WO2019075695A1 - 自动分析装置及其样本分析方法 - Google Patents

自动分析装置及其样本分析方法 Download PDF

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Publication number
WO2019075695A1
WO2019075695A1 PCT/CN2017/106884 CN2017106884W WO2019075695A1 WO 2019075695 A1 WO2019075695 A1 WO 2019075695A1 CN 2017106884 W CN2017106884 W CN 2017106884W WO 2019075695 A1 WO2019075695 A1 WO 2019075695A1
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Prior art keywords
reaction vessel
unit
reaction
incubation
reagent
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PCT/CN2017/106884
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English (en)
French (fr)
Inventor
张震
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深圳迎凯生物科技有限公司
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Priority to PCT/CN2017/106884 priority Critical patent/WO2019075695A1/zh
Publication of WO2019075695A1 publication Critical patent/WO2019075695A1/zh

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations

Definitions

  • the automatic immunoassay analyzer usually consists of a sampling unit, a reaction unit, a supply and waste waste unit, a system control unit, and the like.
  • Luminescence immunity has become the mainstream technology of automatic immunity due to its advantages of quantitative detection, high sensitivity, good specificity, wide linear range and high degree of automation.
  • the fully automatic luminescence immunoassay differs according to the labeling method and the luminescence system, and includes enzymatic chemiluminescence, direct chemiluminescence, and electrochemiluminescence.
  • the reagents and analysis items are “one-one” correspondence, that is, the specific reagents corresponding to different analysis items are generally different in terms of formula, reagent amount, and component quantity.
  • the reagent typically includes multiple components, such as the usual 2-5 components, including reagent components such as magnetic particle reagents, enzyme labeling reagents, diluents, and the like.
  • reagent components such as magnetic particle reagents, enzyme labeling reagents, diluents, and the like.
  • multiple reagent components of an analysis item can be filled in one time or in multiple steps. When the step is added, the first reagent, the second reagent, and the third reagent are defined according to the order of filling. Wait.
  • Signal reagent for The generation of the measurement signal is usually one of the general-purpose reagents, and the analysis item is a "one-to-many" correspondence, that is, different analysis items share the signal reagent.
  • the incubation of the present invention specifically refers to the process of antigen-antibody binding reaction or biotin-avidin binding reaction of the reactants in the constant temperature environment of the incubation unit before the reaction container starts to be washed and separated, specifically, one-step incubation, To enter an incubation prior to wash separation, a one-step incubation is performed twice, including the first incubation before the second reagent is added and the second reagent is added after the second reagent is added, followed by a two-step incubation.
  • One-step method Refer to Figure 1, add sample (S) and reagent (R), mix (some test methods can also do not need to mix, the same below, no longer repeat), incubate (generally 5-60 Minutes), after the incubation is completed, wash and separate, add signal reagent, signal incubation (usually 1-6 minutes), and finally measure. It should be pointed out that due to the specific composition of the signal reagents, some luminescence systems do not require signal incubation, and can be directly measured during the process of filling the signal reagent or after filling the signal reagent.
  • the signal reagent may be one or more. Referring to Figure 2, the signal reagent includes a first signal reagent and a second signal reagent.
  • Two-step method The difference from the one-step method is that there is one more cleaning and separation step, and the other steps are the same.
  • a second prior art solution arranges the incubation and measurement together to form an incubation measurement unit, which is performed by another separate unit, although the technical solution reduces one measurement disc compared to the first prior scheme. To a certain extent, it is advantageous to control the size and cost of the whole machine, but there are also the same problems as the first technical solution.
  • the incubation measurement unit In order to achieve flexible incubation time, the incubation measurement unit is complicated to control, and the incubation and measurement are also controlled by each other. There are not only shortcomings such as high-speed automated testing, but also flexible signal incubation.
  • a third prior art solution achieves incubation, wash separation and measurement on a single-turn disc or a trajectory track.
  • the disc In order to support longer incubation times, the disc needs to be set in addition to cleaning separation and measurement positions. Many incubation positions, so in order to achieve high-speed testing, the size of the disc or the shape of the disc needs to be designed to be large, and the manufacturing process is difficult. The cost is high.
  • at least two loading mechanisms and at least two cleaning separation devices are required, thereby increasing material, processing, production cost and overall size.
  • this technical solution also limits the incubation time, resulting in problems such as a fixed incubation time and an excessively long time.
  • this technical solution is not only difficult to achieve the darkroom environment required for measurement, it requires an additional shutter mechanism, and flexible signal incubation is not possible.
  • the incubation unit of the present invention realizes the incubation of the reactants in the reaction vessel, and the separation of the reactants in the reaction vessel and the measurement of the signal in the reaction vessel are performed independently of the processing unit of the incubation unit, and the reaction vessel is between the incubation unit and the processing unit.
  • the transfer is achieved by the transfer unit.
  • the cleaning separation and measurement of the invention are respectively realized on the inner and outer rings on the processing disk, which not only eliminates the separate cleaning separation disk and the measuring disk, but also improves the reliability of the transfer of the reaction container, thereby simplifying the system structure and the control flow, Significantly reduced incubation unit and processing unit size and flexible incubation times with separate incubation units.
  • the invention improves the working efficiency of the analysis device, and solves the technical problems of large volume, low detection speed, high cost and poor performance of the current automatic instrument, which not only saves the laboratory space, improves the test efficiency, but also helps reduce the cost. Expenditure ultimately saves a lot of natural and social resources.
  • Figure 2 is a schematic diagram of a one-step reaction mode (another signal measurement mode);
  • Figure 4 is a schematic view showing a first embodiment of the automatic analyzer of the present invention.
  • Figure 7 is a two-step test flow chart
  • Figure 8 is a schematic view showing a second embodiment of the automatic analyzing device of the present invention.
  • the transfer of the reaction vessel between different locations in the apparatus of the invention can be accomplished by the transfer unit.
  • the transfer unit can be any suitable mechanism for transferring or moving the reaction vessel.
  • the preferred transfer unit of the present invention primarily comprises a drive mechanism, a horizontal motion robot arm, a pick and place mechanism, and the like.
  • the pick and place mechanism is usually a mechanical finger, which can hold the reaction container.
  • the horizontal motion mechanical arm can be driven along the X direction, the Y direction, the X direction and the Y direction, the radial direction, the circumferential direction, the radial direction and the circumferential direction by the driving mechanism.
  • the transfer unit can also move up and down, placing the reaction vessels in different positions or taking them out from different locations.
  • one or more transfer units can be set.
  • the invention may also include a filling station.
  • the filling station is located within the range of motion of the transfer unit and the filling unit or can be moved by horizontal motion to the range of motion of the transfer unit and the filling unit.
  • the filling station receives and carries the reaction vessel transferred from the transfer unit, and accepts the filling unit to fill the reaction container with the sample and the reagent.
  • a reaction vessel is placed on the filling station for placing a reaction vessel to which the sample and reagents need to be filled.
  • the mixing mechanism can be integrated in the filling station to ultrasonically mix, deflect or rotate the reaction vessel after each filling.
  • the mixture can be mixed by shaking, and the mixing mechanism, such as the ultrasonic generator, can be integrated into the filling unit, and the ultrasonic waves generated by the filling unit can be mixed at the same time as the sample and the reagent are added or after the filling operation is completed.
  • the filling station may not integrate the mixing mechanism, and the mixing may be performed by the suction and discharge action or the impact force of the filling unit.
  • the filling station can also be integrated on the incubation unit as a whole, so that the filling station can be located not under the trajectory of the transfer unit.
  • the processing unit cleans the reactants in the separation reaction vessel and measures the reaction signals in the reaction vessel.
  • the processing unit mainly comprises an insulation device, a treatment tray, a cleaning separation device and a measuring device.
  • the heat preservation device of the processing unit is similar to the incubation unit, and the periphery usually has insulation materials such as insulation cotton, and usually wraps or surrounds the bottom, the periphery and the upper portion of the treatment tray, the side or the bottom.
  • the inside of the part can be provided with a heating device and a sensor, and the upper part is generally a structure such as a cover plate, and provides a constant temperature incubation environment for the processing unit.
  • the heating device can also be mounted on the rotating device.
  • the processing disk comprises a driving, a transmission mechanism and an associated control circuit, etc., and controls and drives the processing disk to rotate at a fixed angle every fixed time (such as a cycle or a cycle), and the reaction container position transferred thereto advances a certain number.
  • Position (such as advancing a reaction vessel position). At least two reaction vessels on the spin disk are positioned within the range of motion of the transfer unit such that the transfer unit can move the reaction vessel into and out of the process tray.
  • the processing unit may also perform cleaning and separation of the reaction vessel on the separation and separation reaction vessel to remove unbound components in the reactant.
  • the cleaning and separating device of the processing unit of the present invention includes a magnetic field generating device and a flushing mechanism.
  • the magnetic field generating device provides a magnetic field environment for adsorbing paramagnetic particles in the reaction vessel to the inner wall of the reaction vessel.
  • the rinsing mechanism includes a liquid absorbing and injecting device that sucks unbound components in the reaction vessel and injects a washing buffer into the reaction after suction.
  • the liquid absorption device comprises a liquid suction part suitable for pumping liquid, such as a liquid suction needle, a liquid suction tube or a liquid suction nozzle, and the liquid absorption part is arranged above the processing unit, and can drive the reaction container in and out of the reaction container through the driving mechanism.
  • the unbound components in the reaction vessel are aspirated.
  • the cleaning separation device starts cleaning and separating the reaction container.
  • the cleaning and separating device may further couple the signal reagent filling mechanism, and after the cleaning and separation of the reaction container, all or part of the signal reagent is added thereto, for example, all the first and second signal reagents are added. Wait for or only add the first signal reagent, etc., and the remaining signal reagents can be added during the measurement. This makes full use of the function of the cleaning and separating device, which reduces the size of the mechanism and saves costs.
  • the measuring device can be connected or mounted to the heat insulating device of the processing unit in a general manner, such as directly mounted on the heat insulating device or mounted on the heat insulating device through an optical fiber connection, so that the measuring device can directly handle the processing.
  • the disk measures the signal in the reaction vessel at the reaction vessel position to avoid setting an independent measurement position or measuring disk, which makes the whole mechanism more compact, lower cost, simpler and more efficient control process, higher processing efficiency and higher reliability.
  • the processing unit of the present invention may further comprise a signal reagent filling mechanism for filling the reaction vessel in the reaction vessel position of the processing tray with a signal reagent.
  • the processing unit of the invention is independent of the incubation unit, which not only facilitates cleaning separation and measurement, but also realizes flexible incubation time, and solves the disadvantages of the prior art that the size of the whole machine is too large, the structure is complicated, and the incubation time is fixed.
  • the reagent storage unit refrigerates the reagent and transfers the target reagent to the aspirating reagent position.
  • the reagent storage unit usually adopts two methods: a reagent tray and a reagent cartridge.
  • the reagent tray In order to ensure the stability of the reagent, the reagent tray generally has a cooling function, such as 4 to 10 °C.
  • a plurality of reagent container positions are generally set on the reagent tray for placing the reagent container.
  • Each reagent container is provided with a plurality of independent chambers for storing different reagent components, such as magnetic particle reagents, enzyme labeling reagents, diluents and the like.
  • the automatic analysis device 100 includes a sample delivery unit 30, a reagent storage unit 40, a filling unit 20, a reaction container supply unit 70, a transfer unit 50, a processing unit 10, an incubation unit 80, a filling station 90, and the like. The functions and functions of each part are described below.
  • the sample delivery unit 30 is used to place the sample tube 31 to be inspected and deliver the target sample tube to the sample site.
  • the sample transport unit 30 is a sample tray on which a curved sample holder (not shown) is placed, and each of the curved sample holders is placed with 10 sample tubes 31.
  • the sample tray can be driven by the driving mechanism to transfer the target sample to the suction sample position under the control of the control center, and the suction sample position is located at the intersection of the horizontal motion track of the filling unit 20 and the center circle of the sample tube.
  • the reagent tray can be driven by the driving mechanism to transfer the target reagent bottle to the suction reagent position under the control of the control center.
  • the suction reagent position is located at the intersection of the horizontal movement track of the filling unit and the center circle of the reagent chamber.
  • the corresponding 4 Corresponding to the reagent components, there are 4 aspirating reagent sites (not shown).
  • the filling unit 20 completes the filling of the sample and the reagent.
  • the horizontal movement trajectory of the filling unit 20 intersects the sample position on the sample tray 30, the reagent position on the reagent disk 40, and the reaction container position on the filling station 90, respectively, and the intersection point is the suction sample position, the suction reagent position, and the addition.
  • the filling unit is a single sample loading mechanism, which can perform up and down and horizontal rotation movements, and both the sample and the reagent are added, so that the structure of the whole machine is more compact and the cost is lower.
  • the mixing unit 20 can also be integrated with a mixing mechanism such as an ultrasonic generator to ultrasonically mix the reaction container after each filling. In other embodiments, the mixing mechanism may be disposed on the filling station 90 for ultrasonically mixing or shaking the mixed reaction vessel.
  • the reaction vessel supply unit 70 stores and supplies a reaction vessel.
  • the reaction container supply unit adopts a pre-arranged type.
  • the reaction vessel supply unit 70 includes two reaction vessel trays on which a number of reaction vessel positions are disposed to store unused reaction vessels.
  • the reaction vessel supply unit 70 is within the horizontal range of motion of the transfer unit 50 such that the transfer unit 50 can traverse the unused reaction vessels at each reaction vessel location on the tray to provide an unused reaction vessel for the newly initiated test.
  • the transfer unit 50 can be moved horizontally to transfer the reaction vessel between different positions of the automated analysis device 100.
  • the transfer unit 50 is set to one, and the three-dimensional movement can be performed, which makes the whole machine more compact and lower in cost.
  • the transfer unit 50 includes an X-direction moving robot arm 50b, a Y-direction guide rail 50a, a Y-direction moving robot arm 50c, and a vertical motion mechanism and a mechanical finger (not shown).
  • the transfer unit 50 can simultaneously move the mechanical finger horizontally along the X direction and the Y direction, and the horizontal movement range covers the range within the boundary polygon 56, and the reaction of the reaction container on the reaction container supply unit 70, the filling station 90, and the incubation unit 80 can be performed.
  • the container position, the cleaning separation reaction container position 11a on the processing unit 10, the measurement reaction container position 11b, and the lost reaction container hole 60 are transferred.
  • the processing unit 10 separates the reactants in the reaction vessel from the incubation unit and measures the signal in the reaction vessel.
  • the heat preservation device of the processing unit 10 is a pot body 12 and an upper cover (not shown), the processing disk is 11, the cleaning and separating device is 16, and the measuring device is 86.
  • a heater and a sensor are arranged on the side or the bottom of the pot body 12, surrounding the bottom and the periphery of the processing tray 11, providing a constant temperature environment and a darkroom environment for the processing unit 10, preventing or reducing the loss of heat of the incubator unit 10 and the influence of external stray light.
  • the pot 12 also supports and secures the magnetic field generating means of the cleaning separator 16 to provide a magnetic field environment for cleaning separation.
  • the magnet generating device of the cleaning and separating device 16 is a permanent magnet device, which can provide a stronger and more stable magnetic field environment.
  • the rinsing mechanism of the cleaning separation device 16 includes a liquid absorbing device and a liquid injection device, and a mixing mechanism.
  • the cleaning and separating device 16 can also be coupled with a signal reagent filling mechanism to fill all or part of the signal reagent into the reaction vessel that has completed the cleaning separation.
  • the measuring device 86 includes a weak photodetector photomultiplier tube (PMT) that is directly mounted on the pot body 82 to measure the weak chemiluminescence signal generated after the signal reagent is added to the reaction vessel.
  • the processing tray 11 is rotatable about a central axis on which two reaction vessel positions 11a and 11b centered on the center of rotation are disposed.
  • the reaction vessel position on the inner ring 11a is the position of the cleaning separation reaction vessel
  • the reaction vessel position on the outer ring 11b is the measurement reaction vessel position, which not only facilitates the installation of the cleaning separation device and the measuring device, but also reduces the overall processing unit. size.
  • Step 200 loads the reaction vessel: the transfer unit 50 transfers an unused reaction vessel from the reaction vessel supply unit 70 to the reaction vessel location of the filling station 90,
  • Step 201 filling the sample and the reagent: the filling unit 20 respectively sucks the sampling sample and the reagent from the suction sample position and the suction reagent position into the reaction container on the reaction container position of the filling station 90,
  • Step 202 Mixing: If mixing is required, the mixing mechanism integrated in the filling station 4 mixes the sample and reagents in the reaction vessel. If you do not need to mix, omit this step,
  • Step 203 The transfer unit 50 transfers the reaction container filled with the sample and the reagent from the filling station to the reaction container position of one of the three rounds of the incubation tray 81 (81a, 81b, 81c), and the reaction container starts at the incubation unit. Incubate.
  • the incubation time of the reaction vessel in the incubation unit 81 varies depending on the specific test item, and is generally 5 to 60 minutes.
  • Step 204 Washing and separating: After the reaction vessel is incubated or incubated for a certain period of time, the transfer unit 50 transfers it from the reaction vessel position of the incubation unit 80 to the cleaning separation reaction vessel position on the inner ring 11a of the processing tray 11, and the processing tray 11 is fixed every time. The time is rotated forward by one position, and the reaction container on the separation reaction vessel is transferred to the cleaning and separating device 16, and the magnetic field of the cleaning and separating device 16 is passed through, and the washing mechanism and the mixing mechanism of the cleaning and separating device 16 complete the liquid absorption of the reaction container. Note to wash the buffer, wash and mix until the cleaning separation is completed.
  • Step 206 Signal Incubation: If signal incubation is desired, all or part of the signal incubation is completed while the processing tray 11 is transferred to the reaction vessel at the measuring reaction vessel position on the outer ring 11b to the measuring device 86. If no signal incubation is required, this step is omitted.
  • Step 207 When the reaction container to be measured is transferred to the measuring device 86, the reaction signal in the reaction container is measured by the measuring device 86, and the measurement result is processed and transmitted to the control center of the automatic analyzing device.
  • Step 208 discards the reaction vessel: transfer unit 50 transfers the measured reaction vessel from the measured reaction vessel location on outer ring 11b of processing tray 11 to the disposal vessel vessel 60 for disposal.
  • Step 302 Mixing: If mixing is required, the sampler integrated in the filling station 90 is sampled and in the reaction vessel. A reagent is mixed. If you do not need to mix, omit this step,
  • Step 303 The transfer unit 50 transfers the reaction container filled with the sample and the first reagent from the filling station 4 to the reaction container position of one of the three cycles (81a, 81b, 81c) of the incubation tray 81, and the reaction container starts. Incubate in the incubation unit.
  • the incubation time of the reaction vessel in the incubation unit 81 varies depending on the specific test item, and is generally 5 to 60 minutes.
  • Step 304 The second reagent is added: after the first incubation is completed, the transfer unit 50 transfers the reaction container from the reaction container position of the incubation unit 80 to the filling station 4 again, and the filling unit 20 draws the second reagent from the suction reagent position. Noted in the reaction vessel on the filling station 90,
  • Step 305 Mixing: If mixing is required, the mixer integrated in the filling station 90 mixes the sample in the reaction vessel with the first reagent. If you do not need to mix, omit this step,
  • step 404 is added to add a wash separation
  • Step 404 Washing separation: After the reaction vessel is incubated or incubated for a certain period of time, the transfer unit 50 transfers it from the reaction vessel position of the incubation unit 80 to the cleaning separation reaction vessel position on the inner ring 11a of the processing tray 11, and the processing tray 11 is fixed every time. The time is rotated forward by one position, and the reaction container on the separation reaction vessel is transferred to the cleaning and separating device 16, and the magnetic field of the cleaning and separating device 16 is passed through, and the washing mechanism and the mixing mechanism of the cleaning and separating device 16 complete the liquid absorption of the reaction container. The washing buffer is washed, washed and mixed until the washing separation is completed.
  • the transfer unit 50 transfers the reaction vessel from the washing and separating reaction vessel position on the inner ring 11a of the processing tray 11 to the filling station 90.
  • the filling unit 20 draws the second reagent from the suction reagent position into the reaction container on the filling station 90,
  • the automatic analysis device 100 adopts independent incubation units and processing units, and the incubation unit is not affected by the processing unit, which can realize flexible incubation time, and the processing unit simultaneously realizes cleaning separation and measurement, which not only saves the existing
  • the technology uses separate cleaning separation discs and measuring discs, which reduces the size of the machine and reduces the cost. It also streamlines the test procedure and reduces the complexity and difficulty of the control, avoiding the transfer of the reaction vessel between multiple discs.
  • the processing unit is disposed on the inner side of the processing unit by setting different reaction container positions
  • the measuring device is disposed outside the processing unit
  • the cleaning separation is performed in the cleaning separation reaction container position of the inner circumference of the processing tray, and the measurement is performed on the processing tray.
  • the measurement of the reaction vessel position of the outer ring not only eliminates the mutual influence of cleaning separation and measurement, but also reduces the size of the processing unit, making the structure of the whole machine more compact, lower in cost and higher in test efficiency.
  • the automatic analysis device of the present invention can be flexibly expanded and maximized to achieve serialization of products.
  • the number of transfer units and filling units can be increased, the size of the incubation unit can be appropriately increased, or the incubation can be increased.
  • the number of units is used to achieve this.
  • 8 is a second embodiment of the automatic analysis device of the present invention A schematic diagram of an embodiment.
  • the sample transport unit 30 adopts the injection mode of the track and the sample rack, so that more samples can be accommodated, the sample can be added in real time, and the operation is more convenient.
  • the first filling unit 21 is loaded with a disposable nozzle (Tip head), and 93 and 96 in FIG. 8 are a Tip head loading position and a Tip head unloading position, respectively.
  • the reaction vessel supply unit 70 can also provide a new Tip head.
  • the transfer unit 50 includes a first transfer unit 51 and a second transfer unit 52 that can perform three-dimensional movement independently.
  • the first transfer unit 51 is mainly in the reaction container supply unit 70, the incubation unit 80, the Tip head loading position, and the Tip head unloading position, and the reaction.
  • At least one wash separation reaction vessel location on the processing tray 11 and at least one measurement reaction vessel location are within the range of motion of the second transfer unit 52 such that the second transfer unit 52 can be between the incubation unit, the mixing station, the processing unit, and The reaction vessel is transferred between the separation reaction vessel position and the measurement reaction vessel position.
  • test procedure and steps of the present embodiment are mainly different from the first embodiment in that the filling sample and the reagent are completed by the first and second filling units; the filling of the sample and the reagent Both are completed in the reaction vessel position of the incubation unit; the mixing of the reaction vessel after the addition of the sample or reagent is completed by a separate mixing station; the reaction vessel transfer is coordinated by the first and second transfer units, other actions and processes The same or similar to the first embodiment, with reference to FIG. 5 to FIG. 7, will not be described again.
  • this embodiment avoids the extra large size of the cleaning separation disc and the measuring disc, and at the same time, the distribution of the processing unit itself is reduced by the distribution of the functionally different reaction container positions, thereby making the whole machine more Compact, lower cost, more efficient and more reliable.
  • the embodiment of the invention further provides a sample analysis method, which specifically includes:
  • Filling step filling the reaction vessel with samples and reagents
  • Incubating step incubating the reaction vessel on the reaction vessel site of the incubation unit
  • the reaction vessel is transferred between the incubation unit and the treatment unit and the cleaning separation reaction vessel of the treatment unit and the measurement reaction vessel of the treatment unit by a transfer unit.
  • the invention realizes the incubation of the reactants in the reaction vessel centering on the incubation unit, and washes and separates the reactants in the reaction vessel at the position of the cleaning and separation reaction vessel independently of the processing unit of the incubation unit and the reaction vessel on the measurement reaction vessel position.
  • the internal signal is measured, the transfer of the reaction vessel between the incubation unit and the processing unit, and the transfer between the different reaction vessel locations of the processing unit is achieved by the movement of the transfer unit.
  • the invention not only improves the reliability of the transfer of the reaction container, but also eliminates the separate cleaning and separation discs, reduces the system structure and the control flow, and can also significantly reduce the size of the processing unit, so that the incubation unit can realize flexible incubation time.
  • the invention improves the working efficiency of the analysis device, and solves the technical problems of large volume, low detection speed, high cost and poor performance of the current automatic instrument, which not only saves the laboratory space, improves the test efficiency, but also helps reduce the cost. Expenditure, reducing the burden on the subjects, ultimately saving a lot of natural and social resources.
  • Various embodiments may be included in various embodiments of the invention, which may be embodied as machine-executable instructions that are executable by a general purpose or special purpose computer (or other electronic device). Alternatively, these steps may be performed by hardware elements comprising specific logic circuitry to perform the steps or jointly by hardware, software and/or firmware.

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Abstract

一种自动分析装置(100)及样本分析方法，自动分析装置(100)包括：加注单元(20)，加注样本或/和试剂到反应容器；孵育单元(80)，孵育反应容器内的反应物；处理单元(10)，清洗分离反应容器内的反应物并测量反应容器内的反应信号；转移单元(50)，在不同位置之间转移反应容器。自动分析装置(100)以孵育单元(80)为中心实现反应容器内反应物的孵育，独立于孵育单元(80)的处理单元(10)为中心实现反应容器内反应物的清洗分离和反应容器内信号的测量，不仅省去了单独清洗分离盘和测量盘，精简了系统结构和控制流程，还可以显著缩减处理单元(10)和孵育单元(80)尺寸，并实现灵活的孵育时间。

Description

自动分析装置及其样本分析方法 技术领域
本发明涉及体外诊断设备领域，具体涉及一种自动分析装置及其样本分析方法。
背景技术
近年来，临床检验和自动化技术的发展和进步，不仅提升了临床实验室自动化水平，提高了医学检验的效率，也改善了检验结果的质量和可靠性。然而，随着检测标本量的增多，临床实验室需要不断增添大型自动化检测系统以满足其检测需求，从而导致实验室日益拥挤和检测成本不断攀升。因而，如何在面临日益增长的成本压力下，提升检验效率、保证结果并充分利用现有实验室资源，是临床检验要解决的一个迫切问题。
为了表述方便，本文以体外诊断(In-Vitro Diagnostics，简称IVD)中的全自动免疫分析仪，特别地，以发光免疫分析仪为列，阐述本技术方案和方法，本领域内技术人员应该理解，本发明方案和方法也可用于其它临床检验自动化装置，比如荧光免疫装置、电化学免疫等。全自动免疫分析通过以抗原抗体相互结合的免疫学反应为基础，使用酶标记、镧系元素标记或化学发光剂标记抗原抗体，通过一系列级联放大反应，将光信号或电信号与分析物浓度等相联系，分析人体样本中的待测的抗原或抗体，主要应用于医院的检验科、第三方独立实验室、血检中心等机构，对人类体液中的各分析物进行定量、半定量或定性检测，进行传染病、肿瘤、内分泌功能、心血管疾病和优生优育以及自身免疫类疾病等的诊断。全自动免疫分析仪通常由取样单元、反应单元、供应和废物废液单元、系统控制单元等组成。发光免疫由于具有定量检测、灵敏度高、特异性好、线性范围宽、自动化程度高等优势正成为目前自动化免疫的主流技术。全自动发光免疫分析根据标记方法和发光体系不同，又包括酶促化学发光、直接化学发光、电化学发光等。
参考附图1-3，发光免疫分析按测试原理和模式一般可分为一步法、延时一步法、两步法等，主要测试步骤一般包括加注样本和试剂、反应物混匀、孵育、清洗分离(Bound-Free，简称B/F)、加信号试剂、测量等。需要指出的是，为了表述方便，本发明区分了试剂和信号试剂、孵育和信号孵育。试剂与分析项目为“一一”对应关系，即不同分析项目对应的具体试剂在配方、试剂量、组分数量等方面一般不同。根据具体分析项目的不同，试剂通常包括多个组分，如常见的2-5个组分，包括磁微粒试剂、酶标试剂、稀释液等试剂组分。根据反应模式不同，一个分析项目的多个试剂组分可以一次性加注也可以分多个步骤加注，分步骤加注时按照加注次序定义为第一试剂、第二试剂、第三试剂等。信号试剂用于 测量信号的产生，通常为通用试剂的一种，与分析项目为“一对多”的对应关系，即不同的分析项目共用信号试剂。本发明的孵育特指反应容器开始清洗分离前，其内的反应物在孵育单元的恒温环境下发生的抗原抗体结合反应或生物素亲和素结合反应的过程，具体地，一步法孵育一次，为进入清洗分离前的一次孵育，延时一步法孵育两次，包括加注第二试剂前的第一次孵育和加注第二试剂后进入清洗分离前的第二次孵育，两步法孵育两次，包括第一次清洗分离前的第一次孵育和第二次清洗分离前的第二次孵育。而信号孵育指清洗分离后的反应容器在加入信号试剂后，在恒温环境下反应一段时间，使信号增强的过程。根据反应体系和发光原理的不同，并不是所有测试都需要信号孵育，需要信号孵育的测试一般为酶促类化学发光免疫分析。不同测试模式对应的测试步骤详述如下：
1)一步法：参考附图1，加注样本(S)和试剂(R)，混匀(有些测试方法也可以不需要混匀，下同，不再赘述)，孵育(一般为5-60分钟)，孵育完成后进行清洗分离,加注信号试剂，信号孵育(一般为1-6分钟)，最后测量。需要指出的是，由于信号试剂具体成分的不同，有些发光体系不需要信号孵育，在加注信号试剂过程中或加注完信号试剂后可以直接测量。信号试剂可以是一种或多种，参考附图2，信号试剂包括第一信号试剂、第二信号试剂。
2)延时一步法：与一步法不同之处在于试剂分两次加注，加第一试剂混匀后进行第一次孵育，第一次孵育完成后加第二试剂并混匀。与一步法相比多了一次孵育、加注试剂和混匀动作，其余流程与一步法一样。
3)两步法：与延时一步法不同在于多了一次清洗分离步骤，其它步骤相同。
为了实现上述流程自动化测试，现有的具体实现技术方案如下：
第一种现有技术方案将孵育、清洗分离和测量分开独立布局，分别由三个旋转圆盘完成相应功能，反应容器在不同单元之间由机械抓臂完成转移。该技术方案组件和单元多，反应容器需要在各单元之间转移，造成体积大、成本高、控制流程复杂等问题。
第二种现有技术方案将孵育和测量布置在一起构成孵育测量单元，清洗分离由另一个独立单元完成，虽然与第一种现有方案相比，该技术方案减少了一个测量圆盘，在一定程度上有利于控制整机尺寸和成本，但同样存在与第一种技术方案相同的问题。该技术方案为了实现灵活的孵育时间，孵育测量单元控制复杂，孵育和测量在控制上也会相互制约，不仅存在无法实现高速自动化测试等缺点，也无法实现灵活的信号孵育。
第三种现有技术方案将孵育、清洗分离和测量在一个单圈圆盘或歧形轨道上实现，该方案为了支持较长的孵育时间，圆盘除了清洗分离和测量位置外，还需要设置很多的孵育位置，这样为了实现高速测试，圆盘或歧形轨道尺寸需要设计得很大，生产制造难度大、 成本高，此外，为了实现延时一步法和两步法测试，还需要至少两个加样机构和至少两个清洗分离装置，从而增加了物料、加工、生产成本和整机尺寸。另一方面，该技术方案还限制了孵育时间，导致了孵育时间固定、出结果时间过长等问题。此外，该技术方案不仅很难实现测量所需的暗室环境，需要增加额外的快门机构，还无法实现灵活的信号孵育。
发明内容
为解决现有技术普遍存在的缺点和问题，本发明提供一种生产制造成本低、结构简单紧凑、测试流程或方法灵活高效的自动分析装置及其样本分析方法。
根据本发明的一方面，提供一种自动分析装置，包括：加注单元，加注样本或/和试剂到反应容器；孵育单元，孵育反应容器内的反应物；处理单元，清洗分离反应容器内的反应物并测量反应容器内的反应信号；转移单元，在不同位置之间转移反应容器；所述孵育单元包括旋转装置，所述旋转装置上设置孵育反应容器位，用于孵育反应容器内的反应物；所述处理单元包括处理盘，所述处理盘上设置清洗分离反应容器位和测量反应容器位，分别用于清洗分离反应容器内的反应物和测量反应容器内的反应信号。
根据本发明的再一方面，提供一种样本分析方法，包括：加注步骤，向反应容器内加注样本和试剂；孵育步骤，对孵育单元的反应容器位上的反应容器进行孵育；孵育步骤，对孵育单元的反应容器位上的反应容器内的反应物进行孵育；清洗分离步骤，对处理单元的清洗分离反应容器位上的反应容器内的反应物进行清洗分离；测量步骤，对处理单元的测量反应容器位上的反应容器内的反应信号进行测量；转移步骤，通过转移单元将所述反应容器在所述孵育单元和所述处理单元以及所述处理单元的清洗分离反应容器位、所述处理单元的测量反应容器位之间转移。
本发明的孵育单元实现反应容器内反应物的孵育，独立于孵育单元的处理单元实现反应容器内反应物的清洗分离和对反应容器内的信号进行测量，反应容器在孵育单元和处理单元之间的转移通过转移单元实现。本发明的清洗分离和测量分别在处理盘上的内外圈上实现，不仅省去了单独的清洗分离盘和测量盘，还提高了反应容器转移的可靠性，从而精简了系统结构和控制流程、显著缩减了孵育单元和处理单元尺寸，并通过独立的孵育单元实现灵活的孵育时间。本发明提高了分析装置的工作效率，很好解决了目前自动化仪器体积大、检测速度慢、成本高、性能差等技术难题，不但节约了实验室空间，提高了测试效率，而且有利于减少费用开支，最终节约了大量的自然资源和社会资源。
附图说明
图1是一步法反应模式示意图；
图2是一步法反应模式(另一种信号测量方式)示意图；
图3是延时一步法和两步法反应模式示意图；
图4是本发明自动分析装置的第一种实施方式示意图；
图5是一步法测试流程图；
图6是延时一步法测试流程图；
图7是两步法测试流程图；
图8是本发明自动分析装置的第二种实施方式示意图；
具体实施方式
下面通过具体实施方式结合附图对本发明作进一步详细说明。
本发明的一种自动分析装置，包括：加注单元，加注样本或/和试剂到反应容器；孵育单元，孵育反应容器内的反应物；处理单元，清洗分离反应容器内的反应物并测量反应容器内的反应信号；转移单元，在不同位置之间转移反应容器；所述孵育单元包括旋转装置，所述旋转装置上设置孵育反应容器位，用于孵育反应容器内的反应物；所述处理单元包括处理盘，所述处理盘上设置清洗分离反应容器位和测量反应容器位，分别用于清洗分离反应容器内的反应物和测量反应容器内的反应信号。
反应容器为样本和试剂的反应提供反应场所，可以是各种形状和构造的反应管、反应杯、多个腔的反应杯条、反应芯片等，一般为一次性使用。反应容器的材料通常为塑料，如聚苯乙烯等。反应容器可以在内壁预先包被抗原或抗体，也可不包被，也可在其内预先存放包被好的磁珠或塑料球。反应容器的存储和供给由反应容器供给单元完成。反应容器供给单元主要采用两种主要方式存放和提供反应容器，一种是料仓式，反应容器可以成包散乱倒入反应容器供给单元的料仓中，然后反应容器供给单元自动将反应容器逐次单个排序，供给反应容器到转移单元；另一种方式是预排列式，反应容器预先排列在反应容器托盘、盒或反应容器架、槽道上，反应容器供给单元每次可将整盘、整盒反应容器或一排、一列反应容器输送至目标位置。
反应容器在本发明装置中不同位置之间的转移可由转移单元完成。转移单元可以是任何合适的可以转移或移动反应容器的机构，本发明优选的转移单元主要包括驱动机构、水平运动机械臂、抓放机构等结构。抓放机构通常为机械手指，可以抓放反应容器，水平运动机械臂在驱动机构驱动下可沿着X向、Y向、X向和Y向、径向、周向、径向和周向等方向移动抓放机构，将抓放机构抓取的反应容器移动到不同位置。除了水平运动外，转移单元还可做上下运动，将反应容器放入不同的位置或从不同的位置取出。根据测试速度和整机布局不同，可设置一个或多个转移单元。
加注单元完成样本、试剂的加注。加注单元一般由钢针或一次性吸嘴(Tip)、加注运 动驱动机构、注射器或注液泵、阀、流体管路以及清洗槽(当采用Tip时也可没有清洗槽)等组件构成。为了完成吸取样本、试剂及其加注动作，加注单元除了可以上下运动外，还可以水平运动，水平运动通常有旋转、X向、Y向等几种运动形式及其组合。加注单元可以是一个，既加样本又加试剂，这样可使整机结构更紧凑和成本更低。为了提高测试速度，加注单元还可进一步包括一个或几个样本加注单元、一个或几个试剂加注单元，样本加注单元只加注样本或加注样本和部分试剂，试剂加注单元加注试剂。
为了方便加注单元的加注，本发明还可包括加注站。加注站位于转移单元和加注单元的运动范围内或可通过水平运动运动到转移单元和加注单元的运动范围内。加注站接收和承载转移单元转移过来的反应容器、接受加注单元向反应容器内加注样本和试剂。加注站上设置反应容器位，用于放置需要加注样本和试剂的反应容器。为了使样本和试剂混合更均匀、反应更充分，同时为了精简整机结构和缩小体积，可在加注站集成混匀机构，对每次加注后的反应容器进行超声混匀、偏向旋转或震荡混匀，也可以将混匀机构，比如超声波发生器集成于加注单元，在加注样本和试剂的同时或加注动作完成后由加注单元产生的超声波实现混匀。本领域内技术人员可以理解，加注站也可不集成混匀机构，混匀还可由加注单元的吸排动作或冲击力完成。为了使整机更紧凑，加注站也可整体集成于孵育单元上，这样加注站可以不位于转移单元的轨迹下。
孵育单元孵育反应容器内的反应物。孵育单元主要包括保温装置和旋转装置。孵育单元的保温装置外围通常具有保温棉等隔热材料，通常包裹或包围旋转装置的底部、周边和上部，侧面或底部内侧可设有加热装置和传感器，上部一般为盖板等结构，为孵育单元提供恒温孵育环境。当然，为了传热效率更高，加热装置也可以安装在旋转装置上。孵育单元的旋转装置上设置若干个孔、槽、托架、底座或其他适合承载反应容器的结构，定义为反应容器位。反应容器位是反应容器内的反应物反应孵育的主要场所，使反应容器内的样本分析物和相应的试剂以及试剂和试剂之间相互反应。通常来说，反应容器位越多，可支持的孵育时间就越长，测试速度也越快。为了增加反应容器位同时控制孵育单元尺寸，孵育单元的旋转装置上可设置以旋转装置旋转中心为圆心的至少两圈反应容器位。旋转装置最好为一个，包括驱动、传动机构及相关的控制电路等，控制和带动旋转装置根据测试需要旋转，转送所述反应容器位前进若干位置。旋转装置上的至少一个反应容器位在转移单元的运动范围内，这样转移单元可以将反应容器移入移出孵育单元的旋转装置。
处理单元清洗分离反应容器内的反应物和测量反应容器内的反应信号。处理单元主要包括保温装置、处理盘、清洗分离装置和测量装置。处理单元的保温装置与孵育单元类似，外围通常具有保温棉等隔热材料，通常包裹或包围处理盘的底部、周边和上部，侧面或底 部内侧可设有加热装置和传感器，上部一般为盖板等结构，为处理单元提供恒温孵育环境。当然，为了传热效率更高，加热装置也可以安装在旋转装置上。除了提供恒温环境外，保温装置还可支撑和固定清洗分离装置的磁场产生装置，为清洗分离提供磁场环境。另外，由于需要测量的信号通常为微弱光信号，测试时容易受到环境光的干扰和影响而使测量不准确，保温装置还可为处理单元的测量装置提供测量时所需的密闭的暗室环境。与孵育单元类似，处理盘上设置若干个孔、槽、托架、底座或其他适合承载反应容器的结构，定义为反应容器位，其中用于清洗分离的反应容器位定义为清洗分离反应容器位，用于测量的反应容器位定义为测量反应容器位。处理盘上的反应容器位可设置成以所述处理盘旋转中心为圆心的至少两圈，清洗分离反应容器位分布在至少一圈上，测量反应容器位分布在至少另外一圈上，这样减少清洗分离和测量的相互干扰以及减少处理单元的尺寸和体积。对于需要信号孵育的测试，测量反应容器位除了用于测量外，还可实现信号孵育。通过处理盘的旋转，可把测量反应容器位上的反应容器旋转到测量装置进行测量，从而实现信号孵育。以酶促化学发光的信号孵育为例，若其信号孵育需要5分钟，测量反应容器位可在转送反应容器到测量装置的过程中实现5分钟的信号孵育。处理盘最好为一个，包括驱动、传动机构及相关的控制电路等，控制和带动处理盘每隔固定时间(比如一个循环或周期)旋转固定的角度，转送其上的反应容器位前进若干的位置(比如前进一个反应容器位)。旋处理盘上的至少两个反应容器位在转移单元的运动范围内，这样转移单元可以将反应容器移入移出处理盘。
处理单元除了上述的功能外，其上的清洗分离装置还可对清洗分离反应容器位上的反应容器进行清洗分离，以去除反应物中未结合的成分。本发明处理单元的清洗分离装置包括磁场产生装置和冲洗机构。磁场产生装置提供磁场环境，使反应容器内的顺磁颗粒吸附到反应容器内壁。由于在磁场中的响应时间、移动距离和阻力等因素，顺磁性颗粒吸附到反应容器内壁需要一定的时间，通常为几秒到几十秒不等，这样在每次吸取废液(包括未结合成分)前，反应容器需要经过磁场一段时间。本发明的一种优选实施例中，磁场产生装置可直接安装或固定在处理单元的保温装置，这样不仅可以节省额外的固定机构，降低成本，还可使磁铁产生装置更靠近反应容器位，从而减少顺磁颗粒的吸附时间，提高清洗分离效率。冲洗机构包括吸液和注液装置，抽吸反应容器内的未结合成分和向抽吸后的反应中注入清洗缓冲液。吸液装置包括吸液针、吸液管或吸液嘴等适合抽吸液体的吸液部，吸液部布置在处理单元的上方，可以通过驱动机构的带动进出反应容器位上的反应容器，抽吸反应容器内的未结合成分。注液装置包括注液针、管、嘴等适合排注液体的注液部，注液部同样布置在处理单元的反应容器位的上方，向抽吸后的反应容器内注入清洗缓冲 液。每次冲洗包括一次吸液和一次注入清洗缓冲液和过程，一般冲洗三次或四次，即进行三次或四次冲洗，当然冲洗次数也可灵活多变。为了使清洗更彻底，残留更少，还可在注液位设置混匀器混匀反应容器或利用注液时的冲击力，在注清洗缓冲液同时或注清洗缓冲液后使顺磁性颗粒重悬浮和均匀分散在清洗缓冲液中。处理单元处理盘转送反应容器到清洗分离装置时，清洗分离装置开始对反应容器进行清洗分离。此外，为了精简机构，清洗分离装置还可进一步耦合信号试剂加注机构，在反应容器完成清洗分离后，向其内加注全部或部分信号试剂，比如加注全部的第一、第二信号试剂等或只加注第一信号试剂等，余下的信号试剂可在测量时加注。这样可以充分利用清洗分离装置的功能，缩减了机构体积和节省了成本。清洗分离装置布置在处理单元的处理盘周边或上方，可以直接对处理盘上的反应容器进行清洗分离，这样可以避免设置独立的清洗分离旋转装置，如独立的清洗分离盘或清洗分离轨道等，不仅精简了组件和整机机构，使整机机构更紧凑和成本更低，还避免了反应容器在独立的清洗分离装置和孵育单元之间的转移，使整机控制流程更简单高效，从而提高处理效率和可靠性。
处理单元的测量装置对反应容器内的信号进行测量。信号为反应容器内加入信号试剂后产生的电信号、荧光信号或微弱化学发光信号等。测量装置包括微弱光探测器光电倍增管(PMT)或其他灵敏的光电感应器件，可把测量的光信号转换为电信号，传送至控制中心。此外，为了提高测量效率和保证测量一致性，测量装置还可进一步包括光信号收集和校准等光学装置。本发明的一种优选实施例中，测量装置可以通过通用方式连接或安装到处理单元的保温装置上，比如直接安装固定在保温装置上或通过光纤连接安装到保温装置上，这样可以直接对处理盘测量反应容器位上的反应容器内的信号进行测量，避免设置独立的测量位置或测量盘，可使整机机构更紧凑、成本更低、控制流程更简单高效、处理效率和可靠性更高。此外，为了方便信号试剂的加注，本发明的处理单元还可包括信号试剂加注机构，向处理盘反应容器位上的反应容器内加注信号试剂。本发明的处理单元独立于孵育单元，不仅容易实现清洗分离和测量，还可实现灵活的孵育时间，解决了现有技术整机尺寸过大、结构复杂、孵育时间固定等缺点。
此外，为了输送样本和存储试剂，本发明的自动分析装置还可设置样本输送单元、试剂存储单元等单元。
样本输送单元用于放置待检样本管并将目标样本管输送至吸样本位。样本输送单元有轨道进样、样本盘进样和固定区域进样三种主要方式，样本管通常放置在样本架上，每个样本架一般放置5个或10个样本管，样本架放置于传输轨道上、样本盘上或分析装置的固定区域。
试剂存储单元冷藏试剂并将目标试剂转送至吸试剂位。试剂存储单元通常采用试剂盘和试剂仓两种方式，为了保证试剂的稳定性，试剂盘一般具有制冷功能，如4～10℃。试剂盘上一般设置若干个试剂容器位，用于放置试剂容器。每个试剂容器设置若干个独立的腔体，用于存放不同的试剂组分，如磁微粒试剂、酶标试剂、稀释液等试剂组分。
本发明自动分析装置的第一种实施方式，参考图4。自动分析装置100包括样本输送单元30、试剂存储单元40、加注单元20、反应容器供给单元70、转移单元50、处理单元10、孵育单元80以及加注站90等。下面分别叙述各部分的功能和作用。
样本输送单元30用于放置待检样本管31并将目标样本管输送至吸样本位。本实施例中，样本输送单元30为样本盘，样本盘上放置弧形样本架(图中未标出)上，每个弧形样本架放置10个样本管31。样本盘可在控制中心的控制下由驱动机构带动将目标样本转送至吸样本位，吸样本位位于加注单元20的水平运动轨迹与样本管中心圆的交点处。
试剂存储单元40冷藏试剂容器41并将目标试剂转送至吸试剂位。本实施例中，试剂存储单元40为试剂盘，设置16个试剂位，可容纳16个试剂容器41(或试剂盒、试剂瓶，为表述方便，以下简称试剂瓶)。本实施例中，每个试剂瓶41设置4个腔体41a、41b、41c、41d，可用于存放磁微粒试剂、酶标试剂、稀释液等试剂组分。试剂盘可在控制中心的控制下由驱动机构带动将目标试剂瓶转送至吸试剂位，吸试剂位位于加注单元水平运动轨迹与试剂腔中心圆的交点处，本实施例中，与对应4个试剂组分对应，有4个吸试剂位(图中未标出)。
加注单元20完成样本、试剂的加注。加注单元20的水平运动轨迹与样本盘30上的样本位、试剂盘40上的试剂位、加注站90上的反应容器位分别相交，交点处分别为吸样本位、吸试剂位和加注位。本实施例中，加注单元为单一加样机构，可做上下和水平旋转运动，既加注样本又加注试剂，这样可使整机结构更紧凑和成本更低。加注单元20上还可集成超声波发生器等混匀机构，对每次加注后的反应容器进行超声混匀。其它实施方式中，混匀机构可设置在加注站90上，用于对加注后的反应容器进行超声混匀或震荡混匀。
反应容器供给单元70存放和提供反应容器。本实施例中，为了使整机更为紧凑和成本更低，反应容器供给单元采用预先排列式。反应容器供给单元70包括两个反应容器托盘，反应容器托盘上设置若干数量的反应容器位，存放未使用的反应容器。反应容器供给单元70在转移单元50的水平运动范围内，这样转移单元50可以遍历托盘上每个反应容器位上的未使用的反应容器，为新开始的测试提供未使用的反应容器。
转移单元50可以水平运动，在自动分析装置100的不同位置之间转移反应容器。本实施中，转移单元50设置为1个，可做三维运动，这样可使整机更为紧凑和成本更低。 转移单元50包括X向运动机械臂50b、Y向导轨50a、Y向运动机械臂50c以及垂直运动机构和机械手指(图中未标出)等机构。转移单元50可同时沿着X向、Y向水平移动机械手指，水平运动范围覆盖边界多边形56内的范围，可将反应容器在反应容器供给单元70、加注站90、孵育单元80上的反应容器位、处理单元10上的清洗分离反应容器位11a、测量反应容器位11b、丢反应容器孔60之间转移。
孵育单元80孵育反应容器内的反应物。本实施例中，孵育单元80的保温装置为锅体82和上盖(图中未标出)，旋转装置为孵育盘81。锅体82侧面或底部内侧有加热器和传感器，包围孵育盘81的底部和周边，为孵育单元80提供恒温孵育环境，防止或减少孵育单元80热量的散失。孵育盘81可绕中心轴旋转，其上设置了以旋转中心为圆心的三圈反应容器位81a、81b、81c，当然圈数是可以改变的，比如可以是1圈、2圈、4圈或更多等。
处理单元10独立于孵育单元，对反应容器内的反应物进行清洗分离和对反应容器内的信号进行测量。本实施例中，处理单元10的保温装置为锅体12和上盖(图中未标出)，处理盘为11、清洗分离装置为16、测量装置为86。锅体12侧面或底部内侧有加热器和传感器，包围处理盘11的底部和周边，为处理单元10提供恒温环境和暗室环境，防止或减少孵育单元10热量的散失以及外界杂散光影响。除了提供恒温和暗室环境外，锅体12还支撑和固定清洗分离装置16的磁场产生装置，为清洗分离提供磁场环境。本实施例中，清洗分离装置16的磁铁产生装置为永磁体装置，这样可以提供更强和更稳定的磁场环境。清洗分离装置16的冲洗机构包括吸液装置和注液装置以及混匀机构。清洗分离装置16还可耦合信号试剂加注机构，向完成清洗分离的反应容器内加注全部或部分信号试剂。测量装置86包括微弱光探测器光电倍增管(PMT)，直接安装在锅体82上，对反应容器内加入信号试剂后产生的微弱化学发光信号进行测量。处理盘11可绕中心轴旋转，其上设置了以旋转中心为圆心的两圈反应容器位11a和11b。其中内圈11a上的反应容器位为清洗分离反应容器位，外圈11b上的反应容器位为测量反应容器位，这样不仅有利于清洗分离装置和测量装置的安装，还可减少处理单元的整体尺寸。当然，根据测试的需要，处理盘上反应容器位的圈数是可以改变的，比如可以是1圈、3圈、4圈或更多等。在孵育单元80孵育结束需要清洗分离的反应容器由转移单元50转移到处理盘11内圈11a上的清洗分离反应容器位，处理盘旋转，转送清洗分离反应容器位上的反应容器经过清洗分离装置进行清洗分离。清洗分离完成需要测量的反应容器，由转移单元50从内圈11a上的清洗分离位转移到外圈11b上的测量反应容器位，处理盘旋转，转送测量反应容器位上的反应容器至测量装置进行测量，若反应容器的反应物需要信号孵育，则在转送过程中实现信号孵育。
下面以一个一步法测试为例，结合附图4和5，简述自动分析装置100的测量流程和 步骤。测试开始后，
步骤200加载反应容器：转移单元50从反应容器供给单元70转移一个未使用的反应容器到加注站90的反应容器位上，
步骤201加注样本和试剂：加注单元20分别从吸样本位和吸试剂位吸取样本和试剂加注到加注站90的反应容器位上的反应容器内，
步骤202混匀：若需要混匀，则集成于加注站4的混匀机构对反应容器内的样本和试剂进行混匀。若不需要混匀，则省略该步骤，
步骤203孵育：转移单元50从加注站将加注完样本和试剂的反应容器转移到孵育盘81三圈(81a、81b、81c)的其中一圈的反应容器位，反应容器开始在孵育单元孵育。反应容器在孵育单元81的孵育时间因具体测试项目而异，一般为5～60分钟，
步骤204清洗分离：反应容器孵育完成或孵育一定时间后，转移单元50将其从孵育单元80的反应容器位转移至处理盘11内圈11a上的清洗分离反应容器位，处理盘11每隔固定时间旋转前进1个位置，转送清洗分离反应容器位上的反应容器到清洗分离装置16，经过清洗分离装置16的磁场、由清洗分离装置16的冲洗机构和混匀机构对反应容器完成吸液、注清洗缓冲液、清洗混匀直至完成清洗分离，
步骤205加注信号试剂：清洗分离完成后，处理盘11转送清洗分离反应容器位上的反应容器离开磁场区域，由清洗分离装置16上耦合的信号试剂注液机构向反应容器内注入全部或部分信号试剂。加注完成全部或部分信号试剂后，转移单元50将反应容器从处理盘11内圈11a上的清洗分离反应容器位转移到外圈11b上的测量反应容器位，
步骤206信号孵育：若需要信号孵育，在处理盘11转送外圈11b上的测量反应容器位的反应容器到测量装置86时完成全部或部分信号孵育。若不需要信号孵育，则该步骤省略，
步骤207测量：需要测量的反应容器转送经过测量装置86时，由测量装置86对反应容器内的反应信号进行测量，测量结果经处理后传送至自动分析装置的控制中心，
步骤208丢弃反应容器：转移单元50将测量后的反应容器从处理盘11外圈11b上的测量反应容器位转移至丢弃反应容器孔60丢弃。
参考附图4和附图6，延时一步法测试流程和步骤与一步法试不同之处在于步骤301-305，将试剂分二次分注和增加了一次孵育，其他步骤与一步法类似，不再赘述。
步骤301加注样本和第一试剂：加注单元20分别从吸样本位和吸试剂位吸取样本和第一试剂加注到加注站90上的反应容器内，
步骤302混匀：若需要混匀，则集成于加注站90的混匀器对反应容器内的样本和第 一试剂进行混匀。若不需要混匀，则省略该步骤，
步骤303孵育：转移单元50从加注站4将加注完样本和第一试剂的反应容器转移到孵育盘81三圈(81a、81b、81c)的其中一圈的反应容器位，反应容器开始在孵育单元孵育。反应容器在孵育单元81的孵育时间因具体测试项目而异，一般为5～60分钟，
步骤304加注第二试剂：第一次孵育结束后，转移单元50从孵育单元80的反应容器位将反应容器再次转移至加注站4，加注单元20从吸试剂位吸取第二试剂加注到加注站90上的反应容器内，
步骤305混匀：若需要混匀，则集成于加注站90的混匀器对反应容器内的样本和第一试剂进行混匀。若不需要混匀，则省略该步骤，
参考附图4和附图7，两步法测试流程和步骤与延时一步法试不同之处在于增加了步骤404，增加了一次清洗分离：
步骤404清洗分离：反应容器孵育完成或孵育一定时间后，转移单元50将其从孵育单元80的反应容器位转移至处理盘11内圈11a上的清洗分离反应容器位，处理盘11每隔固定时间旋转前进1个位置，转送清洗分离反应容器位上的反应容器到清洗分离装置16，经过清洗分离装置16的磁场、由清洗分离装置16的冲洗机构和混匀机构对反应容器完成吸液、注清洗缓冲液、清洗混匀直至完成清洗分离，第一次清洗分离完成后，转移单元50将反应容器从处理盘11内圈11a上的清洗分离反应容器位转移至加注站90。加注单元20从吸试剂位吸取第二试剂加注到加注站90上的反应容器内，
两步法其他步骤与延时一步法类似，不再赘述。
由以上描述可见，自动分析装置100采用相互独立的孵育单元和处理单元，孵育单元不受处理单元的影响，可以实现灵活的孵育时间，处理单元同时实现清洗分离和测量，不仅省去了现有技术采用的独立的清洗分离盘和测量盘，缩减了整机尺寸和降低了成本，还精简了测试步骤和降低了控制的复杂度和难度，避免了反应容器在多个盘之间的转移。此外，处理单元通过设置不同的反应容器位，清洗分离装置布置在处理单元内侧，测量装置布置在处理单元外侧，将清洗分离在处理盘内圈的清洗分离反应容器位实现，将测量在处理盘外圈的测量反应容器位实现，不仅排除了清洗分离和测量的相互影响，还缩减了处理单元的尺寸，使整机结构更加紧凑，成本更低，测试效率更高。
除了以上提到的独特优势之外，本发明的自动分析装置还可以灵活拓展和最大限度地复用，实现产品的系列化。在实施例一的基础上，为了进一步提升整机规格参数和测试通量，满足标本量更大的终端客户需求，可以通过增加转移单元和加注单元数量、适当增大孵育单元尺寸或增加孵育单元数量等方式来实现。参考图8为本发明自动分析装置的第二 种实施方式示意图。样本输送单元30采取轨道和样本架的进样方式，这样可以容纳更多样本，可以实时追加样本，操作也更为方便。样本架32和其上的样本管31可被输送到第一加注单元21的运动轨迹下。试剂存储单元40增加了试剂存放位置，可以放置更多试剂容器。加注单元20包括第一加注单元21和第二加注单元22，第一加注单元21加注样本，第二加注单元22加注试剂，第一加注单元21和第二加注单元22的运动轨迹经过孵育单元80的反应容器位，这样加注单元20可将样本和试剂直接加注在孵育单元80反应容器位上的反应容器内，即本实施例中的加注站位于孵育单元上。当然也可增加更多的加注单元，这样提高了加样本和试剂的速度。为了彻底解决样本携带污染问题，本实施例中第一加注单元21采用一次性吸嘴(Tip头)加样，图8中93和96分别为Tip头装载位和Tip头卸载位。反应容器供给单元70除了可以提供新的反应容器外，还可以提供新的Tip头。转移单元50包括可独立做三维运动的第一转移单元51和第二转移单元52，第一转移单元51主要在反应容器供给单元70、孵育单元80、Tip头装载位和Tip头卸载位、反应容器丢弃孔60a等位置之间转移反应容器和Tip头，第二转移单元52主要在孵育单元80、混匀站90和处理单元10以及反应容器丢弃孔60b之间转移反应容器。当然，转移单元可以不止2个，可以根据需要设置更多的转移单元以提高反应容器转移的效率和速度。孵育单元80的旋转装置设置两圈反应容器位81a、81b，处理单元10独立于孵育单元，可以全复用实施例一。处理盘11上的至少一个清洗分离反应容器位和至少一个测量反应容器位在第二转移单元52的运动范围内，这样第二转移单元52可以在孵育单元、混匀站、处理单元之间以及清洗分离反应容器位和测量反应容器位之间转移反应容器。
本领域内普通技术人员应该可以理解，本实施例的测试流程和步骤与实施例一主要不同在于：加注样本和试剂由第一和第二加注单元协调配合完成；样本和试剂的加注都在孵育单元的反应容器位上完成；加注样本或试剂后的反应容器的混匀由独立的混匀站完成；反应容器转移由第一和第二转移单元协调配合完成，其它动作和流程与实施例一相同或相似，参考图5～图7，不再赘述。该实施例与现有技术相比，避免了额外的大尺寸的清洗分离盘和测量盘，同时通过功能不同的反应容器位的分圈分布也减少了处理单元自身的尺寸，从而使整机更为紧凑、成本更低、效率更高和可靠性更好。
本发明实施例还提供了一种样本分析方法，具体包括：
加注步骤，向反应容器内加注样本和试剂；
孵育步骤，对孵育单元的反应容器位上的反应容器进行孵育；
清洗分离步骤，对处理单元的清洗分离反应容器位上的反应容器内的反应物进行清洗分离；
测量步骤，对处理单元的测量反应容器位上的反应容器内的反应信号进行测量；
转移步骤，通过转移单元将所述反应容器在所述孵育单元和所述处理单元以及所述处理单元的清洗分离反应容器位、所述处理单元的测量反应容器位之间转移。
本发明以孵育单元为中心实现反应容器内反应物的孵育，独立于孵育单元的处理单元对清洗分离反应容器位上的反应容器内的反应物进行清洗分离和对测量反应容器位上的反应容器内的信号进行测量，反应容器在孵育单元和处理单元之间的转移以及处理单元不同反应容器位之间的转移通过转移单元的运动实现。本发明不仅提高了反应容器转移的可靠性，省去了单独清洗分离盘和测量盘，精简了系统结构和控制流程，还可以显著缩减处理单元尺寸，使孵育单元实现灵活的孵育时间。本发明提高了分析装置的工作效率，很好解决了目前自动化仪器体积大、检测速度慢、成本高、性能差等技术难题，不但节约了实验室空间，提高了测试效率，而且有利于减少费用开支，减轻受测者负担，最终节约了大量的自然资源和社会资源。
本发明实施例中描述的技术特征或操作步骤可以按照任何合适的方式进行组合。本领域内普通技术人员容易理解，本发明实施例描述的方法中的步骤或动作的顺序是可以改变的。因此，除非另有说明要求一定的顺序，在附图或者详细描述中的任何顺序只是为了用作说明的目的，而不是必须的顺序。
本发明的各实施例中可以包括各种步骤，这些步骤可以体现为可由通用或专用计算机(或其它电子设备)执行的机器可执行的指令。可选地，这些步骤可以由包括了用以执行这些步骤的特定逻辑电路的硬件元件执行或者由硬件、软件和/或固件联合执行。
以上通过具体的实施例对本发明进行了说明，但本发明并不限于这些具体的实施例。本领域技术人员应该明白，还可以对本发明做各种修改、等同替换、变化等等，这些变换只要未背离本发明的精神，都应在本发明的保护范围之内。此外，以上多处所述的“一个实施例”“本实施例”等表示不同的实施例，当然也可以将其全部或部分结合在一个实施例中。
以上所述实施例仅表达了本发明的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对本发明专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。因此，本发明专利的保护范围应以所附权利要求为准。

Claims (10)

  1. 一种自动分析装置，其特征在于:包括：
    加注单元，加注样本或/和试剂到反应容器；
    孵育单元，孵育反应容器内的反应物；
    处理单元，清洗分离反应容器内的反应物并测量反应容器内的反应信号；
    转移单元，在不同位置之间转移反应容器；
    所述孵育单元包括旋转装置，所述旋转装置上设置孵育反应容器位，用于孵育反应容器内的反应物；所述处理单元包括处理盘，所述处理盘上设置清洗分离反应容器位和测量反应容器位，分别用于清洗分离反应容器内的反应物和测量反应容器内的反应信号。
  2. 根据权利要求1所述的自动分析装置，其特征在于，所述转移单元将所述反应容器在所述孵育单元和所述处理单元之间转移。
  3. 根据权利要求1所述的自动分析装置，其特征在于，所述转移单元还将所述反应容器在所述处理单元的清洗分离反应容器位、所述处理单元的测量反应容器位之间转移。
  4. 根据权利要求1所述的自动分析装置，其特征在于，所述处理盘包括以所述处理盘旋转中心为圆心的至少两圈反应容器位，所述清洗分离反应容器位分布在其中至少一圈上，所述测量反应容器位分布在至少另外一圈上。
  5. 根据权利要求4所述的自动分析装置，其特征在于，所述处理盘包括以所述处理盘旋转中心为圆心的内圈和外圈反应容器位，所述清洗分离反应容器位分布在内圈上，所述测量反应容器位分布在外圈上。
  6. 根据权利要求1的自动分析装置，其特征在于，所述孵育单元的旋转装置上的反应容器位分布在以所述旋转装置旋转中心为圆心的至少两圈上。
  7. 根据权利要求1的自动分析装置，其特征在于，所述处理单元包括清洗分离装置，对所述清洗分离反应容器位上的反应容器进行清洗分离，以去除反应物中未结合的成分。
  8. 根据权利要求1的自动分析装置，其特征在于，所述处理单元包括测量装置，所述测量装置安装在所述处理单元上，对所述测量反应容器位上的反应容器内的反应信号进行测量。
  9. 根据权利要求1所述的自动分析装置，其特征在于：所述处理盘上的测量反应容器位还具有信号孵育功能。
  10. 一种样本分析方法，其特征在于：包括
    加注步骤，向反应容器内加注样本和试剂；
    孵育步骤，对孵育单元的反应容器位上的反应容器内的反应物进行孵育；
    清洗分离步骤，对处理单元的清洗分离反应容器位上的反应容器内的反应物进行清洗分离；
    测量步骤，对处理单元的测量反应容器位上的反应容器内的反应信号进行测量；
    转移步骤，通过转移单元将所述反应容器在所述孵育单元和所述处理单元以及所述处理单元的清洗分离反应容器位、所述处理单元的测量反应容器位之间转移。
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