WO2018049926A1

WO2018049926A1 - Automatic liquid handling system

Info

Publication number: WO2018049926A1
Application number: PCT/CN2017/094485
Authority: WO
Inventors: 邵伟; 王栋
Original assignee: 清华大学
Priority date: 2016-09-19
Filing date: 2017-07-26
Publication date: 2018-03-22
Also published as: CN206096158U

Abstract

An automatic liquid handling system comprises a high-throughput liquid transferring device (1), a slide storage device (2), a temperature control device (3), a slide-transferring robotic arm (4), and a control device (5). The high-throughput liquid transferring device (1), the slide storage device (2), the temperature control device (3), and the slide-transferring robotic arm (4) are connected via data lines to the control device (5), respectively, and receive commands from the control device (5) to complete automatic handling of solutions. Each of the devices are integrated together by the slide-transferring robotic arm (4), realizing fully automatic handling of samples, and enhancing accuracy and reliability of experiments significantly.

Description

Automatic liquid handling system

Technical field

The present invention relates to an automated liquid handling system for biological experiments, and more particularly to an automated liquid handling system for simultaneous bulk storage, transfer and incubation of multiple sample liquids.

Background technique

With the development of science and technology, the innovation of experimental technology, experiments in the field of biochemistry, medical and other experiments involve more and more experimental equipment, and a large number of pipetting operations are required every day, such as mixing various liquid reagents and samples. Various volumes are accurately transferred to various analytical or test equipment for various preparation and testing. Taking magnetic particle extraction of plasmid DNA as an example, it involves not only the lysis of cultured bacteria, the binding of plasmid DNA to magnetic beads, the washing of heteroproteins, the elution of plasmid DNA, etc., but also the turbulence, magnetic frame placement. Adsorption, temperature incubation, etc.

The prior art pipetting device is usually a pipetting gun, generally a gun, a whole plate combination gun or a single gun manual operation mode, requires manual operation multiple times, and has a high risk of contamination between samples; oscillating, magnetic frame adsorption, temperature incubation Such operations generally require manual operation, and it is difficult to ensure the uniformity of processing between samples when multiple samples are present. The prior art pipetting device is automated, for example, Patent No. 200720071636.0 "An Automatic Pipetting Station", which provides an automatic pipetting device, which is completed by a plurality of sets of single-channel pipetting heads according to the entire row or the entire column. Plate operation; patent number 200820107586.1 "Automatic pipetting device", provides an automatic pipetting device, providing multi-channel pipetting head for 4-channel, 8-channel, 12-channel pipetting head, for 96 microporous plates, 384 micro Orifice pipetting efficiency is still low. At the same time, although this instrument integrates modules such as temperature control and oscillation, but because of its small flux and relatively fixed modules, it is relatively difficult to use for other experiments and has poor expandability.

Summary of the invention

In order to overcome the deficiencies of the prior art, the present invention provides an automatic liquid processing system, and the automatic liquid processing system of the present application can be placed in a large ultra-clean workbench or a clean workroom, Only high-volume samples can be accurately sampled, mixed, and sampled, and the device is also embedded with modules such as shock, temperature control, and magnetic frame. It can be fully automated for various biochemical experiments, and can be used according to the needs of the experiment. Integrate into more devices.

In one embodiment, an automatic liquid handling system is provided, the system comprising a high throughput pipetting device, a plate storage device, a temperature control device, a flapping robot arm, and a control device; a high throughput pipetting device, storage The plate device, the temperature control device and the rotating plate arm are respectively connected with the control device through a data line, and they cooperate with the automatic control of the liquid under the command of the control device.

In one embodiment, the high-throughput pipetting device includes a pipetting robot arm including a backing plate coupled to the top end of the body, a multi-channel pipetting device mounted to the lower portion of the pipetting robot arm, and a plate holder disposed within the body.

In one embodiment, the rack is provided with a storage platform on which a microplate, a sampling head box, an oscillator module, a waste tank module, and a magnetic frame module are placed.

In one embodiment, the multi-channel pipetting device includes a multi-channel pipetting head and a plate clamp.

In one embodiment, the multi-channel pipetting head utilizes a 96-channel or 384-channel pipetting head.

In one embodiment, the stocker rack includes a spindle, a shelf, and a base.

In one embodiment, the temperature control device includes a temperature controlled backing plate, a temperature control station, and a temperature controlled gasket.

In one embodiment, the temperature control device achieves temperature control by a water bath, an oil bath, or electric heating.

In one embodiment, the temperature controlled gasket comprises a gasket adapted to a non-flat bottom microplate or a gasket adapted to a flat bottom microplate.

In one embodiment, the flapper arm includes a vertical rail, four rotating robot arms, and a shifting plate clamp.

The invention has the following advantages in practical applications:

1. Small error, high accuracy and less cross contamination. The pipetting treatment in the present invention is completely completed by the system, which reduces the human error and greatly improves the stability and reliability of the pipetting. The use of disposable disposable sampling heads avoids cross-contamination between different liquids.

2. Fast and efficient. The invention integrates the rotating plate mechanical arm for the connection between the devices. Through optimization, multiple devices can work simultaneously according to the instructions, which greatly improves the work efficiency and the repeatability of the detection.

3. Wide applicability and good scalability. The devices of the present invention can be used not only separately. They can also be combined at will, and integrated into more devices according to experimental needs for a variety of experimental methods.

4. High throughput. The invention integrates the plate storage device, the sealing device, and the use of 96 or 384 microplates, can process tens of thousands of samples per day, and the experimental throughput is greatly improved, which is very suitable for large-scale sample processing, such as plasmid DNA extraction, PCR. System configuration, etc.

DRAWINGS

In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings to be used in the embodiments will be briefly described below. Obviously, the drawings in the following description are only some embodiments described in the present application. Other drawings may also be obtained from those of ordinary skill in the art in light of the inventive work.

Figure 1 is a schematic view showing the structure of an automatic liquid processing system of the present invention;

Figure 2 is a front elevational view of the high throughput pipetting device of the present invention;

Figure 3 is a side elevational view of the high throughput pipetting device of the present invention;

Figure 4 is a side elevational view of the multi-channel pipetting head of the present invention;

Figure 5 is a plan view of the shelf of the layer;

Figure 6 is a side view of the storage device;

Figure 7 is a schematic diagram of the temperature control device;

Figure 8 is a schematic view of a temperature controlled gasket;

Figure 9 is a schematic view of a rotating arm; and

Figure 10 is a plan view of the transfer arm.

detailed description

In order to make those skilled in the art better understand the technical solutions in the present application, the technical solutions in the embodiments of the present application will be clearly and completely described in the following with reference to the accompanying drawings in the embodiments of the present application. The embodiments are only a part of the embodiments of the present application, and not all of them. All other embodiments obtained by a person of ordinary skill in the art based on the embodiments of the present application without departing from the inventive scope should fall within the scope of the present application.

As shown in Figure 1, the structural block diagram of the automatic liquid processing system of the present invention includes five Parts: high-flux pipetting device 1, storage device 2, temperature control device 3, transfer arm 4, and control device 5.

As shown in FIG. 1, the high-flux pipetting device 1 comprises a backing plate 11, a pipetting robot arm 12 coupled to the top of the body, a multi-channel pipetting device 13 installed at the lower portion of the pipetting robot arm 12, and a plate frame provided in the body. 14. A storage platform is arranged in the plate frame 14, and various microporous plates, sampling head boxes, oscillator modules, waste liquid tank modules, magnetic frame modules and the like can be placed thereon for the convenience of experiments.

As shown in FIG. 2, FIG. 3 and FIG. 4, the multi-channel pipetting device 13 mounted on the bottom side of the pipetting robot arm 12 includes a multi-channel pipetting head 131 and a platen clamp 132, wherein: the multi-channel pipetting head 131 is selected. 96-channel or 384-channel pipetting head. The plate clamp 132 is connected to the pipetting robot arm bottom 12, and the three-dimensional movement of the XYZ axis can be performed on the plate frame 14 area to perform the consumable moving operation. The multi-channel pipetting head 131 is used for high-flux, same-range pipetting work; the rotating plate clamp 132 is matched with the rotating plate arm 4, and the sampling head box, reagent storage box, microplate, etc. required for the experiment are placed in the required state. Board or module, and moving out without consumables.

As shown in FIGS. 1, 5, and 6, the storage unit 2 includes a rotating shaft 21, a base 22, and a shelf 23. On the layer frame 23, the microporous plate, the sampling head box, the reagent tank and the like required for the experiment can be stored, and the layer frame 23 can be provided with multiple layers as needed. The rotating shaft 21 can be rotated by 0-360 degrees as needed to rotate the layer frame 23 to a position where the flapping robot 4 can be grasped. The shelf 23 is used for placing the consumables such as the sampling head box, the reagent storage box and the microplate, and is used for providing the sampling head box, the reagent storage box and the microplate required for the automatic operation; so that the multi-channel pipetting head 131 can The sampling head is mounted and unloaded at the plate position where the sampling head cartridge is placed; the liquid is transferred from or between the reagent storage box and the microplate. The use of the stocker device 2 corresponds to the expansion of the pallet 14 of the high-flux pipetting device 1, facilitating the operation of a large number of panels and the like.

As shown in FIG. 1, FIG. 7, and FIG. 8, the temperature control device 3 includes a temperature control back plate 31, a temperature control table 32, and a temperature control pad 33. The temperature control device 3 realizes temperature control by an external heat source such as a water bath, an oil bath or electric heating. The temperature-control spacer 33 shown in Fig. 8 is made of metal and has 16 rows and 24 rows of cone holes. The spacing and size of the vertebral body are completely matched with the standard 384V type plate. The temperature control device adopts the gasket of the non-flat bottom microplate or the gasket of the flat bottom microplate, compared with the conventional microporous plate and the thermostat direct contact method, the microporous plate hole, the plate The temperature difference is reduced and the temperature control uniformity is improved. Taking water bath temperature control as an example, the general working process of this equipment is temperature-controlled backboard. 31 and the temperature control table 31 are hollow, and externally heated water. The temperature is uniformed by the continuous circulation of warm water in the backing plate and the temperature control table. The temperature-controlled gasket 33 can wrap the 384-plate, and the metal conducts heat rapidly, so that the temperature difference between the plate and the plate of the 384-plate and the hole and the hole is small.

As shown in Figs. 1, 9, and 10, the flapper arm 4 includes a vertical rail 41, four

rotary robot arms

42, 43, 44 and 45, and a shifting plate clamp 46. The rotating robot arm 42 can move in the vertical axis Z axis, and is responsible for controlling the grasping height of the whole robot arm; the

rotating robot arms

42, 43, 44, 45 are sequentially associated with the built-in motor, can move XY axis, and the four rotating robot arms The greatly enhanced overall robotic arm's gripping flexibility allows it to be extended to any spatial position within the span. The shifting plate clamp 46 is attached to the rotating robot arm 45 to effect the grasping and placement of the consumables. The spanning range of the transfer robot 4 is a high-flux pipetting device 1, a plate storage device 2, and a temperature-control device 3; to take the consumables from the storage device 2, and place them in the high-flux pipetting device 1, for consumables After grabbing back to the original position as an example, the general workflow of the device is that the rotating arm 4 will be judged according to the program command, and then moved to the appropriate height along the slide rail 41, while the driving robot arm 42-45 is extended to the storage plate. The device 2, the shifting plate clamp 46 extends to grasp the consumables; then the driving mechanism arm is rotated, the rotating material is moved to the high-flux pipetting device, and the rotating plate clamp is released, and the rotating plate mechanical arm is returned to the initial state after the consumables are placed.

As shown in Fig. 1, the automatic liquid processing system of the present invention further includes a control device 5, which is generally a computer equipped with control software for an automatic liquid handling system. The back plate 11 of the high-flux pipetting device, the base 22 of the plate storage device, the base 33 of the temperature control device, and the vertical track 41 of the rotating plate arm are respectively connected to the control device 5 through a data line, and the control software can be sent through the data line. Control commands to various other parts of the system that allow the various parts of the system to operate in a predetermined manner to complete the predetermined experimental process.

The general workflow of the automatic liquid processing system of the present invention is to write an instrument control program according to the experimental procedure, and to tell the instrument all the actions (installing the sampling head, aspirating, draining, unloading sampling, etc.) and consumables types and specifications, placement position And place the required consumables on the rack. For example, to uniformly transfer the reagent tank liquid to four 384 microplates, a 384 sampling head cartridge is placed on the rack 14, the reagent tank to be dispensed, and the 384 microplate of the reagent are received. Under the control of the program, the pipetting robot arm 12 drives the multi-channel pipetting head 131 to move to the rack 14 on which the sampling head box is placed, and the pipetting head lowers the sampling head, and then the sampling head sucks the liquid from the reagent tank and discharges it to the purpose. 384 microplates, the gun head was unloaded after the program was completed. Can be placed on the shelf 14 The liquid tank, the oscillating module, the magnetic frame module, etc., realize the liquid waste collection, the shaking and mixing, the separation of specific components and the like.

It should be understood that the invention disclosed is not limited to the particular methods, aspects, and materials described, as these may vary. It is also understood that the terminology used herein is for the purpose of describing the particular embodiments of the invention, and is not intended to limit the scope of the invention.

Those skilled in the art will also recognize, or be able to ascertain, many equivalents of the specific embodiments of the invention described herein. These equivalents are also included in the appended claims.

Claims

An automatic liquid processing system, comprising: a high-flux pipetting device, a plate storage device, a temperature control device, a rotating plate arm, and a control device; a high-flux pipetting device, a storage device, a temperature control device, and a transfer The plate robot arms are respectively connected to the control device through data lines, and they cooperate with the automatic control of the liquid under the command of the control device.
The automatic liquid handling system according to claim 1 wherein said high-flux pipetting device comprises a multi-channel shift comprising a backing plate, a pipetting robot arm coupled to the top end of the body, and a lower portion of the pipetting arm. The liquid device, and the plate holder provided in the body.
The automatic liquid processing system according to claim 2, wherein a storage platform is disposed in the plate frame, and a microplate, a sampling head box, an oscillator module, a waste liquid tank module, and a magnetic force are placed thereon. Frame module.
The automatic liquid handling system of claim 2 wherein said multi-channel pipetting device comprises a multi-channel pipetting head and a platen clamp.
The automatic liquid handling system of claim 4 wherein said multi-channel pipetting head utilizes a 96-channel or 384-channel pipetting head.
The automatic liquid handling system of claim 1 wherein said shelf assembly includes a spindle, a shelf and a base.
The automatic liquid handling system of claim 1 wherein said temperature control device comprises a temperature controlled backing plate, a temperature control station and a temperature controlled gasket.
The automatic liquid processing system according to claim 7 wherein: The temperature control device realizes temperature control through a water bath, an oil bath or electric heating.
The automated liquid handling system of claim 7 wherein said temperature controlled gasket comprises a gasket adapted to a non-flat bottom microplate or a gasket adapted to a flat bottom microplate.
The automatic liquid handling system of claim 1 wherein said rotating robot arm comprises a vertical rail, four rotating robot arms and a shifting plate clamp.