CN114940943B - PCR instrument - Google Patents

Abstract

The application provides a PCR instrument, which comprises an amplification device and an optical detection device. The amplification device comprises: a sample accommodating unit including a sample bin tray movable between a delivery position and an amplification detection position; an amplification unit movable in a vertical direction between a raised position and a lowered position; the optical fiber fixing component is provided with an optical fiber fixing hole. The detection device includes: a base provided with a through hole; one end of each optical fiber corresponds to one through hole, and the other end of each optical fiber is fixed in the corresponding optical fiber fixing hole; the turntable is sleeved on the output shaft of the driving piece; at least one optical device, fixed to the carousel, comprising an excitation light generation module, a transmission light reception module and a Y-shaped optical fiber, the first ends of the central and peripheral optical fibers comprised in the Y-shaped optical fiber being constrained together and adapted to be aligned in succession with each through hole when the carousel rotates, one of the light generation module and the light reception module being connected to the second end of the central optical fiber and the other to the second end of the peripheral optical fiber.

Description

PCR instrument

Technical Field

The application relates to the field of PCR instruments, in particular to a PCR instrument.

Background

The Polymerase Chain Reaction (PCR) is a molecular biology technique for amplifying and amplifying specific DNA fragments, and can be regarded as special DNA replication in vitro, and the biggest characteristic of the PCR is that trace amount of DNA can be greatly increased. A PCR instrument (also referred to as a gene amplification instrument) is used to carry out such reactions.

In a PCR instrument, it is usually necessary to perform gene amplification on a plurality of samples to be detected simultaneously in parallel, and then perform fluorescence detection on the samples to be detected in the reaction consumables by using a fluorescence detection module. The fluorescence detection module can include one or more detection channels (also referred to as fluorescence channels) for detecting one or more target genes of interest in a sample to be tested. If a plurality of target genes to be detected exist in a sample to be detected, a plurality of fluorescence channels are needed to work, and if only one target gene to be detected needs to be detected, only one fluorescence channel is needed to work. The conventional fluorescence detection module has low detection efficiency and low detection precision.

In addition, the traditional PCR instrument has the problems that the structure of a sample accommodating mechanism is complex, the assembly difficulty is high, the maintenance is difficult, the detection accuracy is influenced due to the uneven heating of an amplification unit, the optical fiber is easy to age and damage after long-time use, the assembly accuracy is reduced, and the like, and the reliability and the user experience of the PCR instrument are seriously influenced.

Disclosure of Invention

It is an object of the present application to provide a PCR instrument that at least partially addresses the above-mentioned problems and/or other potential problems found in conventional PCR instruments.

In one aspect of the present application, a PCR instrument is provided that includes an amplification device and an optical detection device. The amplification device comprises: the sample accommodating unit comprises a sample bin tray for accommodating a plurality of samples to be detected, and the sample bin tray is suitable for moving between a delivery position and an amplification detection position; an amplification unit movable in a vertical direction between a raised position in which the amplification unit is adapted to perform temperature adjustment on the plurality of samples to be tested and a lowered position in which the amplification unit is detached from the plurality of samples to be tested; and the optical fiber fixing component is arranged at the top of the sample accommodating unit and comprises an optical fiber fixing plate, and a plurality of optical fiber fixing holes aligned with the plurality of samples to be tested in the vertical direction are formed in the optical fiber fixing plate. The optical detection device includes: a base having a set of through holes formed therein; a plurality of guide optical fibers, one end of each guide optical fiber being disposed at the first side of the base corresponding to one of the set of through holes, and the other end of each guide optical fiber being fixed in a corresponding optical fiber fixing hole on the optical fiber fixing plate; the turntable is positioned on the second side of the base and is sleeved on the output shaft of the driving piece; and at least one optical device disposed on the turntable, each optical device comprising an excitation light generation module, a transmission light receiving module, and a Y-shaped optical fiber, the Y-shaped optical fiber comprising a central optical fiber and at least one circumferential optical fiber, first ends of the central optical fiber and the at least one circumferential optical fiber being tethered together and adapted to be sequentially aligned with each through-hole of the set of through-holes upon rotation of the turntable, a second end of the central optical fiber being connected to one of the excitation light generation module and the transmission light receiving module, a second end of the at least one circumferential optical fiber being connected to the other of the excitation light generation module and the transmission light receiving module, the excitation light generation module being configured to generate excitation light and pass the excitation light through the Y-shaped optical fiber, a respective through-hole of the set of through-holes aligned with the first end of the Y-shaped optical fiber, and a Y-shaped optical fiber, And the corresponding guide optical fibers arranged corresponding to the corresponding through holes in the plurality of guide optical fibers irradiate the corresponding samples to be tested, and the emission light receiving module is configured to receive the emission light emitted by the irradiated samples to be tested through the corresponding guide optical fibers in the plurality of guide optical fibers, the corresponding through holes in the group of through holes and the Y-shaped optical fibers.

In some embodiments, the amplification apparatus further comprises a first rack, and the sample-accommodating unit and the amplification unit are respectively movably disposed on the first rack.

In some embodiments, the amplification apparatus further comprises a lift drive assembly coupled to the amplification unit and comprising a lift drive and a pair of transmission linkage assemblies, the lift drive driving the amplification unit to move between the raised position and the lowered position via the pair of transmission linkage assemblies, each transmission linkage assembly of the pair of transmission linkage assemblies comprising: a driving wheel coupled to the elevation driving part to be rotated by the elevation driving part, and including an eccentrically disposed pivot shaft; a first link including a first end and a second end rotatably disposed on the first bracket; a drive link rotatably connected between the pivot shaft and the first end of the first link; a second link including a first end and a second end, the first end of the second link being rotatably connected to the first end of the first link, the second end of the second link being rotatably connected to the amplification unit; and a chute mechanism fixedly disposed on the first bracket and including a chute disposed in the vertical direction for the second end of the second link to slide therein.

In some embodiments, the sample-holding unit further comprises: a sample compartment holding tray fixedly disposed on the first rack and including a bottom wall and a pair of side walls, the bottom wall including an opening; and a translation drive assembly coupled to the sample bin tray to drive the sample bin tray to move along the sidewall.

In some embodiments, the translation drive assembly comprises: a rack disposed on the sample bin tray and moving with the sample bin tray; a gear disposed on the first rack or the sample compartment holding tray and engaged with the rack, and an axis of the gear extends in the vertical direction; and a translation drive including an output shaft coupled to the gear to drive the gear to rotate.

In some embodiments, the sample-holding unit further comprises: a guide strip disposed on the bottom wall of the sample compartment holding tray at a predetermined distance from the side wall; and a guide slot formed on the sample bin tray and adapted for the guide strip to be slidably disposed therein to provide a guide for movement of the sample bin tray.

In some embodiments, the sample-holding unit further comprises: a retention strip formed on the sidewall spaced a predetermined distance from the bottom wall, the retention strip adapted to retain at least a portion of the sample bin tray between the retention strip and the bottom wall.

In some embodiments, the lift drive assembly further comprises: a first sensor assembly coupled to at least one of the sample cartridge holding tray and the amplification unit and adapted to detect a position of the amplification unit relative to the sample cartridge holding tray.

In some embodiments, the translation drive assembly further comprises: a second sensor assembly coupled to at least one of the sample cartridge fixed disk and the sample cartridge tray and adapted to detect a position of the sample cartridge tray relative to the sample cartridge fixed disk.

In some embodiments, the amplification unit comprises: a temperature control assembly comprising a plurality of reaction chambers and arranged to align with the opening when the sample compartment tray is in the amplification detection position, such that the amplification unit supports the sample to be tested when in the raised position and temperature conditions the sample to be tested in a controlled manner; and a heat dissipation assembly thermally coupled to the temperature control assembly and including a heat dissipation body, heat dissipation fins arranged on the heat dissipation body, and a fan coupled to the heat dissipation fins and adapted to flow air in a predetermined direction in the heat dissipation fins to dissipate heat from the heat dissipation body.

In some embodiments, the temperature control assembly further comprises a heat dissipation air duct, the heat dissipation air duct comprising: a pair of mounting walls provided at least outside the heat dissipating fins in parallel with the extending direction of the heat dissipating fins; and an end wall connecting the pair of mounting walls and disposed at a distal end of the heat dissipating fin, the end wall having an air inlet, wherein the fan is coupled to the end wall and aligned with the air inlet such that the air enters from the air inlet and exits from two air outlet ports in an extending direction of the heat dissipating fin in the extending direction of the heat dissipating fin.

In some embodiments, the heat dissipation assembly further comprises: at least one heat pipe disposed in the heat sink adjacent to the plurality of reaction chambers.

In some embodiments, the fiber securing assembly further comprises: a thermostatic cover disposed on a side of the optical fiber fixing plate adjacent to the sample to be measured and having a plurality of through holes aligned with the plurality of optical fiber fixing holes in the vertical direction; a thermal insulation plate fixed to the optical fiber fixing plate and located between the optical fiber fixing plate and the constant temperature cover, the thermal insulation plate having a plurality of mounting holes aligned with the plurality of optical fiber fixing holes in the vertical direction; and a plurality of lenses, each fixed into a corresponding one of the mounting holes and located between the other end of the guiding fiber and the thermostatic cover, at least for collimating the excitation light and the emission light.

In some embodiments, the second end of the central optical fiber is connected to the excitation light generation module, the second end of the at least one circumferential optical fiber is connected to the emission light receiving module, the central optical fiber has a diameter a, the first end of the Y-shaped optical fiber has a diameter b, each of the plurality of guiding optical fibers has a diameter c, wherein the diameter a, the diameter b, and the diameter c satisfy the following relationship: b > c > a.

In some embodiments, the central fiber has a divergence angle α, each of the plurality of guiding fibers has a divergence angle β, each of the plurality of guiding fibers has a separation distance d with the first end of the Y-fiber aligned, wherein the divergence angle α, the divergence angle β, the separation distance d and the diameter a, the diameter b, the diameter c satisfy the following relationship:

，

。

in some embodiments, the excitation light generation module comprises a light source configured to emit excitation light, a first convex lens configured to condense the excitation light emitted by the light source, a second convex lens configured to condense the light from the first convex lens into parallel light, an excitation light filter configured to filter the parallel light, and a third convex lens configured to condense the filtered parallel light to the second end of the central optical fiber.

In some embodiments, the emission light receiving module includes a fluorescence signal receiver, a fourth convex lens, an emission light filter, a fifth convex lens, and a sixth convex lens, the sixth convex lens is configured to receive the emission light from the second end of the at least one circumferential optical fiber and to converge the emission light, the fifth convex lens is configured to converge the light from the sixth convex lens into parallel light, the emission light filter is configured to filter the parallel light, and the fourth convex lens is configured to converge the filtered parallel light to the fluorescence signal receiver.

In an embodiment according to the application, the driving member of the optical detection apparatus may drive the turntable to rotate, so as to drive the specific optical device on the turntable to rotate to a position corresponding to the through hole on the substrate, so that the first end of the Y-shaped optical fiber is sequentially aligned with each through hole on the substrate. Under the condition that the first end of the Y-shaped optical fiber is aligned with each through hole in the base, the exciting light generating module can enable the exciting light to irradiate the corresponding sample to be detected on the sample bin tray through the Y-shaped optical fiber, the corresponding through hole in the base and the corresponding guide optical fiber correspondingly arranged with the corresponding through hole, and the emission light receiving module can receive emission light emitted by the irradiated sample to be detected on the sample bin tray through the corresponding guide optical fiber, the corresponding through hole and the Y-shaped optical fiber. In this way, continuous fluorescence detection of a plurality of samples to be detected can be realized, which can improve the fluorescence detection efficiency of the PCR instrument on one hand and improve the fluorescence detection precision of the PCR instrument on the other hand.

In addition, in the embodiment according to the application, the structure of the delivery part of the amplification device of the PCR instrument can be obviously simplified by utilizing the cooperation of delivery and lifting of the sample accommodating unit and the amplification unit, and the delivery of the sample to be detected is convenient only by delivering the sample bin tray. In this way, the structure of the PCR instrument can be simplified, the assembly difficulty can be reduced, and the assembly efficiency can be improved.

It should be understood that what is described in this section is not intended to limit key or essential features of embodiments of the application, nor is it intended to limit the scope of the application. Other features of the present application will become apparent from the following description.

Drawings

The above and other features, advantages and aspects of various embodiments of the present application will become more apparent by referring to the following detailed description when taken in conjunction with the accompanying drawings. In the drawings, like or similar reference characters designate like or similar elements, and wherein:

FIGS. 1 and 2 show schematic external structural views of a PCR instrument according to an embodiment of the present application;

FIG. 3 is a schematic diagram showing the internal structure of a PCR instrument according to an embodiment of the present application;

FIG. 4 shows a schematic structural diagram of an amplification apparatus according to an embodiment of the present application;

FIG. 5 shows a schematic structural view of an amplification apparatus according to an embodiment of the present application, in which a part of the top is removed in order to show the internal structure;

FIG. 6 shows a schematic view of an amplification apparatus according to an embodiment of the present application, viewed from another angle;

FIG. 7 shows a schematic structural view of an amplification apparatus according to one embodiment of the present application, with a sample compartment tray in an amplification detection position;

FIG. 8 shows a schematic structural view of a sample-holding unit according to an embodiment of the present application, wherein the sample bin tray is in an amplification detection position;

FIG. 9 shows a schematic structural view of a sample-holding unit according to an embodiment of the present application, with the sample bin tray in a shipping position;

FIGS. 10 to 13 are schematic views showing the structure of an amplification apparatus viewed from different angles according to an embodiment of the present application;

FIG. 14 shows a schematic flow diagram of a method of controlling a PCR instrument according to one embodiment of the present application;

FIG. 15 shows a partial cross-sectional view of an amplification device according to one embodiment of the present application;

FIG. 16 shows a schematic structural diagram of a temperature control module according to an embodiment of the present application;

FIG. 17 shows a schematic layout of an optical detection apparatus according to an embodiment of the present application;

FIG. 18 shows a schematic structural diagram of an optical detection device according to an embodiment of the present application;

FIG. 19 shows a schematic structural diagram of an optical device according to an embodiment of the present application;

FIG. 20 shows a schematic of a Y-fiber configuration according to one embodiment of the present application;

FIG. 21 shows a schematic of a first end of a Y-shaped optical fiber according to one embodiment of the present application;

FIG. 22 shows the relative arrangement with the first end of the Y-shaped optical fiber aligned with the guide optical fiber according to one embodiment of the present application;

FIG. 23 shows a schematic structural diagram of an excitation light generation module according to one embodiment of the present application;

FIG. 24 is a schematic diagram of an architecture of an optical transceiver module according to an embodiment of the present application;

FIG. 25 shows a schematic structural diagram of a conductive slip ring according to an embodiment of the present application;

FIG. 26 shows a schematic structural diagram of an optical detection device according to an embodiment of the present application;

FIG. 27 shows a schematic structural diagram of an optical detection apparatus according to an embodiment of the present application;

fig. 28 shows a partially enlarged schematic view of a portion marked by a circle in fig. 27.

Detailed Description

Preferred embodiments of the present application will be described in more detail below with reference to the accompanying drawings. While the preferred embodiments of the present application are shown in the drawings, it should be understood that the present application may be embodied in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art.

The term "include" and variations thereof as used herein is meant to be inclusive in an open-ended manner, i.e., "including but not limited to". Unless specifically stated otherwise, the term "or" means "and/or". The term "based on" means "based at least in part on". The terms "one example embodiment" and "one embodiment" mean "at least one example embodiment". The term "another embodiment" means "at least one additional embodiment". The terms "first," "second," and the like may refer to different or the same objects.

The PCR instrument is an instrument for realizing the purposes of nucleic acid detection, molecular cloning, gene expression analysis, genotyping, sequencing, mutation and the like by carrying out in-vitro amplification on a specific DNA fragment by utilizing a PCR technology. Specifically, a common PCR instrument mainly provides a suitable temperature environment for in vitro amplification of a specific DNA fragment, and firstly denatures the DNA fragment at a high temperature (usually about 90 ℃ to 95 ℃, also referred to as denaturation temperature) in vitro, opens a double strand to become a single strand, further combines the single strand and a primer at a low temperature (usually about 40 ℃ to 60 ℃, also referred to as renaturation temperature) according to the base complementary pairing principle, and finally adjusts the temperature to an optimal reaction temperature (70 ℃ to 75 ℃, also referred to as extension temperature) of DNA polymerase, and completes synthesis of the single strand with the help of the DNA polymerase and the base to form a complementary strand. The common PCR instrument is actually a temperature control device, and can be well controlled among denaturation temperature, renaturation temperature and extension temperature.

Currently, some PCR instruments are capable of amplifying multiple samples simultaneously. These samples are typically arranged in an m x n array (e.g., a 12 x 8 array) in a sample holding mechanism of the PCR machine. The reaction chamber for temperature regulation of the plurality of samples may be part of the sample holding mechanism, or may be separate from the sample holding mechanism but capable of cooperating with the sample holding mechanism to control the plurality of samples between a denaturation temperature, a renaturation (annealing) temperature, and an extension temperature. The PCR instrument for multi-sample detection can efficiently complete the amplification of a plurality of samples. In addition, there are also PCR instruments (e.g., fluorescent quantitative PCR instruments) that can perform detection while amplifying. Generally, the excitation light generating module for detecting the sample to be detected irradiates on the top or bottom of the sample to be detected, so as to excite the sample to be detected to emit fluorescence. The fluorescence emitted by the excited sample to be detected can be received and processed by the emission light receiving module, and then the qualitative result and the quantitative result of the detection can be output.

However, the conventional PCR instrument with detection function has the problems of complex structure of the sample accommodating mechanism, high assembly difficulty, difficulty in maintenance and the like due to the matching relationship between the detection function and the amplification function. In addition, the conventional PCR instrument with detection function has low detection efficiency and low detection accuracy. In addition, when the traditional amplification equipment is used for amplifying a plurality of samples to be detected, the amplification unit has a larger temperature gradient, so that the problem that the detection accuracy is influenced due to inconsistent amplification of the plurality of samples to be detected caused by nonuniform heating exists. In addition, for the detection of light transmission by using an optical fiber, a glass optical fiber is often used in consideration of the influence of a high-temperature component on the optical fiber, thereby causing high cost. Even so, the high temperature component affects the fitting accuracy between the optical fiber and the optical fiber fixing component, and ultimately affects the measurement accuracy.

Embodiments in accordance with the present application provide a PCR instrument to address, or at least partially address, the above-mentioned problems, or other potential problems, that exist with conventional PCR instruments. Hereinafter, a PCR instrument according to an embodiment of the present application will be described with reference to the accompanying drawings. Fig. 1 and 2 are schematic views showing an external structure of a PCR instrument according to an embodiment of the present application when viewed from different angles, and fig. 3 is a schematic view showing an internal structure of a PCR instrument according to an embodiment of the present application.

As shown in fig. 1 to 3, the PCR instrument described herein generally includes ahousing 900, abase plate 1013, anamplification device 100, anoptical detection device 200, and apower supply device 400. Theamplification apparatus 100, theoptical detection apparatus 200, and thepower supply apparatus 400 are disposed in an internal space formed by thehousing 900 together with thebottom plate 1013. Theamplification apparatus 100 is used for gene amplification of a plurality of samples to be tested. Theoptical detection device 200 is used for performing fluorescence detection on a plurality of samples to be detected. Thepower supply device 400 is used to supply power to theamplification device 100 and theoptical detection device 200. It should be understood that, in some cases, theamplification apparatus 100 and theoptical detection apparatus 200 may be provided with separate power supply apparatuses, and the embodiment of the present application is not limited thereto.

In some embodiments, as shown in fig. 1 and 2, atouch screen 901 is disposed on thehousing 900. Thetouch screen 901 may display various operation states of the PCR instrument, such as the state of theamplification apparatus 100 and the detection result of theoptical detection apparatus 200. In addition, the operator can control and set the PCR instrument through thetouch panel 901.

In some embodiments, as shown in fig. 1 and 2, thehousing 900 is further provided with asample access port 902. The sample compartment tray for holding the sample to be tested is movable between a shipping position and an amplification detection position via asample access port 902, as will be further described below in connection with fig. 4-7.

In some embodiments, as shown in fig. 1 and 2, aheat sink 903 is also provided on thehousing 900. Theheat sink 903 is provided at a position corresponding to theheat sink 1033 on theamplification unit 103, which will be described further below in conjunction with fig. 15.

In some embodiments, as shown in fig. 2 and 3, avent 1014 is also provided in thebottom plate 1013. Thevent 1014 is provided at a position corresponding to theamplification apparatus 100, which will be described further below in conjunction with fig. 15.

As shown in FIG. 3, aguide fiber 22 is provided between theamplification apparatus 100 and theoptical detection apparatus 200. Theguide fiber 22 is used to transmit excitation light generated by theoptical detection device 200 to a sample to be tested in theamplification device 100, and transmit emission light (i.e., fluorescence) generated by the sample to be tested in theamplification device 100 to theoptical detection device 200. In fig. 3, in order to clearly show the connection relationship of the guideoptical fiber 22 with theamplification apparatus 100 and theoptical detection apparatus 200, the display of the middle portion of each guideoptical fiber 22 is omitted, and only one portion of the guideoptical fiber 22 located on theamplification apparatus 100 and the other portion located on theoptical detection apparatus 200 are shown. It should be understood, however, that the two portions of the guidingfiber 22 are connected together by an intermediate portion.

Next, an exemplary structure and operation principle of theamplification apparatus 100 will be described first with reference to fig. 4 to 16.

Fig. 4 to 6 show perspective views of theamplification apparatus 100 viewed from different angles, in which thesample bin tray 1021 is in the out-bin position, and a part of the structure of the top of theamplification apparatus 100 in fig. 5 is removed for convenience of illustrating the internal structure. Fig. 7 shows a schematic view of theamplification apparatus 100 with thesample compartment tray 1021 in the amplification detection position, wherein the fiber fixing structure in theamplification apparatus 100 is removed for ease of illustration of the internal structure.

As shown in fig. 4 to 7, in general, theamplification apparatus 100 includes afirst rack 1011, a sample-accommodatingunit 102, anamplification unit 103, an opticalfiber fixing member 104, and alift driving member 105.

In some embodiments, thefirst bracket 1011 may be vertically disposed on thebottom plate 1013. Thefirst bracket 1011 may include a plurality of posts. Thefirst bracket 1011 may be disposed on thebase plate 1013 in any suitable manner including, but not limited to: threaded connections, i.e. each column in thefirst support 1011 is screwed directly into a corresponding hole in thebase 1013; connecting a fastener; welding; or interference fit, etc.

Fig. 4 and 5 show a portion of the guidingfiber 22 connected between theamplification apparatus 100 and theoptical detection apparatus 200, wherein the guidingfiber 22 is shown to be fixed at the end of theamplification apparatus 100 by thefiber fixing member 104. The structure of thefiber securing assembly 104 will be further described below.

Thesample bin tray 1021 is part of thesample receiving unit 102. As mentioned above, fig. 4 to 6 show schematic views of thesample bin tray 1021 in the out-bin position, and fig. 7 shows a schematic view of thesample bin tray 1021 in the amplification detection position. That is, thesample bin tray 1021 is movable between a shipping position and an amplification detection position. Referring to fig. 1 and 2, thesample cartridge tray 1021 is movable between a discharge position and an amplification detection position via a sample inlet/outlet 902 on thehousing 900. Movement of thesample bin tray 1021 between the out-bin position and the amplification detection position may be accomplished using suitable structure. Fig. 4 to 7 show an example of a mechanism for moving thesample bin tray 1021 in and out of the bin.

In the exemplary embodiment shown in fig. 4-7,sample holding unit 102 may include, in addition tosample cartridge tray 1021, a samplecartridge fixing tray 1022 and atranslation drive assembly 1026. Samplecartridge holding tray 1022 is fixedly disposed onfirst support 1011. Sample cartridge fixeddisk 1022 may include abottom wall 1023 and a pair ofside walls 1024 disposed perpendicular tobottom wall 1023. In addition, in some embodiments, samplecartridge retention tray 1022 may also include a back wall perpendicular tobottom wall 1023 between a pair ofside walls 1024, as shown in fig. 5. Thesample bin tray 1021 is relatively movably disposed in the sample bin fixedtray 1022 along a pair ofside walls 1024 and is accessible from an entrance opposite the rear wall. Atranslation drive assembly 1026 is coupled to samplecompartment tray 1021 to drive movement ofsample compartment tray 1021 alongside wall 1024 between a shipping position and an amplification detection position. At the position of delivering from the warehouse, thesample warehouse tray 1021 is located outside the PCR instrument, so that thesample 300 to be tested can be conveniently taken and put. In some embodiments, thesample 300 to be tested may be disposed in an experimental consumable such as a full skirt, a half skirt, no skirt, or eight consecutive rows of tubes, which is provided with a plurality of receiving cavities to receive thesample 300 to be tested. After thesample 300 to be tested is placed on thesample bin tray 1021, thesample bin tray 1021 may be moved to an amplification detection position, i.e., binning.

Fig. 6 illustrates an exemplary embodiment of atranslation drive assembly 1026 for moving thesample cartridge tray 1021. In some embodiments, thetranslational drive assembly 1026 may employ a rack and pinion mechanism, wherein therack 1027 may be fixed to thesample cartridge tray 1021, e.g., on a side wall of the bottom of thesample cartridge tray 1021. Gear 1028 is disposed on samplecompartment holding tray 1022 orfirst rack 1011 and is capable of meshing withrack 1027. The axis of the gear 1028 extends in the vertical direction V. This arrangement can simplify the structure and prevent the gear 1028 from jumping teeth on therack 1027, thereby improving stability.

Gear 1028 is driven bytranslation drive 1029. In some embodiments,translation drive 1029 may be a dc motor or a stepper motor. Of course, it should be understood that any other suitable drive mechanism is possible and is not strictly limited by this application. For example, in some alternative embodiments,translation drive 1029 may also employ a servo motor. Thetranslational drive portion 1029 includes an output shaft coupled to the gear 1028 for driving the rotation of the gear 1028. When the drive gear 1028 is rotated in one direction, the gear 1028 engages therack 1027 to drive thesample magazine tray 1021 from the amplification detection position, as shown in fig. 7, to the discharge position, as shown in fig. 6. When the drive gear 1028 is rotated in the opposite direction, the gear 1028 engages therack 1027 to drive the movement of thesample compartment tray 1021 from the out-bin position of fig. 6 to the amplification detection position shown in fig. 7. In the out-bin position, thesample bin tray 1021 is outside the PCR instrument so as to facilitate taking and placing of thesample 300 to be tested. At the amplification detection position, thesample bin tray 1021 is located inside the PCR instrument and aligned with theamplification unit 103 in the vertical direction V.

To facilitate smooth movement of thesample bin tray 1021, in some embodiments, the sample-receivingunit 102 can further comprise aguide strip 1020 and a guide slot. In some embodiments,guide strip 1020 may be disposed onbottom wall 1023 of samplecartridge retention disk 1022 and spaced a predetermined distance fromside wall 1024, as shown in fig. 8. The predetermined distance may be determined based on factors such as the structure and material of thesample bin tray 1021. The guide grooves are formed on thesample cartridge tray 1021, for example, at the bottom of thesample cartridge tray 1021. The guide strips 1020 are received in the guide slots and the guide slots slidably engage the guide strips 1020 on the samplecompartment holding tray 1022, thereby providing guidance for movement of thesample compartment tray 1021 to move from the amplification detection position shown in fig. 8 to the ejection position shown in fig. 9. In some embodiments, to facilitate the sliding fit of theguide strip 1020 and the guide groove, rounded protrusions, rollers, or a lubricant may be disposed on theguide strip 1020 therebetween.

In some embodiments, thesample holding unit 102 may further include astop strip 1030.Stop bar 1030 may be disposed onside wall 1024 of sample silo fixedtray 1022. Corresponding protrusions or step structures may be provided on the outer side wall of thesample compartment tray 1021 adjacent to theside wall 1024, such that theretention strip 1030 is capable of retaining at least a portion (e.g., the protrusion or step structure) of thesample compartment tray 1021 between theretention strip 1030 and thebottom wall 1023. On the one hand, thespacing bars 1030 can limit the position of thesample bin tray 1021 in the vertical direction V, thereby avoiding the risk of thesample bin tray 1021 tilting or tipping over. On the other hand, thespacing bars 1030 can also provide further guidance for the movement of thesample tray 1021, thereby making the movement of thesample tray 1021 more smooth.

To facilitate controlling thetranslation drive 1029 to stop driving at a suitable position to enable thesample cartridge tray 1021 to stop at the out-feed position or the amplification detection position, in some embodiments, thetranslation drive assembly 1026 may include a sensor assembly (hereinafter referred to as a second sensor assembly for ease of illustration). The second sensor assembly may be any suitable means for detecting the position of thesample cartridge tray 1021 relative to the sample cartridge fixeddisk 1022, including but not limited to: hall elements, stops, opto-electronic switches, infrared sensing elements, etc. How to control thetranslation drive section 1029 to stop driving according to information of the second sensor assembly is described below with a stopper as an example of the second sensor assembly.

As shown in fig. 10, the second sensor assembly can include afirst stop 1058 and asecond stop 1059 secured to samplecompartment holding tray 1022. In response to a command or signal from a user to operate the PCR instrument to eject thesample compartment tray 1021, thetranslation driver 1029 drives thesample compartment tray 1021 to move from the amplification detection position shown in fig. 10 to the ejection position after other required steps are completed (as will be described further below). When thesample compartment tray 1021 moves into position, it touches thefirst stop 1058 at the exit position of the samplecompartment holding tray 1022. The touchedfirst stopper 1058 sends a signal to indicate that thesample bin tray 1021 has reached the discharging position, and at this time, thetranslational driving unit 1029 is controlled to stop driving, so that thesample bin tray 1021 stops at the discharging position to take and place thesample 300 to be tested.

After thesample 300 is placed, thetranslation driving unit 1029 drives thesample bin tray 1021 to move from the delivery position to the amplification detection position in response to a command or signal from the user operating the PCR instrument to put thesample bin tray 1021 in the bin. When thesample compartment tray 1021 moves into position, it will touch thesecond stop 1059 located at the location of the rear wall of the samplecompartment holding tray 1022. The touchedsecond stopper 1059 sends a signal to indicate that thesample bin tray 1021 has reached the amplification detection position, and at this time, thetranslation driving unit 1029 is controlled to stop driving, so that thesample bin tray 1021 stops at the amplification detection position, so as to perform the temperature rise-temperature decrease cycle and qualitative and quantitative detection on thesample 300 to be detected.

Of course, it should be understood that the above-described embodiments employing a stop with respect to the second sensor assembly are merely illustrative and are not intended to limit the scope of the present application. Any other suitable means capable of sensing the position of thesample cartridge tray 1021 relative to the samplecartridge securing tray 1022 is possible. For example, as mentioned previously, in some embodiments, the second sensor assembly may also be a hall element, a photoelectric switch, an infrared sensing element, or the like. Further, in some embodiments, alternatively or additionally, a second sensor assembly may also be disposed on thesample bin tray 1021.

Thesample 300 to be measured on thesample bin tray 1021 reaching the amplification detection position after being put into the bin can be subjected to a temperature rise-temperature fall cycle for amplification. Because theamplification unit 103 needs to lean against and support the consumables holding thesample 300 to be detected when amplifying thesample 300 to be detected, in most of the conventional PCR instruments with detection functions, thesample bin tray 1021 can be taken out of the bin together with theamplification unit 103, which causes the problems of complicated in-and-out mechanism, difficult assembly, large occupied area and the like. Unlike the conventional PCR instrument with a detection function, theamplification unit 103 of theamplification apparatus 100 according to the embodiment of the present application can be movably disposed on thefirst support 1011 in the vertical direction V under the driving of the elevating drivingassembly 105. In this way, the independent discharging function of thesample bin tray 1021 in thesample accommodating unit 102 can be realized, thereby simplifying the discharging structure and thus reducing the assembling difficulty.

Fig. 11-13 illustrate an exemplary embodiment of thelift drive assembly 105. An exemplary structure of the elevatingdrive assembly 105 will be described below with reference to fig. 11 to 13. In some embodiments, thelift drive assembly 105 may include alift drive 1051 and a pair of drive link assemblies. In some embodiments,lift drive 1051 may employ a dc motor or a stepper motor similar totranslation drive 1029 mentioned previously. Of course, it should be understood that any other suitable drive mechanism is possible and is not strictly limited by this application. In some alternative embodiments, the elevating drivingpart 1051 may also adopt a servo motor. A pair of drive link assemblies may be provided at the front and rear ends of theamplification unit 103, respectively, as shown in fig. 11 to 13. It should be understood that "front" and "rear" are referred to herein with respect to the in-out position of thesample bin tray 1021. The side of thesample bin tray 1021 that enters and exits the bin is the "front" side (i.e., the inlet side mentioned above) and the side opposite the front side is the "back" side (i.e., the back wall side mentioned above). Set up transmission link assembly like this and can avoid transmission link assembly to lead to the fact the wind channel that is located the left and right sides to shelter from to further improve the cooling efficiency ofamplification unit 103 when cooling down the processing to thesample 300 that awaits measuring. It should be understood that in some embodiments, the drive linkage assembly may also be disposed on the left and right sides of theamplification unit 103.

Each drive link assembly includes adrive wheel 1052, afirst link 1055, asecond link 1056, and adrive link 1054, as shown in fig. 11-13. The twodrive wheels 1052 of a pair of drive link assemblies may be connected and rotate synchronously by a connecting rod that is concentric with the axis of the twodrive wheels 1052. The connecting rod may be provided with a gear that is rotatable with the connecting rod. Another gear engaged with the gear may be provided on the output shaft of theelevation driving part 1051. The gear ratio of the two gears cooperating with each other can be chosen appropriately so that the rotation speed of thedriving wheel 1052 and thus the lifting speed of theamplification unit 103 can be controlled better.

Thedriving wheel 1052 is eccentrically provided with apivot shaft 1053. One end of thetransmission lever 1054 is rotatably provided on thepivot shaft 1053, and the other end is rotatably provided together with a first end of thefirst link 1055 and a first end of thesecond link 1056. The second end of thefirst link 1055 is rotatably provided on thefirst bracket 1011. For example,first support 1011 also includes ariser 1012 located between the two uprights. The second end of thefirst link 1055 may be rotatably disposed on theriser 1012. The second end of thesecond link 1056 is rotatably provided on theamplification unit 103. In addition, at least one of the two drive link assemblies further includes achute mechanism 1057. Thechute mechanism 1057 is fixed to thefirst bracket 1011. For example, to the previously mentionedriser 1012. Thechute mechanism 1057 includes a chute arranged in the vertical direction V for the second end of thesecond link 1056 to slide therein.

In this way, under the driving of thelifting driving part 1051, thetransmission wheel 1052 rotates to drive thetransmission rod 1054 to swing. The swinging of thetransmission rod 1054 further drives the swinging of thefirst linkage 1055 and thesecond linkage 1056. The swinging of thesecond link 1056 causes the second end of thesecond link 1056 to move up and down along the slide of theslide mechanism 1057, thereby moving theamplification unit 103 up and down. Movement of theamplification unit 103 between the raised and lowered positions is thereby achieved with a simple and labor-saving drive linkage assembly. In the raised position, theamplification unit 103 pushes and supports thesample 300 to be measured disposed in thesample bin tray 1021 toward the opticalfiber fixing component 104, and performs temperature adjustment on thesample 300 to be measured, so that thesample 300 to be measured is amplified. In the lowered position, theamplification unit 103 is disengaged from thesample 300 to be tested, so that the unloading of thesample bin tray 1021 holding thesample 300 to be tested is not affected. In some embodiments, thechute mechanism 1057 can also be part of theupright plate 1012, and the chute can also be correspondingly formed in theupright plate 1012.

To facilitate controlling theelevation drive 1051 to stop driving at a suitable position to enable theamplification unit 103 to stop at a raised position or a lowered position, in some embodiments, theelevation drive assembly 105 may include a sensor assembly (hereinafter referred to as a first sensor assembly for ease of illustration). The first sensor assembly may be any suitable means for detecting the position ofamplification unit 103 relative to samplecompartment holding tray 1022, including but not limited to: hall elements, stops, opto-electronic switches, infrared sensing elements, etc. How to control the liftingdrive part 1051 to stop driving according to the information of the first sensor assembly is described below with a photoelectric switch and alight coupling flap 1049 as an example of the first sensor assembly.

As shown in fig. 12, thelight coupling flap 1049 in the first sensor assembly may be fixed to thedrive wheel 1052 and rotate with thedrive wheel 1052. The first sensor assembly may further include two opto-electronic switches, i.e., a first opto-electronic switch 1050 and a second opto-electronic switch 1060, respectively, disposed onriser 1012 offirst support 1011. The position of the opticalcoupling blocking piece 1049 is set such that when the drivingamplification unit 103 reaches the lifted position, the opticalcoupling blocking piece 1049 rotates to the position of the firstphotoelectric switch 1050 to trigger the first photoelectric switch 1050 (for example, by shielding), so that thelifting driving part 1051 stops driving; and when the drivingamplification unit 103 reaches the lowered position, the opticalcoupling blocking piece 1049 rotates to the position of the secondphotoelectric switch 1060 to trigger the secondphotoelectric switch 1060, so that thelifting driving part 1051 stops driving. That is, by providing the photoelectric switch and the photo-coupling flap 1049, the position of theamplification unit 103 relative to the sample compartment fixedtray 1022 can be indirectly detected.

In this way, in response to a command or signal from the user to operate the PCR instrument to eject thesample compartment tray 1021, theelevation driving section 1051 drives theamplification unit 103 to move from the elevated position to the lowered position, thereby detaching theamplification unit 103 from the sample accommodated in thesample compartment tray 1021. When the drivingamplification unit 103 reaches the lowered position, the opticalcoupling blocking piece 1049 rotates to the position of the secondphotoelectric switch 1060 to trigger the secondphotoelectric switch 1060, so that thelifting driving part 1051 stops driving. Thetranslation drive 1029 then drives thesample cartridge tray 1021 from the amplification detection position to the ejection position.

After thesample 300 is taken or placed, thetranslation driving unit 1029 drives thesample bin tray 1021 to move from the delivery position to the amplification detection position in response to a command or a signal from the user operating the PCR instrument to put thesample bin tray 1021 in the bin. After reaching the amplification detection position (thesecond stopper 1059 is touched), theelevation driving unit 1051 drives theamplification unit 103 to move from the lowered position to the raised position, so that theamplification unit 103 pushes and supports the sample contained in thesample chamber tray 1021 towards the opticalfiber fixing component 104, and performs temperature adjustment on thesample 300 to be detected to complete amplification and qualitative and quantitative detection.

Of course, it should be understood that the above-described embodiments in which the photoelectric switch and thelight coupling flap 1049 are employed with respect to the first sensor assembly are merely illustrative and are not intended to limit the scope of the present application. Any other suitable means capable of sensing the position ofamplification unit 103 relative to samplecompartment holding tray 1022 is possible. For example, as mentioned previously, in some embodiments, the first sensor assembly may also be a hall element, a photoelectric switch, an infrared sensing element, or the like. Furthermore, in some embodiments, alternatively or additionally, the first sensor assembly may also be disposed on theamplification unit 103 and/or any other suitable location.

Embodiments in accordance with the present application also provide a method for controlling in a PCR instrument. Fig. 14 shows a flow chart of the method. The method may be performed by a control unit of the PCR instrument to complete the in and out binning operation of thesample bin tray 1021. In response to acquiring a signal to de-magazine thesample magazine tray 1021, the control unit may cause theelevation drive 1051 to drive theamplification unit 103 via the drive link assembly from the raised position to the lowered position at block 610. The signal to bin thesample bin tray 1021 may be obtained by any suitable means, for example, by the user clicking on an associated indication on a screen (e.g., "bin out"), or clicking on a bin out button in a PCR instrument, or the like. Atblock 620, a first arrival signal of theamplification unit 103 reaching the lowered position is obtained from the first sensor assembly. Upon acquiring the first arrival signal, the control unit stops driving of theelevation driving unit 1051 and causes thetranslation driving unit 1029 to drive thesample bin tray 1021 to move from the amplification detection position to the ejection position inblock 630. Subsequently, atblock 640, a second arrival signal is obtained from the second sensor assembly that thesample bin tray 1021 reached the out-bin position. Upon acquiring the second arrival signal, atblock 650, thetranslation drive 1029 is caused to stop driving thesample cartridge tray 1021. In this way, thesample bin tray 1021 stops at the discharge position.

At this time, the user can take and place thesample 300 to be tested on thesample bin tray 1021. After thesample 300 is taken or placed, the control unit may cause thetranslation driving unit 1029 to drive thesample bin tray 1021 to move from the delivery position to the amplification detection position in response to acquiring a signal for delivering thesample bin tray 1021. Similarly, the signal to bin thesample bin tray 1021 may be obtained by any suitable means, for example, by the user clicking on an associated indication on a screen (e.g., "bin"), or clicking on a bin button in a PCR instrument, or the like. Then, the control unit acquires a third arrival signal of thesample cartridge tray 1021 arriving at the amplification detection position from the second sensor assembly. Upon acquiring the third arrival signal, the control unit causes thetranslation drive unit 1029 to stop driving thesample bin tray 1021, and causes theelevation drive unit 1051 to drive theamplification unit 103 to move from the lowered position to the raised position via the transmission link assembly. Subsequently, the control unit acquires a fourth arrival signal of theamplification unit 103 reaching the lifted position from the first sensor assembly. Upon acquiring the fourth arrival signal, the control unit stops driving theelevation driving unit 1051. In this way, theamplification unit 103 pushes and supports thesample 300 to be tested accommodated in thesample bin tray 1021 towards the opticalfiber fixing component 104, and performs temperature adjustment on thesample 300 to be tested to complete amplification and detection.

An exemplary embodiment of theamplification unit 103 according to an embodiment of the present application will be described below with reference to fig. 15 and 16. In some embodiments,amplification unit 103 can includetemperature control component 1031 andheat dissipation component 1033.Temperature control assembly 1031 may include a temperature control board,temperature control module 108, andheat transfer medium 1081. The temperature control plate adopts a closed hollow structure. A plurality ofreaction chambers 1032 are formed in the temperature control plate. The temperature control plate of the hollow structure may be made of a material having an excellent heat transfer coefficient. The material having an excellent heat transfer coefficient can promote uniform distribution of the temperature control plate. In addition, the inner wall of the temperature control plate can be provided with a loose capillary structure, so that the heat transfer effect is improved by increasing the heat contact area. The open capillary structure is a microstructure having a regular or irregular pattern with a micro size (e.g., a micron size), for example, the open capillary structure may include a microstructure groove or a microstructure pit or protrusion, etc., which are in the shape of a straight line, a curve, a polygon, a circle, an ellipse, etc. The loose capillary structure can increase the thermal contact area to improve the heat transfer effect on one hand, and can promote the backflow of the condensed liquid phase-change material (such as liquid water, acetone, liquid ammonia and the like) on the other hand. In some embodiments, the loose capillary structure may be achieved by spraying copper powder or the like during manufacture. In alternative embodiments, the loose capillary structure may also be achieved by sand blasting and machining.

The plurality ofreaction chambers 1032 of the temperature control plate are arranged to be capable of aligning with theopenings 1025 on thebottom wall 1023 of the samplecompartment fixing tray 1022 when thesample compartment tray 1021 is in the amplification detection position, so that the temperature control plate can respectively push and support the plurality ofsamples 300 to be tested accommodated in thesample compartment tray 1021 through the plurality ofreaction chambers 1032 through theopenings 1025 to perform temperature adjustment on thesamples 300 to be tested.

The temperature control plate of the hollow structure may have an opening so that a vacuum state can be drawn in the cavity of the temperature control plate through the opening, and the cavity may be filled with a phase-changeable medium (e.g., water).Temperature control module 108 is coupled to the temperature control plate by a thermally conductive medium 1081 to provide heating from the back side of the temperature control plate. The heat-conducting medium 1081 may have a good heat transfer coefficient, for example, the heat-conducting medium 1081 may include, but is not limited to: heat conductive gel, heat conductive carbon film, heat conductive silicone grease, etc.

Whentemperature control module 108 is heating, the heat transfer through heat conducting medium 1081 can effectively cause the phase-changeable medium in the cavity of the temperature control plate to be heated. Taking the phase-changeable medium as water for example, the water is heated and then converted into steam which rapidly rises to the top surface of the inner part of the temperature control plate, releases heat on the top surface of the inner wall of the temperature control plate and is condensed into liquid water which flows back to the lower part of the cavity of the temperature control plate along the loose capillary structure. That is, the capillary structure also has a function of refluxing the condensed liquid. The above heating process causes the upper wall of the temperature control plate to rapidly heat up, and also causes the inner wall of thereaction chamber 1032 to heat up at the same time. In the process that the phase-changeable medium is heated, the temperature in thereaction chamber 1032 rises, and meanwhile, the temperature is conducted to thesample 300 to be tested in the consumable, so that thesample 300 to be tested is heated to the denaturation temperature, and the DNA double-strand opening of thesample 300 to be tested is completed. Meanwhile, the water vapor is liquefied and reflows above the inner part of the cavity of the temperature control plate, so that the medium in the cavity of the temperature control plate can be recycled. When thetemperature control module 108 is cooled (to the renaturation temperature), thesample 300 to be tested is copied. Thetemperature control module 108 performs multiple heating-cooling cycles to copy thesample 300 to be tested.

In some embodiments, thetemperature control module 108 for controllably performing multiple temperature rise-and-fall cycles on thesample 300 to be tested can include one or morepeltier elements 1082. FIG. 16 shows aPeltier element 1082 as an example oftemperature control module 108, wherein a heat conducting medium 1081 is also shown, arranged above and belowtemperature control module 108. Thepeltier element 1082 is a plate-like member utilizing the peltier effect. Thepeltier element 1082 has two sides (i.e., a side adjacent to the temperature control board and a side adjacent to the heat sink 1033). When a direct current flows through the device, it carries heat from one side to the other, causing one side to become cold and the other to become hot. For example, during a temperature-increasing cycle, the side adjacent to the temperature-controlling plate may be heated. During the cool down cycle, a reverse current may be applied or not applied, causing one side adjacent theheat sink 1033 to become hot and the other side to become cold.

It should be understood that the above embodiments in which thetemperature control module 108 employs thepeltier element 1082 are merely illustrative and are not intended to limit the scope of the present application. Any other suitabletemperature control module 108 capable of performing multiple temperature ramp-down cycles on thesample 300 to be tested in a controlled manner is also possible. For example, in some embodiments, thetemperature control module 108 can also be heated by using resistance wires, ceramic heating, or microwaves. The inventive concept according to the present application will be described hereinafter primarily with reference topeltier elements 1082 as an example of thetemperature control module 108. The other cases are similar, and will not be described in detail below.

Meanwhile, a heat conductive medium 1081 is also disposed between thetemperature control module 108 and theheat dissipation assembly 1033. In this way, during the cooling cycle, the heat conducted by thetemperature control module 108 from the temperature control board and the consumables can be rapidly transferred to theheat sink 1033 and dissipated by theheat sink 1033 to achieve the purpose of rapid cooling.

Referring back to fig. 15, in some embodiments, theheat sink assembly 1033 includes a heat sink,heat sink fins 1035 and afan 1036 disposed on the heat sink. The heat radiating body is made of a heat conductive material. For example, in some embodiments, the heat spreader may be made of a material (e.g., copper) having a good thermal conductivity. In some embodiments, theheat sink fins 1035 may be integrally formed with the heat sink. In some alternative embodiments, theheat sink fins 1035 and the heat sink can also be manufactured separately and assembled together. Thefan 1036 is coupled to theheat dissipation fins 1035 directly or indirectly, and is capable of causing air to flow in a predetermined direction in theheat dissipation fins 1035 to dissipate heat from the heat sink. For example, in some embodiments,temperature control assembly 1031 also includes a heat sink duct, which may include a pair of mountingwalls 1071 and endwalls 1072. The mountingwall 1071 is provided at least on the outer side of theheat radiation fins 1035 in parallel with the extending direction of theheat radiation fins 1035. For example, in some embodiments, to facilitate connection, as shown in fig. 15, mountingwalls 1071 may be disposed outside both theheat sink fins 1035 and the heat sink. Theend walls 1072 join the pair of mountingwalls 1071 and are disposed at the ends of theheat sink fins 1035. In some embodiments, the pair of mountingwalls 1071 and endwalls 1072 of the heat dissipation duct may be integrally formed by stamping sheet metal or molding, or the like. In alternative embodiments, the stack of cooling ducts may be assembled by welding, bonding, or fastening a pair of mountingwalls 1071 and endwalls 1072.

An air inlet may be formed in theend wall 1072 as shown in fig. 15. Thefan 1036 can be coupled to theheat sink fins 1035 via the end wall 1072 (i.e., indirectly coupled to the heat sink fins 1035), and the air outlet of thefan 1036 is aligned with the air inlet of theend wall 1072. In this way, the air blown by thefan 1036 can enter from the air inlet, and after the air passes through theheat dissipation fins 1035 to remove heat, the air can flow out from the left air outlet port and the right air outlet port in the extending direction of theheat dissipation fins 1035. The effect of this design is that the cold air outside the temperature control device can enter from the bottom of theheat dissipation fins 1035 under the action of thefan 1036, and finally flows out of theheat dissipation fins 1035 from the left and right ends of the heat dissipation air duct after being in full contact with theheat dissipation fins 1035 inside the heat dissipation air duct. Therefore, the air flow channel is short and smooth, and the two air outlet ports of the heat dissipation air channel are arranged in a bilateral symmetry manner, so that the overall temperature of the heat dissipation body is uniformly distributed, and the heat dissipation efficiency of the heat dissipation body is improved.

As described above in conjunction with fig. 2 and 3, avent 1014 is provided on thebottom plate 1013 at a position corresponding to theamplification apparatus 100. Since the inlet of thefan 1036 is adjacent to thebottom plate 1013, thevents 1014 may be disposed at positions corresponding to thefan 1036 to facilitate the circulation of the air flow. For example, thevents 1014 may be aligned with the inlet locations of thefans 1036. In order to prevent foreign matters from entering the heat dissipation air duct, a screen plate or the like may be provided in thevent 1014. In some alternative embodiments, thevent 1014 may also include a plurality of small vents. In addition,heat sink fins 1035 may be disposed adjacent toheat sink 903, such that a flow of hot air fromheat sink fins 1035 may dissipate out of the PCR instrument throughheat sink 903.

In some embodiments,heat sink assembly 1033 further comprises at least oneheat pipe 1037 disposed in the heat sink adjacent the plurality ofreaction chambers 1032. Fig. 15 shows 8heat pipes 1037 arranged in parallel. Eachheat pipe 1037 is an independent closedcylindrical heat pipe 1037, and a cooling medium may be disposed therein. In order to facilitate the arrangement of theheat pipes 1037, heat pipe accommodating chambers corresponding in number to the number of theheat pipes 1037 may be provided in the heat radiating body. Prior to disposing theheat pipe 1037 in the corresponding heat pipe receiving cavity, in some embodiments, a thermally conductive medium may be disposed around theheat pipe 1037, thereby facilitating heat transfer between theheat pipe 1037 and the heat dissipation body. In some embodiments, theheat pipes 1037 may also be shrink-fitted into the corresponding heat pipe receiving cavities to achieve a tight fit of theheat pipes 1037 and the heat pipe receiving cavities to further facilitate heat transfer therebetween. In alternative embodiments, theheat pipe 1037 may also be asingle heat pipe 1037 having an S-configuration.

By arranging theheat pipe 1037 at one side of the heat dissipation body close to thetemperature control module 108, when thetemperature control module 108 performs cooling and heat dissipation, theheat pipe 1037 can quickly spread heat in the axial direction of the heat pipe 1037 (i.e., the extending direction of the heat pipe 1037), thereby avoiding heat accumulation and formation of temperature gradient of the heat dissipation body in the heat dissipation process, and improving the heat dissipation efficiency of the whole temperature control device.

In some embodiments, to couple and secure thetemperature control component 1031, and the control circuit board and the like to theheat sink assembly 1033, the temperature control device may further include apressing member 1034. Thecompression member 1034 is coupled to theheat sink assembly 1033 around at least a portion of thetemperature control assembly 1031, as shown in fig. 5 and 15. In some embodiments, thecompression component 1034 can be a component having a "mouth" shaped configuration with a hollow portion capable of protruding at least the plurality ofreaction chambers 1032 of the temperature control plate. Meanwhile, the pressingmember 1034 can press thetemperature control component 1031 toward theheat sink 1033, so that reliable thermal contact between thetemperature control component 1031 and theheat sink 1033 can be maintained to thereby improve thermal efficiency.

In some embodiments, thecompression member 1034 may be integrally formed by suitable manufacturing means, which may include bosses or the like that cooperate with a temperature control device. In some alternative embodiments, thecompression component 1034 may also include multiple separate components. For example, in some embodiments, the pressingmember 1034 may also include a plurality of elongated members or members having a right-angle bend, and the connection between thetemperature control assembly 1031 and theheat dissipation assembly 1033 is achieved by disposing these members along the edge of the temperature control board while being fixedly coupled to the heat dissipation body. In this manner, the manufacture and assembly of the hold-down component 1034 may be facilitated.

An exemplary embodiment of the lowerfiber securing assembly 104 will be described below in conjunction with FIG. 15. In some embodiments, thefiber fixation assembly 104 includes afiber fixation plate 1041. Thefiber fixing plate 1041 is for fixing the end of the guidingfiber 22 and includes a plurality of fiber fixing holes. Each of the fiber holding holes is for receiving and holding an end of one of the guidingfibers 22. The end of each guidingoptical fiber 22 is fixed in the corresponding optical fiber fixing hole, so that the plurality of guidingoptical fibers 22 can be prevented from being wound, and the assembly and maintenance of the PCR instrument are facilitated. The distal end of theguide fiber 22 may be secured in the fiber securing hole by any suitable means. For example, in some embodiments, each of the guidingfibers 22 has a protective sheath or shell at the distal end that can be snapped by a snap member into a predetermined configuration in the fiber securing hole to position and secure the distal end of the guidingfiber 22.

Of course, it should be understood that the manner in which the ends of theguide fibers 22 are secured as mentioned above is merely illustrative and is not intended to limit the scope of the present application. Any other suitable means are possible as long as the end of the guidingfiber 22 can be positioned or fixed. For example, in some alternative embodiments, the end of theguide fiber 22 may be positioned and secured in the fiber securing hole by interference fit, adhesive, fastener connection, etc., and no limitation is made herein on how the end of theguide fiber 22 is secured in the fiber securing hole.

In some embodiments, thefiber fixation assembly 104 includes athermostatic cover 1042 and athermal shield 1043 in addition to thefiber fixation plate 1041. Thethermostatic cover 1042 is disposed on a side of thefiber fixing plate 1041 adjacent to the consumable containing thesample 300 to be tested, and is configured to be heated to a predetermined temperature (e.g., about 100 ℃) to heat the consumable from the top thereof. The predetermined temperature may be set higher than the temperature within the consumable. In one aspect, heating from the top can facilitate temperature control and maintenance of thesample 300 to be tested. On the other hand, the high temperature of the top can prevent thesample 300 to be measured from condensing on the top or the side of the consumable to affect the reliability of the detection.

In some embodiments, thethermostatic cover 1042 can be electrically connected to a control component of the PCR instrument. The control means controls theconstant temperature cover 1042, for example, according to a temperature rise-fall cycle, so that theconstant temperature cover 1042 is heated as necessary. Thethermostatic cover 1042 may achieve heating by any suitable means. For example, in some embodiments, thethermostatic cover 1042 can achieve heating using resistive heating, ceramic heating, or peltier element heating, among others.

To facilitate transmission of the excitation light and the emission light conducted via theguide fiber 22, thethermostatic cover 1042 has a plurality of through holes. The through-holes are aligned with the positions of the optical fiber fixing holes in the vertical direction V, thereby avoiding the blocking of the excitation light and the emission light by theconstant temperature cover 1042.

An insulatingplate 1043 is fixed between thefiber fixing plate 1041 and theconstant temperature cap 1042 to achieve isolation of theconstant temperature cap 1042 at a high temperature from the end of the guidingfiber 22. Theheat shield 1043 has a plurality of mounting holes. Likewise, to avoid blocking of the excitation light and the emitted light, the mounting holes are aligned with the through holes and the fiber fixing holes in the vertical direction V.

A plurality oflenses 1044 are respectively fixed in corresponding mounting holes, onelens 1044 being fixedly disposed in each mounting hole. In some embodiments, thelens 1044 may be a convex lens with one side substantially planar and the other side convex in the axial direction. The end of the guidingfiber 22 is fixed at the focal position of thelens 1044. In this way, on the one hand, thelens 1044 can collimate the excitation light transmitted through theguide fiber 22 and emit the collimated excitation light to thesample 300 to be measured, so that the concentration of the excitation light can be increased and the loss can be avoided. On the other hand, thelens 1044 can also collimate the emitted light so that it can enter the guidingfiber 22 entirely to avoid detection errors due to scattering of the emitted light.

More importantly, alens 1044 is disposed between the end of the guideoptical fiber 22 and the heatingmember thermostatic cover 1042. Thelens 1044 itself has a high temperature resistant characteristic and is not damaged by the high temperature of thethermostatic cover 1042. Thelens 1044 can block the propagation of the high temperature of thethermostatic cover 1042 to the end of the guidingoptical fiber 22, thereby effectively avoiding the adverse effect of the high temperature on the guidingoptical fiber 22. For guidingfibers 22 made of plastic, thethermal shield 1043 and thelens 1044 disposed therein can avoid the problems of aging, even melting and damaging, of theplastic guiding fibers 22 due to the high temperature. In addition, thethermal shield 1043 and thelens 1044 disposed therein can block the influence of high temperature on the size of the assembly gap of the guidingoptical fiber 22 and the guidingoptical fiber 22 with the optical fiber fixing hole, regardless of whether the guidingoptical fiber 22 is made of plastic or the guidingoptical fiber 22 is made of glass, thereby avoiding the problem that the gap is increased due to high temperature to affect the detection accuracy and reliability.

In addition, by providing theheat insulation plate 1043, heat loss of theconstant temperature cap 1042 on a non-working surface (i.e., a surface in contact with the heat insulation plate 1043) can be reduced, so that heat emitted from theconstant temperature cap 1042 can be more efficiently conducted to the upper side of the container containing thesample 300 to be measured. In this way, the temperature control of thethermostatic cover 1042 can be more accurate, and the stability of the temperature field inside the PCR instrument can be further improved.

In some embodiments, thethermal shield 1043 may be made of phenolic. Phenolic plastic is called bakelite, and is a material with high mechanical strength, good insulation, heat resistance and corrosion resistance. Phenolic plastics are made by adding a filler to a phenolic resin. Different fillers are added into the phenolic resin to obtain the modified phenolic plastics with different functions. For example, asbestos, mica, and other fillers may be added to the phenolic resin to increase acid, alkali, and abrasion resistance. To increase the hardness, glass fibers may be added to the phenolic resin. In order to improve the oil resistance and impact resistance, nitrile rubber can be added. In order to improve mechanical strength and acid resistance, it may be modified with polyvinyl chloride. In order to improve various properties, thethermal insulation board 1043 according to the embodiment of the present application may use the above-mentioned phenolic plastics modified with various fillers.

Of course, it should be understood that the embodiment of thethermal shield 1043 made of phenolic plastic is merely illustrative and is not intended to limit the scope of the present application. It is also possible to make the insulatingboard 1043 of any other suitable material. For example, in some alternative embodiments, theinsulation panels 1043 may also be made of mold insulation panels. The mold insulation board is a high performance insulation board made of a composite material of glass fibers and any suitable resin (e.g., a high temperature resistant resin). The phenolic plastic or the mold thermal insulation board is selected to keep good mechanical strength in a high-temperature environment, and meanwhile, the thermal conductivity coefficient of the material is very small, so that the temperature of the installation position of the guideoptical fiber 22 can be kept within the normal use temperature range of the guideoptical fiber 22 for a long time.

In some embodiments, to further increase the compactness of the structure, thefiber fixation plate 1041 may have a recess on a side adjacent to the consumable. The recess may have theheat shield plate 1043 and theconstant temperature cap 1042 disposed therein. This can maintain the compactness while maintaining a certain thickness of theinsulation board 1043 having high insulation performance. In addition, the concave portion can further reduce the heat loss of thethermostatic cover 1042 on the non-working surface, thereby further improving the accuracy of temperature control of thethermostatic cover 1042.

Thefiber fixation plate 1041 and thethermal shield 1043 and thethermostatic cover 1042 may be secured together by any suitable means, including but not limited to: adhesive, snap fit, fastener connections, and the like. In some embodiments, thethermal shield 1043 and thethermostatic cover 1042 may also be fastened together in a recess of thefiber fixation plate 1041 by a common plurality of fasteners.

To facilitate mounting of thelens 1044, in some embodiments, an O-ring may be provided around the periphery of thelens 1044. On one hand, the O-ring can improve the sealing performance of thelens 1044 in the mounting hole of theheat insulation plate 1043, thereby further preventing the hot air flow generated by thethermostatic cover 1042 from affecting the guidingoptical fiber 22. On the other hand, an O-ring having some flexibility and elasticity may provide some cushioning, thereby facilitating consistent installation and securing of thelens 1044 to a predetermined location.

In some embodiments, the mounting hole may have a stop therein. A stop can axially stop the O-ring to prevent thelens 1044 and O-ring from moving toward the end of theguide fiber 22. Thereby ensuring the reliability of the mounting of thelens 1044. In some embodiments, the through-hole of thethermostatic cover 1042 may have a step at an end of the through-hole adjacent to theheat insulating plate 1043. The stepped portion may have a portion of thelens 1044 disposed therein. Under the combined action of the step part, the stopping part and the O-shaped ring, thelens 1044 can be stably fixed at a preset position in the axial direction and the radial direction, thereby improving the reliability of the whole PCR instrument.

After theamplification apparatus 100 is used to amplify the gene of thesample 300 to be detected in thesample holding unit 102, theoptical detection apparatus 200 may be used to perform fluorescence detection on thesample 300 to be detected in thesample holding unit 102. Next, an exemplary structure and operation principle of theoptical detection apparatus 200 will be described with reference to fig. 17 to 28.

Fig. 17 shows a schematic layout of anoptical detection apparatus 200 according to an embodiment of the present application. As shown in fig. 17, theoptical detection device 200 is disposed on thesecond carriage 800. Thesecond bracket 800 may include a plurality of columns vertically disposed on thebottom plate 1013. Thesecond bracket 800 may be disposed on thebase plate 1013 in any suitable manner including, but not limited to: threaded connections, i.e. each upright in thesecond bracket 800 is screwed directly into a corresponding hole in thebase plate 1013; connecting a fastener; welding; or interference fit, etc. Thepower supply unit 400 is disposed at the bottom of thesecond bracket 800.

Theoptical detection device 200 may include one or more detection channels (also referred to as fluorescence channels) for detecting one or more target genes of interest in thesample 300 to be tested contained in the sample-holdingunit 102 at the amplification detection position. If there are multiple target genes to be detected in onesample 300 to be detected, then multiple fluorescence channels are needed to work, and if only one target gene is to be detected, then only one fluorescence channel is needed to work.

Fig. 18 shows a schematic structural diagram of anoptical detection apparatus 200 according to an embodiment of the present application. As shown in fig. 18, theoptical inspection apparatus 200 described herein includes abase 21, a plurality of guideoptical fibers 22 as mentioned above, a drivingmember 23, aturntable 24, and a plurality ofoptical devices 25.

As shown in fig. 18, thebase 21 is substantially square with rounded corners. It should be understood that a square shape is an exemplary shape of thebase 21, and other shapes of the base 21 are possible, such as a circle, a rectangle, other polygons, and the like, and the embodiments of the present application are not limited thereto.

Thebase 21 has afirst side 211 and asecond side 212 opposite thefirst side 211. When theoptical detection device 200 is placed in the orientation shown in fig. 18, thefirst side 211 is a top side of thebase 21 and thesecond side 212 is a bottom side of thebase 21. It should be understood that thefirst side 211 and thesecond side 212 of the base 21 may be oriented in other directions when theoptical detection device 200 is placed in other orientations. Thebase 21 is provided with a set of throughholes 210, each throughhole 210 extending from afirst side 211 to asecond side 212 of thebase 21.

The guidingfiber 22 is arranged at afirst side 211 of thebase 21. One end (also referred to as a proximal end) of eachguide fiber 22 is disposed corresponding to one of the throughholes 210 of thebase 21. In one embodiment, the proximal end of each guidingfiber 22 may be aligned with a respective throughhole 210 and at a distance from thefirst side 211 of thebase 21. In another embodiment, the proximal end of eachguide fiber 22 may be aligned with a respective through-hole 210 and substantially flush with thefirst side 211 of thebase 21. In yet another embodiment, the proximal end of each guidingfiber 22 may extend from thefirst side 211 of the base 21 into the respective throughhole 210. It should be understood that these arrangements of the proximal end of theguide fiber 22 are possible and embodiments of the present application are not strictly limited in this regard.

As mentioned above, the other end (also referred to as a distal end) of each guidingfiber 22 is fixed in a corresponding fiber fixing hole of thefiber fixing plate 1041 so as to be adjacent to thecorresponding sample 300 to be measured. With this arrangement, eachguide fiber 22 can transmit excitation light generated by theoptical device 25 to thecorresponding sample 300 to be measured, and transmit emission light emitted from theexcited sample 300 to be measured back to theoptical device 25. It should be understood that the profile of the guidingfiber 22 at theoptical detection device 200 shown in fig. 3 and the profile of the guidingfiber 22 at theoptical detection device 200 shown in fig. 17 and 18 and later in fig. 26 and 27 are schematic, but two arrangements of the guidingfiber 22 are shown, and there is no substantial difference.

In one embodiment, the throughhole 210 in thebase 21 is divided into a first partial hole for disposing the guidingfiber 22 and a second partial hole for calibrating theoptical detection device 200. For example, as shown in fig. 18, 100 throughholes 210 are provided on thebase 21, wherein 96 throughholes 210 are used as a first partial hole for providing the corresponding guidingoptical fiber 22, and 4 throughholes 210 are not occupied by the guidingoptical fiber 22 and are used as a second partial hole for calibrating theoptical detection apparatus 200. In calibrating theoptical detection device 200, a fluorescent calibration piece may be placed into the second portion of the well not occupied by the guidingfiber 22, excitation light is irradiated into the fluorescent calibration piece using the optics to be calibrated 25, and emission light is received from the fluorescent calibration piece. It will be appreciated that in some cases, additional optical fibres may be provided at the second portion aperture, such fibres leading out to other locations on theoptical detection device 200, to facilitate the placement of the fluorescence calibration member at such locations. This arrangement facilitates replacement of the fluorescent calibration member.

It should be noted that the numbers, values, etc. mentioned above and possibly elsewhere in this application are exemplary and are not intended to limit the scope of this application in any way. Any other suitable numbers, values are possible.

Thedriver 23 may be supported by thebase 21 and include an output shaft (not shown). The output shaft of the drivingmember 23 extends from thesecond side 212 of thebase 21, and theturntable 24 is located on thesecond side 212 of thebase 21 and is sleeved on the output shaft. When thedriver 23 is operated, thedial 24 can rotate with the output shaft of thedriver 23.

In some embodiments, thedrive 23 may comprise a stepper motor. In other embodiments, thedrive member 23 may comprise other types of motors, and embodiments of the present application are not limited in this regard.

In theoptical detection apparatus 200, a plurality ofoptical devices 25 are provided on theturntable 24 in order to detect target genes of different kinds. Eachoptical device 25 can emit excitation light of a specific wavelength range and receive emission light of another specific wavelength range, thereby detecting a specific kind of target gene of interest. In one embodiment,carousel 24 may be provided with 8optics 25 for detecting 8 different target genes. Of course, more or feweroptical devices 25 may be disposed on theturntable 24, and the embodiments of the present application are not limited in this respect. In some cases, even only oneoptic 25 may be provided ondisk 24 if only one target gene of interest is to be detected. In the case where a plurality ofoptical devices 25 are provided, the respectiveoptical devices 25 may have similar outer structures, differing mainly in that the components contained inside may be different. An exemplary structure of theoptical device 25 will be described below with reference to fig. 19 to 24.

Fig. 19 shows a schematic structural diagram of anoptical device 25 according to an embodiment of the present application. Theoptical device 25 shown in fig. 19 is one example of the plurality ofoptical devices 25 shown in fig. 18. It should be understood that otheroptical devices 25 may have similar structures.

As shown in fig. 19, theoptical device 25 includes an excitation-light generating module 251, a transmission-light receiving module 252, and a Y-shapedoptical fiber 253. The excitationlight generation module 251 is used for generating excitation light, which is guided to thesample 300 to be tested, and excites the sample to generate emission light. The emissionlight receiving module 252 is configured to receive the emission light emitted from theexcited sample 300 to be tested, and convert the received light signal into an electrical signal, such as a current signal. The Y-shapedoptical fiber 253 is connected to both the excitationlight generation module 251 and the emissionlight reception module 252 for transmitting the excitation light and the emission light. Theoptical device 25 may further comprise asubstrate 254, thesubstrate 254 may provide mechanical support for the excitationlight generation module 251 and the emissionlight receiving module 252 on the one hand, and may provide electrical connections to the excitationlight generation module 251 and the emissionlight receiving module 252 on the other hand. In the case where the transmitting and receivingoptical module 252 converts the optical signal into the current signal, thesubstrate 254 may further convert the current signal into the voltage signal.

Next, an exemplary structure of the Y-shapedoptical fiber 253 will be described with reference to fig. 20 and 21. Fig. 20 illustrates a structural diagram of a Y-shapedoptical fiber 253 according to an embodiment of the present application, and fig. 21 illustrates a structural diagram of afirst end 2530 of the Y-shapedoptical fiber 253 according to an embodiment of the present application. As shown in fig. 20 and 21, Y-fiber 253 includes a centraloptical fiber 2531 and a plurality of circumferentialoptical fibers 2532. First ends 2530 ofcentral fiber 2531 andcircumferential fiber 2532 are bound together and thus may also be referred to as first ends 2530 of Y-shapedfibers 253. At afirst end 2530 of the Y-shapedoptical fiber 253, each circumferentialoptical fiber 2532 is arranged around a centraloptical fiber 2531. Atsecond end 2533 of each circumferentialoptical fiber 2532, circumferentialoptical fibers 2532 are bound together.Second end 2533 of centraloptical fiber 2531 andsecond end 2533 of circumferentialoptical fiber 2532 are spaced apart from each other. Thesecond end 2533 of the centraloptical fiber 2531 is for connection to the excitationlight generating module 251, while thesecond end 2533 of the circumferentialoptical fiber 2532 is for connection to the emissionlight receiving module 252, as will be further described below in connection with fig. 23 and 24.

Referring to fig. 18 to 21, thefirst end 2530 of the Y-shapedoptical fiber 253 is disposed on thesecond side 212 of the base 21 corresponding to the throughhole 210 of thebase 21. With rotation of theturntable 24, thefirst end 2530 of the Y-shapedoptical fiber 253 can be sequentially aligned with each through-hole 210 in thebase 21. When the first ends 2530 of the Y-shapedoptical fibers 253 are aligned with the respective throughholes 210, the excitation light generated by the excitationlight generation module 251 can be irradiated to thecorresponding sample 300 to be measured via the centraloptical fiber 2531, the corresponding throughholes 210 aligned with the first ends 2530 of the Y-shapedoptical fibers 253, and the corresponding guideoptical fibers 22 disposed corresponding to the corresponding throughholes 210, so as to excite the sample and generate the emission light. The emissionlight receiving module 252 may receive the emission light emitted from the illuminatedsample 300 to be measured via the corresponding guidingoptical fiber 22, the corresponding throughhole 210, and the circumferentialoptical fiber 2532. In this way, theoptical device 25 can realize continuous fluorescence detection of a plurality ofsamples 300 to be detected, which can improve the fluorescence detection efficiency of the PCR instrument on one hand and improve the fluorescence detection precision of the PCR instrument on the other hand.

In some embodiments, unlike the embodiment shown in fig. 19, thesecond end 2533 of the centraloptical fiber 2531 may be connected to the emissionlight receiving module 252, and thesecond end 2533 of the circumferentialoptical fiber 2532 may be connected to the excitationlight generating module 251. In this case, the excitation light generated by the excitationlight generation module 251 may be irradiated to thecorresponding sample 300 to be measured via the circumferentialoptical fiber 2532, the corresponding throughhole 210 aligned with thefirst end 2530 of the Y-shapedoptical fiber 253, and the corresponding guideoptical fiber 22 disposed corresponding to the corresponding throughhole 210, so as to excite the sample to generate emission light; the emissionlight receiving module 252 can receive the emission light emitted from the illuminatedsample 300 to be measured via the corresponding guidingfiber 22, the corresponding throughhole 210, and thecentral fiber 2531.

An exemplary use of theoptical detection apparatus 200 is described below with reference to detecting a target substrate. For example, to detect the target genes of 96samples 300, theoptical device 25 for detecting the target genes is aligned with one guidingfiber 22 to complete the detection of one sample, and then theturntable 24 is rotated to align theoptical device 25 with the next guidingfiber 22 to complete the detection of thesecond sample 300. After theturntable 24 rotates one circle, the detection of 96samples 300 to be detected can be completed.

In some embodiments, instead of arranging a plurality of circumferentialoptical fibers 2532 aroundfirst end 2530 of centraloptical fiber 2531, a single circumferentialoptical fiber 2532 may be arranged around onlyfirst end 2530 of centraloptical fiber 2531. The emissionlight receiving module 252 can also receive emission light emitted from the irradiatedsample 300 to be measured by using the single circumferentialoptical fiber 2532.

FIG. 22 shows the relative arrangement with thefirst end 2530 of the Y-shapedoptical fiber 253 aligned with the guideoptical fiber 22 according to one embodiment of the present application. As shown in fig. 22, thecentral fiber 2531 has a diameter a, thefirst end 2530 of the Y-fiber 253 has a diameter b, theguide fiber 22 has a diameter c, theguide fiber 22 is spaced apart from thefirst end 2530 of the Y-fiber 253 by a distance d, thecentral fiber 2531 has a divergence angle α, and theguide fiber 22 has a divergence angle β. The diameter of each optical fiber described herein refers to the clear diameter of each optical fiber and does not include the size of the opaque structures at the periphery of each optical fiber.

In some embodiments, diameter a, diameter b, and diameter c satisfy a first relationship: b > c > a. Since the diameter c of theguide fiber 22 is larger than the diameter a of thecentral fiber 2531, the excitation light emitted from thecentral fiber 2531 can be received more by theguide fiber 22. Further, since the diameter b of thefirst end 2530 of the Y-shapedoptical fiber 253 is larger than the diameter c of the guideoptical fiber 22, the emitted light emitted from the guideoptical fiber 22 can be received more by the circumferentialoptical fiber 2532. In this way, the fluorescence detection accuracy of the PCR instrument can be further improved.

In some embodiments, the divergence angle α, the divergence angle β, the separation d and the diameter a, the diameter b, the diameter c satisfy a second relationship:

，

。

it has been found by calculation and experiments that, in the case where the second relationship is satisfied, the excitation light emitted from the centraloptical fiber 2531 can be substantially entirely irradiated into the guideoptical fiber 22, and the emission light emitted from the guideoptical fiber 22 can be substantially entirely irradiated into thefirst end 2530 of the Y-shapedoptical fiber 253. With such an arrangement, the PCR instrument can achieve excellent fluorescence detection accuracy.

It should be understood that the guidingfiber 22 shown in fig. 22 is one example of the plurality of guidingfibers 22 shown in fig. 18, and that other guidingfibers 22 may also satisfy the first and second relationships described above.

Next, an exemplary structure of the excitationlight generation module 251 will be described with reference to fig. 23. In some embodiments, as shown in fig. 23, the excitationlight generation module 251 includes afirst housing 2510, alight source 2511, a first convex lens 2512, a secondconvex lens 2513, anexcitation light filter 2514, and a thirdconvex lens 2515. Alight source 2511, a first convex lens 2512, a secondconvex lens 2513, anexcitation light filter 2514, and a thirdconvex lens 2515 are sequentially provided in thefirst case 2510. Thelight source 2511 emits excitation light when energized. Thelight source 2511 may be a laser, a halogen lamp, a xenon lamp, a high/low pressure mercury lamp, a Light Emitting Diode (LED), etc., and embodiments of the present application are not limited thereto. The first convex lens 2512 is configured to condense excitation light emitted by thelight source 2511. The secondconvex lens 2513 is configured to condense light from the first convex lens 2512 into parallel light, and pass to theexcitation light filter 2514. Theexcitation light filter 2514 is configured to filter the received parallel light to obtain light of a desired specific wavelength, and pass the filtered parallel light to the thirdconvex lens 2515. The thirdconvex lens 2515 is used for converging the filtered parallel light to thesecond end 2533 of the centraloptical fiber 2531, and emitting the filtered parallel light into the centraloptical fiber 2531 as excitation light. With this arrangement, it is possible to reliably generate excitation light and irradiate the excitation light into the centeroptical fiber 2531. Subsequently, the centraloptical fiber 2531 can transmit excitation light to the guideoptical fiber 22 aligned with thefirst end 2530 of the centraloptical fiber 2531, thereby illuminating thecorresponding sample 300 to be measured.

In an embodiment according to the present application, the excitationlight generation module 251 may include more convex lenses or filters, and such excitationlight generation module 251 may also generate excitation light and irradiate the excitation light into the centraloptical fiber 2531. In some embodiments, the excitationlight generation module 251 may further include other types of components, which is not limited in this embodiment of the present application.

Next, an exemplary structure of the transmission-light receiving module 252 will be described with reference to fig. 24. In some embodiments, as shown in fig. 24, the emissionlight receiving module 252 includes asecond housing 2520, afluorescence signal receiver 2521, a fourthconvex lens 2522, anemission light filter 2523, a fifthconvex lens 2524, and a sixthconvex lens 2525. Afluorescent signal receiver 2521, a fourthconvex lens 2522, anemission light filter 2523, a fifthconvex lens 2524, and a sixthconvex lens 2525 are sequentially disposed in thesecond housing 2520. A sixthconvex lens 2525 is proximate to thesecond end 2533 of the circumferentialoptical fiber 2532 to receive the emitted light from thesecond end 2533 of the circumferentialoptical fiber 2532 and to focus the emitted light. The fifthconvex lens 2524 is for converging light from the sixthconvex lens 2525 into parallel light, and transmitting the parallel light to theemission light filter 2523. Theemission light filter 2523 serves to filter the received parallel light, and transmits the filtered parallel light to the fourthconvex lens 2522. The fourthconvex lens 2522 is configured to condense the filtered parallel light to thefluorescent signal receiver 2521. Thefluorescent signal receiver 2521 is used to convert the received optical signal into an electrical signal, such as an electrical current signal. With this arrangement, it is possible to reliably receive the emitted light from the second ends 2533 of the circumferentialoptical fibers 2532 and convert the emitted light into electrical signals.

In embodiments according to the present application, the emissionlight receiving module 252 may include more convex lenses or filters, and such emissionlight receiving module 252 may also receive the emission light from thesecond end 2533 of the circumferentialoptical fiber 2532 and convert the emission light into an electrical signal. In some embodiments, thelight receiving module 252 may also include other types of components, which are not limited in this embodiment.

The optical path history of the detection process of the sample 300 to be detected is described in detail below with reference to fig. 18 to 24: first, the light source 2511 emits a beam of excitation light; the first convex lens 2512 condenses excitation light emitted from the light source 2511; the second convex lens 2513 condenses light from the first convex lens 2512 into parallel light; the excitation light filter 2514 filters the received parallel light; the third convex lens 2515 converges the filtered parallel light to the second end 2533 of the central optical fiber 2531, and emits the filtered parallel light into the central optical fiber 2531 as excitation light; the central optical fiber 2531 transmits the excitation light to the guide optical fiber 22 aligned with the first end 2530 of the central optical fiber 2531, so as to irradiate the corresponding sample 300 to be tested, and the sample 300 to be tested is excited to emit the emission light; the emitted light shines through the guide fiber 22 to the first end 2530 of the circumferential fiber 2532; a sixth convex lens 2525 receives the emitted light from the second end 2533 of the circumferential optical fiber 2532 and converges the emitted light; the fifth convex lens 2524 condenses light from the sixth convex lens 2525 into parallel light; the emission optical filter 2523 filters the received parallel light; the fourth convex lens 2522 converges the filtered parallel light to the fluorescent signal receiver 2521, completing the collection of the fluorescent signal, i.e. completing the detection of a sample 300 to be detected.

Returning to FIG. 18, to prevent the cables from twisting together during rotation of theturntable 24, theoptical detection device 200 also includes aconductive slip ring 27. An electricallyconductive slip ring 27 is provided on theturntable 24 for providing an electrical connection between thepower supply 400 and thecontrol circuit board 29 for powering theoptics 25.

FIG. 25 shows a schematic structural diagram of aconductive slip ring 27 according to one embodiment of the present application. As shown in fig. 25, theconductive slip ring 27 includes afixed end 272 and arotating end 271. Thefixed end 272 is provided with a fixedcable 274, and therotating end 271 is provided with arotating cable 273. Therotating end 271 is connected to theturntable 24, and therotating cables 273 are connected to the respectiveoptical devices 25. With this arrangement, theoptical device 25 can be reliably powered.

With continued reference to fig. 18, theoptical detection device 200 may also include acontrol circuit board 29, and thecontrol circuit board 29 may be used to implement some of the control functions of theoptical detection device 200.

In some embodiments, theoptical detection device 200 further comprises adust brush ring 28, as shown in FIG. 26. Adust brush collar 28 is disposed around the plurality ofoptics 25. In order to better show the specific structure of the dust-proof brush ring 28, the dust-proof brush ring 28 in fig. 26 is not located at an actual position, and the dust-proof brush ring 28 is actually fixedly connected with thebase 21. Through setting updustproof brush circle 28, can prevent dust and light-resistant, it is specific, whencarousel 24drives optics 25 and rotates,dustproof brush circle 28 is in relative quiescent condition, rotates the in-process throughoptics 25 anddustproof brush circle 28 frictional contact, can get rid of the dust or other pollutants that probably exist on theoptics 25.

In some embodiments, to monitor the rotational position ofdisk 24,optical detection device 200 further includes aposition sensor 26, as shown in fig. 27 and 28. Aposition sensor 26 is provided on theturntable 24. Accordingly, asense chip 261 may be provided on thebase 21. Asturntable 24 rotates,position sensor 26 will rotate withturntable 24. Ifposition sensor 26 is rotated to the position wheresensing chip 261 is located,position sensor 26 will generate a sensing signal indicating thatturntable 24 is rotated to a predetermined position. At this time, the drivingmember 23 may be controlled so that theturntable 24 stops rotating at a predetermined position. Subsequently, it can be observed whether theoptical device 25 is aligned with the throughhole 210 on thebase 21. If misaligned, theoptical detection device 200 may be adjusted to align theoptical device 25 with the through-hole 210 in thebase 21. In the embodiment of the present application, theposition sensor 26 may be an element having a positioning function, such as an optoelectronic switch, a hall switch, a mechanical travel switch, and a magnetic attraction element, which is not limited in this embodiment of the present application.

After theoptical detection device 200 is used to perform fluorescence detection on the plurality ofsamples 300 to be detected in thesample accommodating unit 102, thesample accommodating unit 102 may be moved from the amplification detection position to the delivery position by the aforementioned in-out operation method, so as to replace thesamples 300 to be detected in thesample accommodating unit 102. Subsequently, thesample holding unit 102 can be moved from the shipping position to the amplification detection position for the next cycle of gene amplification and fluorescence detection.

Having described embodiments of the present application, the foregoing description is intended to be exemplary, not exhaustive, and not limited to the disclosed embodiments. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The terminology used herein is chosen in order to best explain the principles of the embodiments, the practical application, or improvements made to the technology in the marketplace, or to enable others of ordinary skill in the art to understand the embodiments disclosed herein.

Claims (17)

1. A PCR instrument, characterized in that the PCR instrument comprises an amplification device (100) and an optical detection device (200),

the amplification apparatus (100) comprises:

a sample holding unit (102) comprising a sample bin tray (1021) for holding a plurality of samples (300) to be tested, the sample bin tray (1021) being adapted to move between a discharge position and an amplification detection position;

an amplification unit (103) movable in a vertical direction between a raised position, in which the amplification unit (103) is adapted to perform temperature regulation of the plurality of samples to be tested (300), and a lowered position, in which the amplification unit (103) is detached from the plurality of samples to be tested (300); and

a fiber fixing assembly (104) disposed on the top of the sample accommodating unit (102) and including a fiber fixing plate (1041), the fiber fixing plate (1041) being provided with a plurality of fiber fixing holes aligned in the vertical direction with the plurality of samples (300) to be measured,

the optical detection device (200) comprises:

a base (21) provided with a set of through holes (210);

a plurality of guiding optical fibers (22), one end of each guiding optical fiber being disposed corresponding to one through hole of the set of through holes (210) at the first side (211) of the base (21), the other end of each guiding optical fiber being fixed in a corresponding optical fiber fixing hole on the optical fiber fixing plate (1041);

the rotary table (24) is positioned on the second side (212) of the base (21) and sleeved on the output shaft of the driving piece (23); and

at least one optical device (25) arranged on the carousel (24), each optical device (25) comprising an excitation light generation module (251), a transmission light reception module (252) and a Y-shaped optical fiber (253), the Y-shaped optical fiber (253) comprising a central optical fiber (2531) and at least one circumferential optical fiber (2532), a first end (2530) of the central optical fiber (2531) and the at least one circumferential optical fiber (2532) being constrained together and adapted to be aligned successively with each through hole of the set of through holes (210) upon rotation of the carousel (24), a second end (2533) of the central optical fiber (2531) being connected to one of the excitation light generation module (251) and the transmission light reception module (252), a second end (2533) of the at least one circumferential optical fiber (2532) being connected to the other one of the excitation light generation module (251) and the transmission light reception module (252), the excitation light generation module (251) is configured to generate excitation light and irradiate the excitation light to a corresponding sample (300) to be tested via the Y-shaped optical fiber (253), a corresponding through hole of the set of through holes (210) aligned with the first end (2530) of the Y-shaped optical fiber (253), and a corresponding guide optical fiber of the plurality of guide optical fibers (22) disposed corresponding to the corresponding through hole, and the emission light receiving module (252) is configured to receive emission light emitted from the irradiated sample (300) to be tested via the corresponding guide optical fiber of the plurality of guide optical fibers (22), the corresponding through hole of the set of through holes (210), and the Y-shaped optical fiber (253).

2. The PCR machine according to claim 1, wherein the amplification device (100) further comprises a first bracket (1011), and the sample receiving unit (102) and the amplification unit (103) are movably disposed on the first bracket (1011), respectively.

3. The PCR instrument according to claim 2, wherein the amplification device (100) further comprises an elevation drive assembly (105), the elevation drive assembly (105) being coupled to the amplification unit (103) and comprising an elevation drive section (1051) and a pair of transmission linkage assemblies, the elevation drive section (1051) driving the amplification unit (103) to move between the raised position and the lowered position via the pair of transmission linkage assemblies, each transmission linkage assembly of the pair of transmission linkage assemblies comprising:

a transmission wheel (1052) coupled to the elevation driving part (1051) to be driven to rotate by the elevation driving part (1051), and including an eccentrically disposed pivot shaft (1053);

a first link (1055) including a first end and a second end rotatably disposed on the first bracket (1011);

a transmission rod (1054) rotatably connected between the pivot shaft (1053) and the first end of the first link (1055);

a second link (1056) including a first end and a second end, the first end of the second link (1056) rotatably connected to the first end of the first link (1055), the second end of the second link (1056) rotatably connected to the amplification unit (103); and

a chute mechanism (1057) fixedly disposed on the first bracket (1011) and including a chute disposed in the vertical direction for the second end of the second link (1056) to slide therein.

4. The PCR instrument according to claim 3, wherein the sample receiving unit (102) further comprises:

a sample compartment holding tray (1022) fixedly disposed on the first rack (1011) and comprising a bottom wall (1023) and a pair of side walls (1024), the bottom wall (1023) comprising an opening (1025); and

a translation drive assembly (1026) coupled to the sample bin tray (1021) to drive movement of the sample bin tray (1021) along the sidewall (1024).

5. The PCR machine of claim 4 wherein the translation drive assembly (1026) comprises:

a rack (1027) disposed on the sample bin tray (1021) and moving with the sample bin tray (1021);

a gear (1028) disposed on the first bracket (1011) or the sample compartment fixed disk (1022) and engaged with the rack (1027), and an axis of the gear (1028) extending in the vertical direction; and

a translation drive (1029) including an output shaft coupled to the gear (1028) to drive the gear (1028) in rotation.

6. The PCR instrument of claim 4, wherein the sample receiving unit (102) further comprises:

a guide strip (1020) disposed on the bottom wall (1023) of the sample cartridge fixed disk (1022) spaced a predetermined distance from the side wall (1024); and

a guide slot formed on the sample compartment tray (1021) and adapted for the guide strip (1020) to be slidably disposed therein to provide a guide for movement of the sample compartment tray (1021).

7. The PCR machine of claim 6, wherein the sample receiving unit (102) further comprises:

a retention strip (1030) formed on the side wall (1024) spaced a predetermined distance from the bottom wall (1023), the retention strip (1030) being adapted to retain at least a portion of the sample bin tray (1021) between the retention strip (1030) and the bottom wall (1023).

8. The PCR instrument of claim 4, wherein the elevation drive assembly (105) further comprises:

a first sensor assembly coupled to at least one of the sample compartment holding tray (1022) and the amplification unit (103) and adapted to detect a position of the amplification unit (103) relative to the sample compartment holding tray (1022).

9. The PCR machine of claim 4 wherein the translational drive assembly (1026) further comprises:

a second sensor assembly coupled to at least one of the sample compartment fixed disk (1022) and the sample compartment tray (1021), and adapted to detect a position of the sample compartment tray (1021) relative to the sample compartment fixed disk (1022).

10. The PCR machine according to claim 4, wherein the amplification unit (103) comprises:

a temperature control assembly (1031) comprising a plurality of reaction chambers (1032) and arranged to align with the opening (1025) when the sample compartment tray (1021) is in the amplification detection position such that the amplification unit (103) supports the sample (300) to be tested when in the raised position and temperature conditions the sample (300) to be tested in a controlled manner; and

a heat dissipation assembly (1033) thermally coupled to the temperature control assembly (1031) and comprising a heat dissipation body, heat dissipation fins (1035) disposed on the heat dissipation body, and a fan (1036), the fan (1036) being coupled to the heat dissipation fins (1035) and adapted to flow air in a predetermined direction among the heat dissipation fins (1035) to dissipate heat from the heat dissipation body.

11. The PCR instrument of claim 10, wherein the temperature control assembly (1031) further comprises a heat dissipation air duct, the heat dissipation air duct comprising:

a pair of mounting walls (1071) provided at least on the outer side of the heat dissipation fins (1035) in parallel with the extending direction of the heat dissipation fins (1035); and

an end wall (1072) connecting the pair of mounting walls (1071) and disposed at an end of the heat dissipating fin (1035), the end wall (1072) having an air intake,

wherein the fan (1036) is coupled to the end wall (1072) and aligned with the air inlet such that the air enters from the air inlet and exits from two air outlet ports of the extension direction of the heat dissipating fins (1035) in the extension direction of the heat dissipating fins (1035).

12. The PCR instrument of claim 10, wherein the heat sink assembly (1033) further comprises:

at least one heat pipe (1037) disposed in the heat sink adjacent to the plurality of reaction chambers (1032).

13. The PCR instrument of any one of claims 1-12, wherein the fiber securing assembly (104) further comprises:

a thermostatic cover (1042) arranged on a side of the fiber fixation plate (1041) adjacent to the sample (300) to be measured and having a plurality of through holes aligned with the plurality of fiber fixation holes in the vertical direction;

an insulation plate (1043) fixed to the fiber fixing plate (1041) and located between the fiber fixing plate (1041) and the constant temperature cover (1042), the insulation plate (1043) having a plurality of mounting holes aligned with the plurality of fiber fixing holes in the vertical direction; and

a plurality of lenses (1044), each secured in a corresponding one of the mounting holes and located between the other end of the guiding fiber (22) and the thermostatic cover (1042), at least for collimating the excitation light and the emission light.

14. The PCR instrument according to any of the claims 1 to 12, wherein the second end (2533) of the central optical fiber (2531) is connected to the excitation light generation module (251), the second end (2533) of the at least one circumferential optical fiber (2532) is connected to the emission light receiving module (252), the central optical fiber (2531) has a diameter a, the first end (2530) of the Y-shaped optical fiber (253) has a diameter b, each of the plurality of guide optical fibers (22) has a diameter c, wherein the diameter a, the diameter b and the diameter c satisfy the following relation: b > c > a.

15. The PCR instrument of claim 14, wherein the central fiber (2531) has a divergence angle a, each of the plurality of guide fibers (22) has a divergence angle β, each of the plurality of guide fibers (22) has a spacing d in alignment with the first end (2530) of the Y-fiber (253), wherein the divergence angle a, the divergence angle β, the spacing d and the diameter a, the diameter b, the diameter c satisfy the following relationship:

，

。

16. the PCR instrument of any of claims 1-12 and 15, wherein the excitation light generation module (251) comprises a light source (2511), a first convex lens (2512), a second convex lens (2513), an excitation light filter (2514), and a third convex lens (2515), the light source (2511) is configured to emit excitation light, the first convex lens (2512) is configured to converge excitation light emitted by the light source (2511), the second convex lens (2513) is configured to converge light from the first convex lens (2512) into parallel light, the excitation light filter (2514) is configured to filter the parallel light, and the third convex lens (2515) is configured to converge the filtered parallel light to the second end (2533) of the central fiber (2531).

17. The PCR instrument according to any of the claims 1-12 and 15, wherein the emission light receiving module (252) comprises a fluorescence signal receiver (2521), a fourth convex lens (2522), an emission light filter (2523), a fifth convex lens (2524) and a sixth convex lens (2525), the sixth convex lens (2525) is configured to receive the emission light from the second end (2533) of the at least one circumferential optical fiber (2532) and to concentrate the emission light, the fifth convex lens (2524) is configured to concentrate the light from the sixth convex lens (2525) into parallel light, the emission light filter (2523) is configured to filter the parallel light, and the fourth convex lens (2522) is configured to concentrate the filtered parallel light to the fluorescence signal receiver (2521).

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