the like due to large difference of the flow directions can be reduced. Of course, the fourth air port 804 may also be located at the top of the housing 301, so that the effect achieved is similar to that of the bottom, and the detailed description is omitted here. Of course, all or part of the ventilation openings can be provided with HEPA (high efficiency particulate air) filtering components, so that the safety and reliability of the operation of the instrument are ensured by filtering the air flowing in or out, and fans at different ventilation openings can be designed according to parameters such as flow and the like, and the specific number is not limited.
The optical detection module 310 may sequentially detect fluorescent signals of a plurality of fluorescent channels of a plurality of cup-separating holes. The optical detection module 310 is located below the exhaust channel 309, and is in optical communication with the bottom of the amplification product section 306. Since the optical detection module 310 is disposed at a lower position of the air discharge passage 309, the hot air discharged from the air discharge passage 309 does not thermally affect the optical detection module 310 to ensure the reliability of the system. It also allows the entire optical detection module 310 to be combined with the moving automated loading zone 303 to achieve a relatively immobile effect of both locations.
Example 2
As shown in fig. 1 to 17, the control method of the efficient moving integrated machine for sample detection, which is described in embodiment 1, includes the following steps: starting up, the top blower 8022 is running.
Loading configuration: opening and closing part 302, first motor 101 and second motor 201 in the lower driving unit drive automation loading area 303 outside shell 301 in serial operation, sweep the code to the sample tube with the code scanner, obtain the corresponding information of sample tube, load the sample tube in sample tube area 304, draw consumable in the consumable area 305 loading and draw consumable, expand consumable in consumable area 306 loading, after the loading is accomplished, first motor 101 and second motor 201 drive automation loading area 303 in serial operation returns in shell 301, closes opening and closing part 302.
Scanning code identification: the upper driving unit drives the identification module 40 to move in a first time period, the lower driving unit drives the bearing table 204 to move in a second time period, the first time period and the second time period are at least partially overlapped, the identification module 40 respectively performs code scanning identification on the extracted consumable and the amplified consumable, wherein when the upper driving unit and the lower driving unit are simultaneously driven, the consumable identification camera of the identification module 40 performs dynamic code scanning, and when the upper driving unit is independently driven, the consumable identification camera of the identification module 40 performs static code scanning.
Uncapping the sample tube: the lifting assembly operates to enable the sample tube cover opening and closing mechanism 20 to descend to a position corresponding to the target sample tube, the cover rotating assembly rotates anticlockwise, the rotating head is screwed with the container cover, the cover rotating assembly continues to rotate anticlockwise, the container cover is driven to rotate anticlockwise, the container cover is unscrewed, and the cover rotating assembly ascends.
Extracting consumable material and uncovering: the extraction consumable switching cover mechanism 30 opens the extraction consumable.
Sample liquid transferring step: the upper driving unit drives the pipetting module 50 to move in a first time period, the lower driving unit drives the bearing table 204 to move in a second time period, the first time period and the second time period at least partially overlap, and the upper driving unit and the lower driving unit cooperate with each other to drive the pipetting module 50 to move between the sample tube and the splitting hole site of the extracting consumable to perform a sample liquid transferring operation. Closing a sample tube cover: the lifting assembly operates to enable the sample tube cover opening and closing mechanism 20 to descend to a position corresponding to the target sample tube, the cover screwing assembly rotates clockwise to drive the container cover to rotate clockwise, the container cover is screwed on the container body, the cover screwing assembly continues to rotate clockwise, the rotating head is separated from the container cover, and the cover screwing assembly ascends.
Sample extraction and purification steps: the upper driving unit drives the extraction module 60 to move in a first time period, the lower driving unit drives the bearing table 204 to move in a second time period, the first time period and the second time period at least partially overlap, and the upper driving unit and the lower driving unit cooperate with each other to drive the extraction module 60 to move between all hole sites of the extraction consumable to perform sample extraction and purification operations.
And (3) a consumable material cover opening step: the amplification consumable switching cover mechanism 70 opens the amplification consumable.
And (3) an amplification system establishment step: the upper driving unit drives the pipetting module 50 to move in the first time period, the lower driving unit drives the bearing table 204 to move in the second time period, the first time period and the second time period are at least partially overlapped, the upper driving unit and the lower driving unit mutually cooperate to drive the pipetting module 50 to move between the eluting hole site of the extracting consumable and the premixing hole site of the amplifying consumable to perform eluent transfer operation, the pipetting module 50 performs n times of mixing operation on the premixing hole site, n is a positive integer, the mixing operation is that the pipetting module 50 absorbs the eluent in the eluting hole site and then discharges the eluent into the premixing hole site, after the eluent is mixed with the freeze-drying reagent, the upper driving unit and the lower driving unit mutually cooperate to drive the pipetting module 50 to perform solution distribution operation between the hole sites of the amplifying consumable, the pipetting module 50 sequentially transfers the mixed premix into the sub-cup hole site in a multi-absorption multi-row mode, the accurate multi-row liquid absorption scheme is adopted in this place to enable the premix liquid amount in each sub-cup to be more consistent, after the premix liquid distribution is completed, the liquid absorption multi-row liquid absorption hole site is adopted to transfer from the liquid absorption liquid seal hole site to each sub-cup to a position, the liquid amount in the liquid seal hole site is not transferred to the liquid seal position is not enough to be 2-phase, the problem of the liquid seal is solved, the liquid is not fully is solved, and the problem of the volume of the liquid seal is not being fully can be solved is avoided, and the problem of the volume is not is solved, and the problem of the sufficient is solved, and the quality is not is solved, and the problem is not is solved, and the sufficient is due to the good to the quality is due to the liquid transfer in the liquid transfer can is well and the liquid can is not and can and is not fully and can be well and is well and can and is well and is not affected.
And (3) extracting consumable material and closing the cover: the extraction consumable switching cover mechanism 30 closes the extraction consumable.
Closing the cover of the amplification consumable: the amplification consumable switching cover mechanism 70 closes the amplification consumable.
And (3) a cyclic amplification step: and the middle fan operates, the temperature circulation module is started, and PCR thermal circulation amplification is executed.
The analysis step: and outputting a sample fragment analysis result based on a fluorescence analysis method.
In the amplification system establishment step, the pipetting module 50 transfers the eluent from the elution hole site of the extraction consumable to the premixing hole site of the amplification consumable in two times, the first pipetting module 50 transfers the first volume of eluent into the premixing hole site, so that the freeze-drying reagent in the premixing hole site is dissolved, sufficient space in the premixing hole site is ensured, and the second pipetting module 50 transfers the second volume of eluent into the premixing hole site, wherein the first volume of eluent is 0.2-0.9 of the second volume of eluent. The eluent is transferred twice, so that the eluent overflow caused by the fact that the freeze-dried reagent cannot be dissolved immediately can be avoided.
In the amplification system establishment step, the pipetting module 50 transfers and drains liquid at a first liquid drain speed in the pipetting process and mixes and drains liquid at a second liquid drain speed in the mixing operation, wherein the first liquid drain speed is 1/4-1/2 of the second liquid drain speed, so that more sufficient mixing can be realized, the effect of micro bubbles which can influence the test result can not be generated, and the problem that the wall hanging phenomenon is serious possibly to cause a false negative test result due to too fast liquid drain in the pipetting process can be avoided.
In the cyclic amplification step, the lower driving unit drives the carrying table 204 to move towards the first ventilation opening 801 until the air exhaust channel 309 is connected with the first ventilation opening 801 to form a relatively sealed first air channel, and the cooling fin 307 and the bottom fan 308 are started to cool the amplification consumable part area. At the same time, the middle blower 8031 is started, and a third air channel with the air flow direction pointing from the fourth air port 804 to the third air port 803 is established.
In the analysis step, the principle of the fluorescence analysis method is as disclosed in application number CN201610152466.2, and the multi-fluorescence channel detection system for real-time fluorescence quantitative PCR comprises a fluorescence detection unit, an optical fiber tray and a turntable, wherein the fluorescence detection unit comprises a light source, an excitation filter, a dichroic mirror, an optical fiber coupling lens, an optical fiber, a detection filter and a photoelectric sensor, the dichroic mirror combines the existing excitation unit and the detection unit into a whole, light emitted by the light source is sequentially filtered by the excitation filter and the optical fiber coupling lens, finally fluorescent materials of a sample in an excitation test tube are injected into the test tube through the optical fiber to generate fluorescence, a part of fluorescence is sequentially returned to the optical fiber coupling lens from the optical fiber to be collimated, the detection filter filters pure fluorescence, and finally the fluorescence is injected into the photoelectric sensor to perform photoelectric conversion; the optical fiber disc is inserted with a plurality of optical fibers, a plurality of fluorescence detection units are distributed on the optical fiber disc, and the optical fiber disc rotates around the optical fiber disc center for one circle, so that fluorescence signals of a plurality of fluorescent channels of a plurality of test tube hole sites can be sequentially detected.
Fig. 17 illustrates a control module diagram of an all-in-one machine of the present invention, where the driving module is divided into 3 sub-driving modules, namely, a first sub-driving module, a second sub-driving module and a third sub-driving module, for realizing low-cost and high-efficiency control of the all-in-one machine of the present invention. Each sub-driving module CAN be in information communication with the core board through a connection mode of the CAN bus, each sub-driving module CAN be in information communication with the core board through any public query response mechanism to acquire a control instruction converted by the core board through the core board conversion board, the control instruction CAN be transmitted in a function or form and the like without limitation, the core board CAN be connected to the exchange machine and the industrial personal computer through a LAN connection mode, the industrial personal computer CAN be connected to the PC end through the LAN connection mode to form remote control and also connected to the touch screen to receive and edit touch screen information, and of course, the industrial personal computer CAN realize multiple parallel connection through a wired or wireless mode and also CAN be connected with the USB to carry out version upgrading and the like. Each sub-driving module can control the operation of different units to be driven according to the control instruction transmitted by the core board, the upper driving unit of the driving combination module and the lower driving unit of the driving bearing table are optimally configured in two different sub-driving modules, so that the two sub-driving modules can execute the control instruction transmitted by the core board in parallel, the driving instruction of the upper driving unit and the driving instruction of the lower driving unit can be simultaneously output in an overlapped time period, complex control coordination under the configuration of a clock circuit is not needed between the two sub-driving modules, and the two sub-driving modules in the configuration only need to independently arrange driving time sequences according to the clock circuits in the control instructions respectively, so that the control is more efficient. The invention also comprises a plurality of displacement sensors, so that the calibration of different mechanisms can be executed, accurate reference can be provided for accurate displacement control, and whether the integrated machine correctly executes the control instruction sent by the core board or not can be judged in a matched manner, and the final state can be timely feedback controlled.
Table 1 shows the results of 8 repeated sample multiplex detection and verification performed by the integrated machine according to the present invention, and as can be seen from the results in Table 1, the integrated machine according to the present invention reduces the consumable exposure time due to the scheme of matching the upper driving unit with the lower driving unit, and can efficiently and stably obtain multiple detection results, and the unique arrangement of consumable hole sites according to the present invention can reduce the possibility of intersecting the liquid separation paths of the sample liquid transfer, extraction and eluent transfer machine PCR premix, and further can obtain efficient and stable detection results, and the deviation of the results obtained by performing 8 times of detection on different targets by using the integrated machine according to the present invention is relatively small. The small STD and CV values indicate that the integrated machine has reasonable design layout, can be less polluted to influence experimental results, and has high reproducibility of the experimental results.
Table 1 the result of the repeated verification of the sample multiplex detection performed by the all-in-one machine of the present invention
The principles and embodiments of the present invention have been described herein with reference to specific examples, which are intended to be merely illustrative of the methods of the present invention and their core ideas. It should be noted that it will be apparent to those skilled in the art that various modifications and adaptations of the invention can be made without departing from the principles of the invention and these modifications and adaptations are intended to be within the scope of the invention as defined in the following claims.
In the description of the present invention, it should be noted that, directions or positional relationships indicated by terms such as "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc., are directions or positional relationships based on those shown in the drawings, or are directions or positional relationships conventionally put in use of the inventive product, are merely for convenience of describing the present invention and simplifying the description, and are not indicative or implying that the apparatus or element to be referred to must have a specific direction, be constructed and operated in a specific direction, and thus should not be construed as limiting the present invention.
In the description of the present invention, it should also be noted that, unless explicitly specified and limited otherwise, the terms "disposed," "mounted," "connected," and "connected" are to be construed broadly, and may be, for example, fixedly connected, detachably connected, or integrally connected; can be mechanically or electrically connected; can be directly connected or indirectly connected through an intermediate medium, and can be communication between two elements. The specific meaning of the above terms in the present invention will be understood in specific cases by those of ordinary skill in the art.

Claims (10)

1. An efficient mobile sample detection all-in-one machine is characterized by comprising an upper area and a lower area; the upper region comprises an upper driving unit and a combined module, the upper driving unit can drive the combined module to horizontally move, and the combined module comprises a pipetting module and an extraction module; the lower region comprises a lower driving unit and a bearing table, the bearing table comprises a sample tube region, an extraction consumable region and an amplification consumable region, and the lower driving unit can drive the bearing table to move horizontally; the time period that upper portion drive unit drive combination module moved is the first time period, the time period that lower part drive unit drive plummer moved is the second time period, there is overlap time period between first time period and the second time period, upper portion drive unit and lower part drive unit mutually support for the pipetting module can move and carry out sample liquid transfer operation, the pipetting module can move and carry out sample extraction purification operation in the pipetting consumable, the pipetting module can move and carry out eluent transfer operation, pipetting module can move and carry out solution distribution operation in the amplification consumable in the region of the pipetting consumable between the region of the pipetting consumable and the amplification consumable.
2. The mobile sample testing integrated machine according to claim 1, wherein the upper driving unit drives the combining module with a first precision, the combining module moves horizontally at a first speed under the action of the upper driving unit, the lower driving unit drives the carrying platform to move horizontally at a second precision, the carrying platform moves horizontally at a second speed under the action of the lower driving unit, the first precision is higher than the second precision and the first speed is lower than the second speed, or the first precision is lower than the second precision and the first speed is higher than the second speed.
3. The mobile sample testing integrated machine according to claim 1, wherein the lower driving unit comprises a first motor and a second motor, the first motor can drive the carrying platform to move within a first movement distance, the second motor can drive the carrying platform to move within a second movement distance, and the first motor and the second motor cooperate with each other so that the movement distance of the carrying platform does not exceed the sum of the first movement distance and the second movement distance; the first motor and the second motor can be matched with each other to drive the bearing table to carry out loading configuration operation outside the shell; the first motor and the second motor work in series.
4. The mobile, efficient, sample testing all-in-one machine of claim 1, wherein the combination module further comprises an identification module, the upper drive unit being cooperable with the lower drive unit such that a first period of time for movement of a corresponding identification module at least partially overlaps a second period of time for movement of a corresponding carrier; the consumable identification camera of the identification module can execute dynamic code scanning identification or static code scanning identification.
5. The mobile, efficient sample testing all-in-one machine of claim 1, wherein said pipetting module is capable of transferring liquid at a first liquid drain rate and mixing liquid at a second liquid drain rate, said first liquid drain rate being 1/4-1/2 of said second liquid drain rate.
6. A control method of an efficient moving integrated machine for sample detection, which adopts the efficient moving integrated machine for sample detection according to any one of claims 1 to 5, characterized by comprising the steps of,
sample liquid transferring step: the upper driving unit drives the pipetting module to move in a first time period, the lower driving unit drives the bearing table to move in a second time period, the first time period and the second time period are at least partially overlapped, and the upper driving unit and the lower driving unit are matched with each other to drive the pipetting module to move between the sample tube and the cracking hole site of the extraction consumable to execute sample liquid transferring operation;
Sample extraction and purification steps: the upper driving unit drives the extraction module to move in a first time period, the lower driving unit drives the bearing table to move in a second time period, the first time period and the second time period are at least partially overlapped, and the upper driving unit and the lower driving unit are mutually matched to drive the extraction module to move between all hole sites of the extraction consumable to perform sample extraction and purification operation;
and (3) an amplification system establishment step: the upper driving unit drives the pipetting module to move in a first time period, the lower driving unit drives the bearing table to move in a second time period, the first time period and the second time period are at least partially overlapped, the upper driving unit and the lower driving unit mutually cooperate to drive the pipetting module to move between an elution hole site for extracting consumable materials and a premixing hole site for amplifying the consumable materials to perform eluent transfer operation, the pipetting module performs n times of mixing operation on the premixing hole site, n is a positive integer, the mixing operation is that the pipetting module absorbs eluent in the elution hole site, then the eluent is discharged into the premixing hole site, and after the eluent is mixed with freeze-drying reagent, the upper driving unit and the lower driving unit mutually cooperate to drive the pipetting module to move between each hole site for amplifying the consumable materials to perform solution distribution operation.
7. The method according to claim 6, wherein in the step of creating the amplification system, the pipetting module transfers the eluent from the eluting hole of the extraction consumable to the pre-mixing hole of the amplification consumable m times, m being an integer of 2 or more.
8. The method according to claim 6, wherein in the amplification system creation step, the pipetting module transfers the liquid at a first liquid discharge speed during pipetting and mixes the liquid at a second liquid discharge speed during mixing, the first liquid discharge speed being 1/4 to 1/2 of the second liquid discharge speed.
9. The method of controlling an integrated machine for efficiently moving sample testing according to claim 6, further comprising, before said step of transferring the sample liquid
Loading configuration: the first motor and the second motor in the lower driving unit work in series to drive the bearing table to be outside the shell, the sample tube is loaded in the sample tube region, the extracting consumable is loaded in the extracting consumable region, the amplifying consumable is loaded in the amplifying consumable region, and after loading is completed, the first motor and the second motor work in series to drive the bearing table to return to the shell.
10. The method for controlling an efficient moving integrated machine for sample detection according to claim 6, further comprising, after said loading and configuring step
Scanning code identification: the upper driving unit drives the identification module to move in a first time period, the lower driving unit drives the bearing table to move in a second time period, the first time period and the second time period are at least partially overlapped, the identification module respectively scans and identifies the extracted consumable and the amplified consumable, wherein when the upper driving unit and the lower driving unit are simultaneously driven, the consumable identification camera of the identification module performs dynamic code scanning, and when the upper driving unit is independently driven, the consumable identification camera of the identification module performs static code scanning.
CN202311063582.3A 2023-08-22 2023-08-22 Efficient moving integrated machine for sample detection and control method thereof Pending CN117126729A (en)

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Application Number Priority Date Filing Date Title
CN202311063582.3A CN117126729A (en) 2023-08-22 2023-08-22 Efficient moving integrated machine for sample detection and control method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202311063582.3A CN117126729A (en) 2023-08-22 2023-08-22 Efficient moving integrated machine for sample detection and control method thereof

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CN117126729A true CN117126729A (en) 2023-11-28

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