A control method for reducing the residual amount of liquid discharged from a biochip reactor

Abstract

The present invention provides a method for controlling the amount of residual liquid discharged after dumping of a biochip reactor, the method comprising the following steps: a first step, adding a liquid with a density less than the reaction reagent to a reactor with or without a reaction reagent; a second step, after the reaction is completed, driving the biochip to rotate, and the reagent and liquid in the reactor flow out under the action of gravity. The present invention adds a liquid with a density less than the reagent and does not react with the reagent to the reagent surface of the reactor, and the liquid continuously replenishes the gap between the reagent and the reactor wall during dumping, reduces the surface binding energy of the reagent and the reactor, plays a lubricating and driving role, and makes the residual reagent in the reactor after dumping to be at the microliter level, and the dumped reagent can participate in subsequent reactions without introducing cross contamination, and the operation method is flexible and simple.

Description

Technical Field

[0001] The invention belongs to the field of biochips, and in particular relates to a control method for reducing the residual amount of dumped liquid discharged from a biochip reactor. Background Art

[0002] Biochips are currently mainly used in in vitro diagnostic products, such as specific biochips made for the diagnosis, treatment, and prevention of specific diseases. Driven by the demand for new coronavirus detection, biochip technology has developed rapidly. In the automated operation of existing chips, the transfer flow of multiple reagents or the discharge of waste liquid is generally achieved by positive or negative pressure drive, centrifugal force drive, external pressure component drive, or the use of siphon principle combined with special channel design. The structural design and operation of the above methods are generally complicated. By integrating the reactor into the chip and dumping the reactor to discharge liquid, it has the advantage of simple operation. Combined with special design, it can reduce the amount of liquid residue after dumping.

[0003] Chinese patent application No. 201811034640.9 discloses a biochip reactor dumping and drainage structure, in which a hydrophobic material is coated on the inner wall of the reactor, and a water-absorbing material is arranged on the outside of the reactor cup mouth, so that the residual amount of reagent in the reactor after dumping is reduced to a microliter level. However, the addition of a hydrophobic coating to the reactor may contaminate the reagent, and the external water-absorbing material absorbs the liquid, which is not suitable for the need for reaction after liquid transfer.

[0004] Chinese patent application No. 201110401674.9 discloses an instrument for processing samples in droplets and a method for using the same. The method places a hydrophobic medium in a liquid reservoir, tilts the device and discharges the hydrophobic medium, leaving the hydrophobic medium at the bottom of the device, and then adds a rinse solution that is insoluble in the hydrophobic medium and miscible with the droplets, thereby fixing the droplets and performing biological or chemical treatment on the droplets, which is beneficial for providing a biocompatible surface and reducing evaporation; however, after pouring, the bottom of the droplets contains the hydrophobic medium, which is not suitable for the subsequent droplets to continue to react with other reagents, and there is cross contamination. Summary of the invention

[0005] The purpose of the present invention is to provide a method for controlling the amount of residual liquid discharged after dumping of a biochip reactor, so as to solve the technical problems that reagents can participate in subsequent reactions after the reactor is dumped, and to reduce the amount of residual reagents in the reactor after dumping.

[0006] In order to solve the above technical problems, the specific technical solutions of the present invention are as follows:

[0007] A method for reducing the residual amount of liquid discharged from a biochip reactor, the method comprising the following steps:

[0008] The first step is to add a liquid with a density lower than that of the reaction reagent into a reactor that already has the reaction reagent or does not have the reaction reagent;

[0009] In the second step, after the reaction is completed, the biochip is driven to rotate, and the reaction reagents and liquid in the reactor flow out under the action of gravity.

[0010] Therefore, the present invention adds a liquid with a density smaller than that of the reagent and which does not react with the reagent and the chip material to the reagent surface, and selects a suitable pouring angle and residence time through program control, so that the residual reagent in the reactor after pouring is at a microliter level, accounting for less than 5% of the original volume, and the poured reagent can participate in subsequent reactions without introducing cross contamination.

[0011] Furthermore, the biochip includes a chip base and a reactor, the chip base is provided with an installation cavity for accommodating the reactor, and the reactor is suspended and installed in the installation cavity; a receiving container is provided on one side of the reactor; and the opening of the receiving container corresponds to the liquid outlet of the reactor.

[0012] Furthermore, the biochip is mounted on a tray rack, and a rotating assembly for driving the chip base to rotate is provided on the tray rack; by arranging a receiving container on one side of the reactor, the rotating assembly drives the chip base mounted on the tray rack to rotate, thereby pouring the reagents in the reactor into the receiving container, and the reagents after pouring can participate in subsequent reactions.

[0013] Furthermore, the rotating assembly includes a motor shaft, a motor and a control panel, the motor shaft is connected to the tray rack, and the control panel controls the motor to drive the motor shaft to rotate; the control panel can set the tilting angle and residence time of the biochip.

[0014] Furthermore, the outer wall surface of the reactor is suspended on the wall surface of the installation cavity by a rotating part, and the rotating part is a slot arranged in the installation cavity and a rotating shaft arranged on the outer wall of the reactor and connected to the slot; in this way, the entire reactor forms a swinging motion mode when shaking, so that the reagents in the reactor achieve a more ideal mixing effect.

[0015] Furthermore, the reactor and the receiving container are both made of transparent polymer materials; the transparent polymer materials such as polycarbonate (PC), polypropylene (PP) or polymethyl methacrylate (PMMA) are integrally formed.

[0016] Furthermore, the liquid is an oily liquid; the oily liquid is one or more of silicone oil and paraffin oil; the density of silicone oil or paraffin oil is smaller than that of the reagent and will not react with the reagent and the chip material.

[0017] In addition, when the chip base rotates, it rotates 140°-150° with the central axis of the tray rack toward the side of the receiving container where the biochip is set. Preferably, the pouring angle is 143°. When the pouring angle of the biochip is 143°, the edge of the liquid outlet on the pouring side of the reactor is at a right angle to the horizontal plane, and the most liquid is poured out; the chip base stays for 2-4s after rotating to the set angle, and preferably the tilting residence time is 3s; the program controls the pouring angle and residence time to ensure that after pouring, the residual reagent in the reactor is as little as possible, and after pouring, it can smoothly enter the receiving reactor to participate in subsequent reactions.

[0018] The method for controlling the amount of residual liquid discharged after dumping of a biochip reactor of the present invention has the following advantages: an oily liquid having a density smaller than that of the reagent and not reacting with the reagent is added to the reagent surface, and the oil continuously replenishes the gap between water and the reactor wall at the moment of dumping, thereby reducing the surface binding energy between the reagent and the reactor and playing a lubricating and promoting role; at the same time, through the design of appropriate dumping angle and residence time parameters, the residual reagent in the reactor after dumping is at a microliter level, accounting for less than 5% of the original volume, thereby reducing reagent waste, and the dumped reagent can participate in subsequent reactions without introducing cross contamination, and the operation method is flexible and simple. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 It is a schematic diagram of the structure of the biochip of the present invention;

[0020] Figure 2 It is a schematic diagram of the structure of the biochip installed on the tray rack;

[0021] Figure 3 Dump state diagram for biochip;

[0022] Explanation of the markings in the figure: 1. Chip base; 2. Mounting cavity; 3. Card slot; 4. Reactor; 5. Rotating shaft; 6. Adapter; 7. Motor shaft; 8. Tray rack. DETAILED DESCRIPTION

[0023] In order to better understand the purpose, structure and function of the present invention, the present invention is further described in detail below in conjunction with the accompanying drawings.

[0024] like Figure 1 and Figure 2As shown, the biochip used in the present invention includes a chip base 1, a reactor and a receiving container 6; the chip base 1 is provided with a mounting cavity 2 for accommodating the reactor, the reactor is suspended and mounted in the mounting cavity 2, and the outer wall of the reactor is suspended and mounted on the wall of the mounting cavity 2 through a rotating member, the rotating member is two slots 3 arranged in the mounting cavity 2 and two rotating shafts 5 arranged on the outer wall of the reactor and connected to the slots 3, and the rotating shafts 5 are coaxial. A receiving container 6 is arranged on one side of the reactor; the opening of the receiving container 6 corresponds to the liquid outlet of the reactor, so that the reagent in the reactor can be poured into the receiving container 6;

[0025] The chip base 1 can be installed on a tray rack 8, and a rotating component for driving the chip base 1 to rotate is provided on the tray rack 8; the rotating component includes a motor shaft 7, a motor and a control panel, the motor shaft 7 is connected to the tray rack 8, and the control panel controls the motor to drive the motor shaft 7 to rotate.

[0026] As one embodiment of the present invention, the reactor is a cup body with a reaction pool 4; as another embodiment of the present invention, the reactor is a "U"-shaped tube; the "U"-shaped tube structure can add reaction reagents from the right side of the tube, and the reagents stay at the bottom of the "U"-shaped tube after addition, and then add oily liquid to the left side of the "U"-shaped tube; after the biochip is poured to the right, the oily liquid plays a lubricating and driving role, reducing the amount of reagent residue in the "U"-shaped tube after pouring, and the reagents can participate in subsequent reactions after pouring.

[0027] In order to facilitate observation of the reaction of the liquid in the cup, the reactor and the receiving container 6 are both made of transparent polymer materials. At the same time, in order to achieve the purpose of light weight and reduce the wall thickness of the cup body, the cup body is integrally formed of polypropylene material, polycarbonate material or polymethyl methacrylate material. The cup body of this embodiment adopts a lightweight design, and the product wall thickness is relatively thin, so that the transparency of the cup body is improved, which is convenient for identifying lighter-colored reagents, thereby expanding the scope of use.

[0028] When the present invention is used, it comprises the following steps:

[0029] The first step is to add an oily liquid with a density lower than that of the reagent to a reactor that already has a reaction reagent or does not have a reaction reagent. The oily liquid is one or more of silicone oil and paraffin oil, and does not react with the reagent and the chip material.

[0030] The second step is to start the rotating assembly after setting a suitable pouring angle and residence time on the control panel after the reaction is completed. The motor shaft of the rotating assembly drives the tray rack 8 to rotate, and the reagents and oily liquid in the reactor flow into the receiving container 6 under the action of gravity. The pouring angle of the chip base is 140°-150° rotated from the central axis of the tray rack, and the pouring angle is preferably 143°; the tilting residence time of the chip base is 2-4s after rotating to the set pouring angle, and the tilting residence time is preferably 3s; after the 3s tilting residence time, the rotating biochip returns to a horizontal state, and the residual reagent in the reactor is at a microliter level at this time, and the residual reagent volume accounts for less than 5% of the original volume. After the reagent flows into the receiving container 6, it mixes and reacts with the reagent in the receiving reactor. Due to its low density, the oily liquid always floats on the surface of the reagent and does not pollute the reagent.

[0031] Example: The present invention can reduce the residual amount of reagents in the reactor after the chip is dumped, improve the reagent utilization rate, and the current residual reagent volume is less than 10ul, accounting for less than 5% of the original volume. The following data are 80 groups of random continuous test data during the test. Test conditions: 200ul of eluent reagent is added to the reactor 4, and 50ul of silicone oil is added to the surface, and then dumped to quantitatively test the residual reagent volume.

[0032]

[0033]

[0034] It is to be understood that the present invention is described by some embodiments, and it is known to those skilled in the art that various changes or equivalent substitutions may be made to these features and embodiments without departing from the spirit and scope of the present invention. In addition, under the teachings of the present invention, these features and embodiments may be modified to adapt to specific circumstances and materials without departing from the spirit and scope of the present invention. Therefore, the present invention is not limited by the specific embodiments disclosed herein, and all embodiments falling within the scope of the claims of this application are within the scope of protection of the present invention.

Claims

1. A method for reducing the residual amount of liquid discharged from a biochip reactor, characterized in that: The biochip comprises a chip base, a reactor and a receiving container; a mounting cavity for accommodating the reactor is provided in the chip base, the reactor is suspended and installed in the mounting cavity, the outer wall surface of the reactor is suspended and installed on the wall surface of the mounting cavity through a rotating member, the rotating member is two slots arranged in the mounting cavity and two rotating shafts arranged on the outer wall of the reactor and connected to the slots, and the rotating shafts have a coaxial centerline; a receiving container is arranged on one side of the reactor; the opening of the receiving container corresponds to the liquid outlet of the reactor, so that the reagent in the reactor is poured into the receiving container; the chip base is installed on a tray rack, and a rotating component for driving the chip base to rotate is provided on the tray rack; the rotating component comprises a motor shaft, a motor and a control panel, the motor shaft is connected to the tray rack, and the control panel controls the motor to drive the motor shaft to rotate; When using, the following steps are included: The first step is to add an oily liquid with a density lower than that of the reaction reagent to a reactor that already has a reaction reagent or does not have a reaction reagent; the oily liquid is one or more of silicone oil and paraffin oil, and does not react with the reagent and the chip; In the second step, after the reaction is completed, the biochip is driven to rotate, and the reaction reagents and liquid in the reactor flow out under the action of gravity.

2. The method for reducing the amount of residual liquid discharged from a biochip reactor according to claim 1, characterized in that: A receiving container is arranged at one side of the reactor; the opening of the receiving container corresponds to the liquid outlet of the reactor, and the reactor and the receiving container are both made of transparent polymer materials.

3. The method for reducing the amount of residual liquid discharged from a biochip reactor according to claim 1, characterized in that: The biochip is mounted on a tray rack, which is provided with a rotating assembly for driving the biochip to rotate. When the biochip rotates, it rotates 140°-150° toward a side of a receiving container along the central axis of the tray rack; the biochip stays for 2-4 seconds after rotating to a set angle.

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