Patent Description:
Automatic immunoassay is based on immunological reactions in which antigen and antibody bind to each other, relates the optical or electrical signal to the analyte concentration through a series of cascade amplification reactions by labeling the antigen antibody with the enzyme label, lanthanide label or chemiluminescent agent, to analyze the antigen or antibody to be tested in the human sample, which is mainly applied in the clinical lab of the hospital, the third-party independent laboratory, the blood test center, etc., to perform quantitative, semi-quantitative or qualitative testing of the contents of various analytes in human body fluid, so as to diagnose the infectious disease, tumor, endocrine function, cardiovascular disease, prenatal and postnatal care, and the autoimmune disease. Further prior art analyzing apparatus or incubation analyzing apparatus are disclosed in the following documents: <CIT>, <CIT>, <CIT> and <CIT>. In particular, <CIT> discloses a data carrier for use with a diagnostic instrument comprising a disk containing slots to move the containers along the process part.

Referring to <FIG>, the immunoassay can be generally divided into one-step protocol, time-delay one-step protocol, two-step protocol according to the test protocols. The main test steps generally include dispensing sample and reagent, mixing the reactants, incubating, and washing and separating (Bound-Free, referred to as B/F or washing for short), dispensing a signal reagent, measuring, etc. The incubation of the present disclosure specifically refers to the process of antigen-antibody binding reaction or biotin-avidin binding reaction of the reactants in the reaction vessel in a constant temperature environment of the reaction unit before the start of bound-free of the reaction vessel. Specifically, one-step protocol performs the incubation once, i.e., one incubation before entering the bound-free; time-delay one-step protocol performs the incubation twice, including a first incubation before the dispensing a second reagent and a second incubation before entering the bound-free; and the two-step protocol performs the incubation twice, including a first incubation before the first bound-free and a second incubation before a second bound-free. The test steps corresponding to different test protocols are detailed as follows.

In the incubation steps of the above flow, the existing specific implementation technique solution are generally divided into two manners: fixed-time incubation and variable-time incubation. In the fixed-time incubation manner, all incubation testing time of each testing protocol are the same, for example, all one-step tests can only implement <NUM> minutes of incubation, and all two-step tests can only implement <NUM> minutes of the first incubation and <NUM> minutes of the second incubation, etc. Due to differences of a specific assay in the reagent material, formulation, production process, reaction principle and condition, such fixed-time incubation may increase the difficulty of the reagent development or sacrifice some test performances during the actual development and testing, such as sensitivity, etc., and thus is difficult to adapt to multiple different assays. Contrary to the constraints and limitations of the fixed-time incubation method on the reagent development and performance, the variable-time incubation method is flexible and adaptable, and can set the incubation time for different flexibility of each assay, i.e., each assay can implement its own optimum incubation time. The variable-time incubation method can reduce the constraint on the reagent development and gives full play to the performance of the reagent. In order to implement the variable-time incubation, the existing technical solution generally adopts an independent incubation tray only for implementing the incubation. The incubation tray needs multiple times of rotating and stopping in one test cycle, and the angle of each rotation is determined according to the incubation time. This technical solution has the disadvantages of complicated control, difficult technical implementation and unsuitable for high-speed automated testing and so on.

In order to solve the deficiencies and problems ubiquitous in the prior art, the present disclosure provides a reaction incubation apparatus, according to claim <NUM>, which is simple and reliable in control, flexible and efficient in the incubation flow and method, and an immunoassay analyzer having the reaction incubation apparatus, and also provides a reaction incubation method according to claim <NUM>.

According to claim <NUM>, the reaction incubation apparatus includes: a reaction unit configured to carry and incubate a reaction vessel; a transferring unit configured to transfer the reaction vessel into or out of the reaction unit; in which the reaction unit includes a rotating apparatus provided with an incubation position, the incubation position is advanced by a predetermined angle θ at an interval of fixed time T with the rotating apparatus; the transferring unit transfers the reaction vessel out of the incubation position according to a variable incubation time t<NUM>; characterized in that the reaction incubation apparatus further comprises a bound-free (B/F) apparatus, the rotating apparatus is a reaction tray, the B/F apparatus is disposed above the reaction tray, to directly wash and separate the reaction vessel on the reaction tray, wherein the reaction tray is rotatable about a central axis and is provided with four circles of reaction vessel positions centered on the center of rotation.

According to another aspect of the disclosure, an immunoassay analyzer is provided with the reaction incubation apparatus.

According to claim <NUM>, the reaction incubation method includes: a transferring-in step: a transferring unit transfers a reaction vessel containing reactants into an incubation position of a reaction unit; an incubating step: the reaction vessel is carried forward by a predetermined angle θ at an interval of fixed time T in the incubation position with a rotating apparatus, and incubated for a variable incubation time t<NUM>=(Ω/θ)T; where the Ω is a total forward angle of the reaction vessel in the incubation position with the rotating apparatus, and the Ω is an integer multiple of the θ; a transferring-out step: the transferring unit transfers the reaction vessel out of the incubation position of the reaction unit after an incubation time t<NUM>; a B/F step: when the reaction tray of the reaction unit transfers the reaction vessel to a B/F apparatus disposed above the reaction tray, starting, by the B/F apparatus to wash and separate the reaction vessel, wherein the reaction tray is rotatable about a central axis and is provided with four circles of reaction vessel positions centered on the center of rotation.

The reaction incubation apparatus of the disclosure is carried forward by a predetermined angle θ at an interval of fixed time T, and the transferring unit transfers the reaction vessel out of the incubation position according to the variable incubation time t1. The disclosure can not only implement flexible and variable incubation time and make the control simple and efficient, but also simultaneously implement washing and/or measuring on the reaction incubation apparatus, such that the structure of the immunoassay analyzer is more simple, reliable, compact and the cost is lower, thereby effectively solving the problems in the prior art that in order to implement the variable incubation time, the control is complicated, the reliability is low, the high-speed automation is difficult to implement, and the washing and/or measuring cannot be simultaneously implemented.

The present disclosure will be further described in detail below through embodiments with reference to the accompanying drawings.

A reaction incubation apparatus provided by the present disclosure includes: a reaction unit configured to carry and incubate a reaction vessel; and a transferring unit configured to move the reaction vessel into and out of the reaction unit. The reaction unit includes a rotating apparatus provided with an incubation position. The incubation position is advanced by a predetermined angle θ at an interval of fixed time T with the rotating apparatus. The transferring unit moves the reaction vessel out of the incubation position according to a variable incubation time t1. The reaction incubation apparatus further comprises a bound-free (B/F) apparatus, the rotating apparatus is a reaction tray, the B/F apparatus is disposed above the reaction tray, to directly wash and separate the reaction vessel on the reaction tray, wherein the reaction tray is rotatable about a central axis and is provided with four circles of reaction vessel positions centered on the center of rotation. An example of a reaction incubation apparatus not being part of the present invention is described with reference to <FIG>. The reaction incubation apparatus <NUM> mainly includes a reaction unit <NUM> (including a rotating device and a heat preservation device), a transferring unit <NUM>, and the like. The function and role of each part are respectively described below.

The reaction unit <NUM> carries and incubates a reaction vessel containing the reactant. The reaction unit <NUM> mainly includes the heat preservation device and a rotating device. The periphery of the heat preservation apparatus usually has a heat insulating material such as heat preservation cotton, and a heating apparatus and a sensor may be disposed on the side or the bottom inside of the heat preservation apparatus, and the upper portion thereof is generally a cover plate structure, etc., to provide a constant temperature incubation environment for the reaction unit and prevent or reduce heat loss of the reaction unit. Of course, for higher heat transferring efficiency, the heating apparatus can also be mounted on the rotating apparatus. Preferably, the number of the rotating apparatus is one, which includes a driving mechanism, a transmission mechanism and an associated control circuit, etc., to control and drive the rotating apparatus to rotate by a predetermined angle θ at an interval of fixed time (such as a cycle or a cycle T), and carry the reaction vessel forward by a certain position (such as advancing by a reaction vessel position). The rotating apparatus is provided with a plurality of independent holes, periods, brackets, bases or other structures suitable for carrying the reaction vessels, which are defined as the reaction vessel positions. In the present disclosure, the heat preservation apparatus of the reaction unit <NUM> is a pot body <NUM> and an upper cover (not shown), and the rotating apparatus is a reaction tray <NUM>. The reaction tray <NUM> is rotatable about a central axis, and is provided with four circles of reaction vessel positions (11a, 11b, 11c, 11d) centered on the center of rotation. Of course, the number of the circle can be changed, for example, one circle, two circles, <NUM> or more circles, etc. each circle is provided with several reaction vessel positions, and the number of the reaction vessel positions on each circle may be the same or different. In this example, <NUM> reaction vessel positions are provided at each cycle, and the reaction vessel positions on the four cycles are all incubation positions for receiving and incubating the reaction vessels containing the reactants. In order to indicate a physical position of some reaction vessel on the rotating apparatus at a certain time, an absolute coordinate system is set, and the number is progressively increased counterclockwise as <NUM>, <NUM>, <NUM>.

The transferring unit <NUM> transfers the reaction vessel between different positions of the reaction incubation apparatus <NUM>. The transferring unit can be any suitable mechanism which can transfer or move the reaction vessel. The preferred transferring unit of the present disclosure mainly includes a driving mechanism, a horizontal movement mechanical arm, a gripping-releasing mechanism, and the like. The gripping-releasing mechanism is usually mechanical fingers, which can grip and release the reaction vessel. The horizontal movement mechanical arm can be driven by the driving mechanism to move the gripping-releasing mechanism 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, etc., so as to move the reaction vessel caught by the gripping-releasing mechanism to different positions. In addition to the horizontal movement, the transferring unit <NUM> can also move up and down, to place the reaction vessels in different positions or taking them out of the different positions. According to the different testing speed and overall layout, one or more transferring units may be provided. In the example, one transferring unit <NUM> is provided, which can do three-dimensional motion, such that whole apparatus is more compact and the cost is lower. The transferring unit <NUM> includes an X-direction movement mechanical arm 20a, a Y-direction movement mechanical arm 20b, a Y-direction guide rail 20c, a vertical movement mechanism and mechanical fingers (not shown). The transferring unit <NUM> can simultaneously move the mechanical fingers horizontally along the X direction and the Y direction, and the horizontal movement range covers a range within a boundary rectangle <NUM>, i.e., all the reaction vessel positions (incubation positions) on the reaction tray <NUM> are within the horizontal movement range of the transferring unit <NUM>. In this way, the transferring unit <NUM> can implement the flexible incubation time through placing the reaction vessels in different incubation positions or transferring the reaction vessels out of different incubation positions.

The reaction tray <NUM> is rotated by a predetermined angle θ (in the present example, θ = <NUM> degrees) at an interval of fixed time T (in the present example, T = <NUM>, which is a time of one test cycle), and can be rotated counterclockwise or clockwise, for example, rotated by <NUM> degrees counterclockwise every <NUM> seconds and advanced by one reaction vessel position. As for the time sequence of actions of the reaction tray, reference is made to <FIG>, Tm and Tn respectively represent the m-th test cycle and the n-th test cycle, and the reaction tray <NUM> is rotated and advanced during the time cycle C<NUM>-T and stopped at other times. The transferring unit <NUM> can move the reaction vessel into or out of the incubation position on the reaction tray <NUM> in the stop time period after each rotation of the reaction tray <NUM>. The transferring unit <NUM> places the reaction vessel in the incubation position in a time period of C<NUM> to C<NUM> and moves the reaction vessel out of the incubation position in a time period of C<NUM> to C<NUM>. In the present example, C<NUM>=C<NUM>-C<NUM>=<NUM> minutes, which is a time difference between moving the reaction vessel in and out of the incubation position on the reaction tray in one test cycle, which is usually a constant. If a certain reaction vessel containing a reactant is placed in a certain reaction vessel position of the reaction tray in the time period C<NUM> to C<NUM> of the Tm cycle, and the reaction vessel is moved out of the reaction vessel position in period C<NUM> to C<NUM> of the n-th test cycle Tn, then the incubation time is t<NUM>=(Ω/θ)T+C<NUM>=((m-n)θ/θ)T+C<NUM>=(m-n)T+C<NUM>.

In the following description, a one-step protocol test for <NUM> minutes of incubation is taken as an example, and the reaction incubation flow and steps of the reaction incubation apparatus <NUM> are briefly described with reference to <FIG>.

Step <NUM>: the transferring unit moves the reaction vessel into the incubation position. In the stop time period (time C<NUM> to C<NUM>) while the reaction tray <NUM> stops rotating, the transferring unit <NUM> transfers the reaction vessel containing the reactant to an incubation position at an absolute positions <NUM>, which may be located in any one of the four circles, for example, the incubation position on the outer circle 11d at the absolute position <NUM> is selected.

Step <NUM>: reaction vessel incubation time t1. The reaction vessel is rotated counterclockwise by a predetermined angle θ=<NUM>° with the reaction tray <NUM> every cycle T=<NUM> seconds, and carried forward by one reaction vessel position. After <NUM> cycles T, the total angle Ω of the reaction vessel in the incubation position carried forward with the rotating apparatus is <NUM>° at the absolute position <NUM>, and the implemented incubation time is t<NUM>=(Ω/θ) T+C<NUM>=<NUM>+<NUM> = <NUM> minutes. In this example, the constant C<NUM> = <NUM> minutes.

Step <NUM>: the transferring unit moves the reaction vessel out of the incubation position. After the incubation time t<NUM>, the transferring unit <NUM> moves the reaction vessel containing the reactant out of the incubation position on the outer circle 11d at the absolute position <NUM> within the stop time period (time C<NUM> to C<NUM>) during which the reaction tray stops rotating.

Those skilled in the art should be understood that, as for the one-step delay protocol and two-step protocol that require two incubations, the variability of each incubation time can be implemented in accordance with a similar flow and method.

As can be seen from the above description, in the present example, the variable incubation time implemented in the incubation position is t<NUM>=(Ω/θ)T+C<NUM>, where Ω is the total angle of the reaction vessel in the incubation position carried forward with the rotating apparatus, and Ω is an integral multiple of θ, C<NUM> is a constant no greater than T. In particular, in the present example, in order to implement longer incubation time, the total angle Ω of the reaction vessel in the incubation position on the reaction tray carried forward with the reaction tray includes a value greater than <NUM>°, i.e., the variable incubation time t<NUM> includes a value greater than (<NUM>°/θ) T. In this way, the reaction vessel is rotated and carried forward in the incubation position with the reaction tray, and the transferring unit moves the reaction vessel into or out of the incubation position on the reaction tray at a different position, thereby implementing a flexible and variable incubation time.

As can be seen from the above description, in the present example, the reaction tray is advanced by a predetermined angle at an interval of fixed time, to transfer the incubation position thereon to different positions. The horizontal movement range of the transferring unit covers all the incubation positions on the reaction tray, and can move the reaction vessel in or out of the incubation position from different positions. Through this layout and coordinated action of the transferring unit and the reaction tray, not only flexible incubation time can be implemented, but also the multiple rotating and stopping and the uncertainty of each rotating angle of the reaction tray in one cycle in the prior art can be avoided, thereby reducing the control difficulty and complexity, and improving the testing efficiency of the whole apparatus.

As for a first embodiment of the invention, reference is made to <FIG>. The main difference between the first embodiment and the above example, not being part of the present invention, is that the reaction incubation apparatus <NUM> is further provided with a bound-free (B/F) apparatus <NUM> and a measuring apparatus <NUM>. In addition, in the example, not being part of the invention, the reaction vessel positions of four circles of the reaction unit are incubation positions; however, in the first embodiment, only the reaction vessel positions of the inner three circles are the incubation positions to mainly implement the incubation function, and the reaction vessel positions of the outer circle mainly implements the washing and measuring function. It should be noted that the reaction vessel positions of the outer circle can implement partial incubation function "by the way" in the process of the carrying the reaction vessels to the B/F and measuring apparatus. In addition to provide an incubation environment, the heat preservation apparatus of the present embodiment can further support and fix a magnetic field generating apparatus of the B/F apparatus <NUM> to provide a magnetic field environment for the washing. In addition, the heat preservation apparatus can not only provide the mounting position for the measuring apparatus <NUM>, but also implement the darkroom environment required by the measuring apparatus <NUM>. The B/F apparatus <NUM> includes a magnetic field generating apparatus and a flushing mechanism. The magnetic field generating apparatus provides a magnetic field environment for adsorbing paramagnetic particles in the reaction vessel to the inner wall of the reaction vessel. Due to factors such as response time, moving distance and resistance in the magnetic field, it takes a certain time for the paramagnetic particles to adsorb to the inner wall of the reaction vessel, usually ranging from several seconds to several tens of seconds, so that before draining the waste liquid (including unbound component) each time, the reaction vessel needs to pass through the magnetic field for a period of time. Preferably, the magnetic field generating apparatus of the present disclosure can be directly mounted or fixed on the heat preservation apparatus of the reaction unit, thereby not only saving additional fixing mechanism, reducing the cost, but also bringing the magnetic field generating apparatus closer to the reaction vessel position, thereby reducing adsorption time of the paramagnetic particles and improving the washing efficiency. The flushing mechanism includes a liquid drawing and injecting apparatus, in which the liquid drawing apparatus draws the unbound components in the reaction vessel and the liquid injecting apparatus injects a washing buffer into the reaction after the drawing. The liquid drawing apparatus includes a liquid drawing part suitable for drawing the liquid, such as a liquid drawing needle, a liquid drawing tube or a liquid drawing nozzle, and the liquid drawing part is arranged above the reaction unit, and can be driven into and out of the reaction vessel in the reaction vessel position through the driving mechanism to draw the unbound components in the reaction vessel. The liquid injecting apparatus includes a liquid injecting part suitable for discharging the liquid, such as a liquid injecting needle, a liquid injecting tube, a liquid injecting mouth and the like, and the liquid injecting part is also arranged above the reaction vessel position of the reaction unit, and injects the washing buffer into the reaction vessel after the drawing. Each flushing includes a process of a single drawing of liquid and a single injecting of the washing buffer. Usually the flushing is performed three or four times, i.e., three or four flushing, of course the times of the flushing can be varied. In order to make the cleaning more thorough and less residue, it is also possible to dispose a mixer in the liquid injecting position to mix the reaction vessel, or use the impact force to make the paramagnetic particles resuspended and uniformly dispersed in the washing buffer when or after injecting the washing buffer. When the reaction tray of the reaction unit transfers the reaction vessel to the B/F apparatus <NUM>, the B/F apparatus <NUM> starts to wash and separate the reaction vessel. In addition, in order to simplify the mechanism, the B/F apparatus <NUM> may further be coupled with a signal reagent dispensing mechanism so as to add all or part of the signal reagents after completing the washing of the reaction vessel, for example, all the first and second signal reagents are added, or only the first signal reagent is added, etc., and the remaining signal reagents can be added when performing the measurement. This can make full use of the function of the B/F mechanism, reduce the volume of the mechanism and save the cost. It can be seen from the above description that the B/F apparatus <NUM> is disposed around the reaction tray of the reaction unit or above the reaction tray, and can directly wash and separate the reaction vessel on the reaction tray of the reaction unit, so as to avoid disposing an independent B/F rotating apparatus, such as an independent B/F carousel or B/F rail, etc., thus not only the components and the whole apparatus are simplified such that the whole apparatus is more compact and the cost is lower, but also the transferring of the reaction vessel between the independent B/F apparatus and the reaction unit is avoided such that the control flow of the immunoassay analyzer is simpler and more efficient, thereby increasing the processing efficiency and reliability.

The measuring apparatus <NUM> measures the signal in the reaction vessel. The signal is an electrical signal, a fluorescent signal or a weak chemiluminescence signal generated after adding the signal reagent into the reaction vessel. The measuring apparatus <NUM> includes a weak photodetector photomultiplier tube (PMT) or other sensitive photo-sensing apparatus that can convert the measured optical signal into an electrical signal and transmit the electrical signal to the control center. Furthermore, in order to improve the measurement efficiency and ensure the measurement uniformity, the measuring apparatus <NUM> may further include optical apparatus such as optical signal collecting and calibrating apparatus. The weak chemiluminescence signal is taken as an example, in order to avoid the interference of the ambient light, the measuring apparatus <NUM> of the present disclosure is mounted in a reaction unit to measure a reaction signal in a reaction vessel position of the reaction unit. This may make full use of the reaction vessel position on the reaction unit, to make the whole apparatus more compact and the cost less.

According to the test condition, the reaction vessel needed to be incubated is first incubated in the incubation position of the third inner circles 11a, 11b, 11c for a certain time or after completing the incubation, and then transferred to the outer circumference of the reaction tray for washing and measuring or transferred to a position other than the reaction incubation apparatus <NUM> to perform the corresponding operation. It should be noted that the reaction vessel can complete the incubation on the three inner circles 11a, 11b, 11c, and then the reaction vessel is transferred to the outer circle 11d for washing, or after completing a certain cycle of incubation on the three inner circles 11a, 11b, 11c, for example, the incubation for the most of time is completed, then transferred to the outer circle 11d, and then the incubation for the remaining time is completed during the process of transferring the reaction tray to the magnetic separation apparatus. In the former implementation, the outer circle 11d does not require an additional reaction vessel position for the incubation, which allows the reaction tray to be smaller in size and lower in cost. For the latter implementation, for example, if a tested reaction vessel needs to be incubated for twenty-five minutes, it is possible to complete the incubation for the most of time, such as <NUM> minutes, on one or several circles of the three inner circles 11a, 11b, and 11c, and then the reaction vessel is transferred to the outer circle 11d and the incubation for the remaining <NUM> minute is completed before transferring to the B/F unit. This kind of solution can appropriately reduce the number of incubation positions on the three inner circles because the outer circle shares a portion of the incubation function, thereby balancing the number of incubation positions on the inside and outer circles, so as to optimize the size of the reaction tray and fully utilize the internal space of the reaction tray.

It should be understood by those skilled in the art that the reaction incubation flows and steps of the present embodiment are similar to those of the example not being part of the invention. Similarly, with reference to <FIG>, a test of incubation for <NUM> minutes is taken as an example to describe the reaction incubation flows and steps of the reaction incubation apparatus <NUM>.

Step <NUM>: the transferring unit transfers the reaction vessel into the incubation vessel: in the stop period of time (time C<NUM> to C<NUM>) during which the reaction tray <NUM> stops rotating, the transferring unit <NUM> transfers the reaction vessel containing the reactant to the incubation position at the absolute position <NUM>, which may be any one of the three inner circles, such as the incubation position on the inner circle 11a at the absolute position <NUM> is selected.

Step <NUM>: the reaction vessel is incubated for time t<NUM>: the reaction vessel is rotated counterclockwise by a predetermined angle θ=<NUM>° every cycle T=<NUM> seconds with the reaction tray <NUM>, and is carried forward by one reaction vessel position. After twelve cycles of T, the reaction vessel in the incubation position is carried forward by a total angle Ω=<NUM>° with the rotating apparatus to the absolute position <NUM>, and the implemented incubation time is t1=(Ω/θ)T+C<NUM>=<NUM>+<NUM>= <NUM> minutes. In this embodiment, the constant C<NUM> = <NUM> minutes.

Step <NUM>: The transferring unit transfers the reaction vessel out of incubation position: after the incubation time t<NUM>, the transferring unit <NUM> transfers the reaction vessel containing the reactants out of the incubation position on the inner circle 11a at the absolute position <NUM> in the stop period of time (time C<NUM> to C<NUM>) during which the reaction tray stops rotating.

If the incubation is performed for time t<NUM> or the incubation is completed, the test requires washing and measuring, then the transferring unit <NUM> transfers the reaction vessel to the reaction vessel position on the outer circle 11d at the absolute position <NUM>. According to different test conditions, the reaction vessel can continue to be incubated for time t<NUM> (t<NUM>≥<NUM>, which is the incubation time of the reaction vessel implemented in other position other than the incubation position of the rotating apparatus) on the outer circle 11d before transferring to the B/F apparatus <NUM>, or is no longer incubated but directly transferred to the B/F apparatus <NUM>. In this embodiment, after the transferring unit <NUM> transfers the reaction vessel to the reaction vessel position on the outer circle 11d at the absolute position <NUM> and after two more cycles, the reaction vessel passes through the B/F apparatus <NUM>, so the implemented incubation time on the outer circle 11d is t<NUM> = <NUM> seconds. Therefore, the total incubation time that can be implemented by the automatic reaction incubation apparatus <NUM> of the present embodiment is t=t<NUM>+t<NUM>=<NUM> minutes. After the completion of the incubation, the reaction vessel is transferred under the rotation of the reaction tray <NUM> to pass through the B/F apparatus <NUM> and subjected to multi-stage washing by the B/F apparatus <NUM>; and when passing through the measuring apparatus <NUM> under the rotation of the rotating tray, the measuring apparatus <NUM> measures the signal in the reaction vessel. It should be noted that, in other embodiments, after transferring the reaction vessel out of the incubation position but before passing into the B/F apparatus <NUM>, the incubation may not be continued, then the total incubation time is t=t<NUM>=<NUM> minutes.

Those skilled in the art may appreciate that for the one-step delay and two-step protocol that requires two incubations, this embodiment can also implement the variability of each incubation time in a similar manner.

As can be seen from the above description, in the present embodiment, the variable incubation time implemented by the incubation position of the reaction tray is t<NUM>=(Ω/θ)T+C<NUM>, where Ω is the total forward angle of the reaction vessel in the incubation position with the rotating apparatus, and Ω is an integer multiple of θ, and C<NUM> is a constant not greater than T. In particular, in the present embodiment, in order to implement a longer incubation time, the total forward angle Ω of the reaction vessel in the incubation position of the reaction tray with the rotating apparatus includes a value greater than <NUM>°, i.e., the variable incubation time t<NUM> includes a value greater than (<NUM>°/ θ) T. In this way, the reaction vessel is carried forward in the incubation position with the rotation of the reaction tray, and the transferring unit transfers the reaction vessel into or out of the incubation position of the reaction tray from different positions, thereby implementing a flexible and variable incubation time.

A second embodiment of the present disclosure is shown in <FIG>. This embodiment differs from the first embodiment mainly in the transferring unit <NUM> and the B/F apparatus <NUM>. In the present embodiment, the number of the transferring unit <NUM> is one, which can perform longitudinal horizontal and vertical two-dimensional movement, such that the whole apparatus is more compact and the cost lower. The transferring unit <NUM> includes a mechanism such as a Y-direction guide rail 20b, a Y-direction movement mechanical arm 20a, a vertical movement mechanism and mechanical fingers (not shown) and the like. The transferring unit <NUM> can move the mechanical fingers horizontally along the Y direction, and the horizontal movement track is <NUM>, i.e., the reaction vessel position at the absolute position <NUM> on the reaction tray <NUM> is in the horizontal movement range of the transferring unit <NUM>, so that the transferring unit <NUM> can place the reaction vessel into or transfer the reaction vessel out of the reaction vessel position at the absolute position <NUM>. In the present embodiment, the B/F apparatus <NUM> is arranged on the inner circle of the reaction unit, which not only makes the B/F apparatus more compact, but also reduces the adverse effects such as temperature fluctuation, interference due to introduction of ambient light, etc., on the measurement caused by the B/F apparatus.

In the embodiment, the reaction vessel positions on the middle two circles 11b, 11c are the incubation positions, which mainly implement the incubation function. The reaction vessel position on the inner circle 11a mainly implements the function of washing. The reaction vessel position on the outer circle 11d mainly implements the function of measurement. Of course, the reaction vessel position on the inner circle 11a can also implement part of the incubation function in the process of transferring the reaction vessel to the B/F apparatus. During the test, the reaction vessel to be incubated is first transferred by the transferring unit <NUM> into one of the middle two circles 11b, 11c, after the incubation is completed or the incubation is performed in a certain period of time and the washing is required, the reaction vessel is transferred out of the middle two circles 11b, 11c and then into the inner circle 11a by the transferring unit <NUM>; through the rotating transference of the reaction tray, the B/F apparatus <NUM> perform the multi-stage washing on the reaction vessel; when the washing is completed, the reaction vessel is transferred out of the inner circle 11d by the transferring unit <NUM>; if the measurement is required, the transferring unit <NUM> transfers the reaction vessel into the outer circle 11d; and the reaction vessel is transferred to the measuring apparatus for measurement under the rotation of the reacting tray.

It should be appreciated by those skilled in the art that other units of the embodiment are the same as or similar to the first embodiment. The incubation flows and steps of the embodiment are described with reference to <FIG>, through taking a test of <NUM> minutes of incubation as an example to briefly describe the incubation flows and steps of incubation apparatus <NUM>.

Step <NUM>: the transferring unit transfers the reaction vessel into the incubation position: in the stop period of time (time C<NUM> to C<NUM>) during which the reaction tray <NUM> stops rotating, the transferring unit <NUM> transfers the reaction vessel containing the reactants to the incubation position at the absolute position <NUM>, which may be one of the middle two circles 11b, 11c, for example, the incubation position on the middle circle 11c at the absolute position <NUM> is selected.

Step <NUM>: the reaction vessel is incubated for the time t<NUM>: the reaction vessel is rotated counterclockwise by a predetermined angle θ=<NUM>° every cycle T=<NUM> seconds with the reaction tray <NUM>, and is carried forward by one reaction vessel position. After thirty cycles of T, the total forward angle of the reaction vessel at the incubation position with the reaction tray is Ω=<NUM>°, i.e., the reaction vessel goes back to the absolute position <NUM>, and the implemented incubation time is t<NUM>=(Ω/θ)T+C<NUM>=<NUM>+<NUM>= <NUM> minutes. In this embodiment, the constant C<NUM> = <NUM> minutes.

Step <NUM>: the transferring unit transfers the reaction vessel out of the incubation position: after the incubation is performed for the time t<NUM>, the transferring unit <NUM> transfers the reaction vessel containing the reactants out of incubation position on the middle circle 11c at the absolute position <NUM> during the (time C<NUM> to C<NUM>).

If the incubation is performed for the time t<NUM> or the incubation is completed and the test requires washing and measuring, the transferring unit <NUM> first transfers the reaction vessel to the inner circle 11a at the absolute position <NUM> for washing, and after thirty cycles of T, to the outer circle 11d at the absolute position <NUM> for measuring. According to different test conditions, the reaction vessel can continue to be incubated for time t<NUM> on the inner circle (t<NUM> ≥ <NUM>, which is the incubation time implemented by the reaction vessel at a position other than the incubation position of the rotating apparatus) before being transferred to the B/F apparatus <NUM>, or the reaction vessel is no longer incubated but directly transferred to the B/F apparatus <NUM>. In this embodiment, after the transferring unit <NUM> transfers the reaction vessel to the inner circle 11a at the absolute position <NUM> and after one more cycle, the reaction vessel passes through the B/F apparatus <NUM>, thus the implementable incubation time on the inner circle 11a is t<NUM> = <NUM> seconds. The total incubation time that can be implemented by the reaction incubation apparatus of this example is t = t<NUM> + t<NUM> = <NUM> minutes. After the incubation is completed, the reaction vessel is transferred under the rotation of the reaction tray and passes through the B/F apparatus <NUM>, the B/F apparatus <NUM> performs the multi-stage washing on the reaction vessel. When the reaction vessel is transferred back to the reaction vessel position on the inner circle 11a at the absolute position <NUM> after completing the washing, the reaction vessel is located under the movement track of the transferring unit <NUM>, and is transferred to the outer circle 11d by the transferring unit <NUM> for measurement. When the reaction vessel is transferred under the rotation of the reaction tray to pass through the measuring apparatus <NUM>, the measuring apparatus <NUM> measures the signal in the reaction vessel. It should be noted that in other embodiments, the reaction vessel does not continue to be incubated after being transferred out of the incubation position while before passing into the B/F apparatus <NUM>, then the implemented total incubation time is t=t<NUM>=<NUM> minutes.

Those skilled in the art will appreciate that for the one-step delay and two-step protocol that requires two incubations, this embodiment can also implement the variability of each incubation time according to the incubation follows and method.

As can be seen from the above description, in the embodiment, the variable incubation time implemented by the incubation position is t<NUM>=(Ω/θ)T+C<NUM>, where Ω is the total forward angle of the reaction vessel in the incubation position with the rotating apparatus, Ω is an integral multiple of θ, and C<NUM> is a constant not greater than T. In particular, in the embodiment, in order to implement two or more incubation time, the total forward angle Ω of the reaction vessel in incubation position of the reaction tray with the rotating apparatus includes at least one value greater than <NUM>°, i.e.,, the variable incubation time t<NUM> includes at least one value greater than (<NUM> ° / θ) T. In this way, the reaction vessel can be carried forward by multiple rounds in the incubation position with the rotation of the reaction tray, so as to implement a flexible and variable incubation time. The disclosure can not only implement flexible and variable incubation time and make the control simple and efficient, but also simultaneously implement washing and/or measuring on the reaction incubation apparatus, such that the structure of the immunoassay analyzer is more simple, reliable, compact and the cost is lower, thereby effectively solving the problems in the prior art that in order to implement the variable incubation time, the control is complicated, the reliability is low, the high-speed automation is difficult to implement, and the washing and/or measuring cannot be implemented simultaneously.

Claim 1:
A reaction incubation apparatus (<NUM>), comprising:
a reaction unit (<NUM>) configured to carry and incubate a reaction vessel; and
a transferring unit (<NUM>) configured to transfer the reaction vessel into or out of the reaction unit (<NUM>);
wherein the reaction unit (<NUM>) comprises a rotating apparatus (<NUM>) provided with an incubation position, the incubation position is advanced by a predetermined angle θ at an interval of fixed time T with the rotating apparatus (<NUM>); the transferring unit (<NUM>) transfers the reaction vessel out of the incubation position according to a variable incubation time t<NUM>;
characterized in that the reaction incubation apparatus (<NUM>) further comprises a bound-free (B/F) apparatus (<NUM>), the rotating apparatus (<NUM>) is a reaction tray (<NUM>), the B/F apparatus (<NUM>) is disposed above the reaction tray (<NUM>), to directly wash and separate the reaction vessel on the reaction tray (<NUM>),
wherein the reaction tray (<NUM>) is rotatable about a central axis and is provided with four circles of reaction vessel positions (11a, 11b, 11c, 11d) centered on the center of rotation.