JPH11271330A - Method for avoiding cross contamination between sample - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prevent contamination from occurring between the wells of a multi-well plate even if a sample solution, etc., is dropped at the time of moving nozzles, by providing relatively wide parts and relatively narrow parts between the lines or rows of the wells. SOLUTION: Nozzles are moved from a lower left home position along the lines of a multi-well plate in the direction of a broken line simultaneously with the start of operation, then are moved upward over a relatively wide interval part, and are halted beside a target row. Next, the nozzles are moved in a right direction, are halted above target wells to be operated, are vertically lowered to insert nozzle tips into the wells, and to discharge or suck a sample solution and a reaction reagent. After operation, a group of the nozzles is elevated above the wells, is returned in the reverse course to the home position, or is moved to other wells in the similar course. As each nozzle chip is not passed over the wells except the operated wells in the above-mentioned processes, cross contamination does not occur between the wells even if a liquid is dropped at the time of movement.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a multi-well plate used in the fields of biochemical research and clinical diagnosis, and a method for avoiding cross-contamination between wells such as a sample during a suction / discharge operation using the plate. It is.

[0002]

2. Description of the Related Art In the fields of biochemical research and clinical diagnosis, to reduce human costs and improve processing capacity,
Various automatic sample processing devices have been developed. For example, an apparatus using a multi-well plate such as a “96-hole plate” in which wells (recesses) are arranged in a pitch of 9 mm and a width of 8 rows × 12 columns is used. Each well of the multi-well plate is used as a sample container, a reaction container, a processed sample container, and the like.

[0003]

The multi-well plate has a large number of wells provided on a plate-like member. Usually, the size of the multi-well plate is reduced and the number of wells is reduced. The spacing between them is as narrow as possible. For this reason, when a liquid is discharged or sucked to an arbitrary well in a multi-well plate in which the arrangement of wells exceeds 3 rows × 3 columns, the nozzle tip used in the operation is such that the arbitrary well is Except in the case of being located in the outermost row or the outermost row, there is a problem that it always passes over the top of another well before and after the suction / discharge operation.

[0004] This problem is particularly encountered when using a multi-channel suction / discharge device in which a plurality of nozzles for mounting nozzle tips are provided so that suction and discharge operations can be performed on a plurality of wells by one operation. Notable.

An example will be described with reference to FIG. FIG.
Is a multi-well plate 1 in which 24 wells 2 are arranged in vertical 8 rows × horizontal 3 columns, and a total of 8 in vertical 8 rows × horizontal 1
The sample solution held in each well is sucked using a multi-channel suction / discharge device 3 equipped with the nozzles 4,
It shows a state of discharging to a well (not shown).

When a nozzle tip is mounted on the nozzle and the sample solution is sucked from the wells in the second row indicated by arrow 5 in the figure,
The nozzle tip inserted into the well A in the figure and touching the sample solution held therein is moved by the nozzle (nozzle shown in black in the figure) to which the nozzle tip is attached. If the sample solution does not pass through any upper part, it cannot move above the well to which the sample solution is to be discharged or cannot move to the home position (a position where the nozzle is retracted when the suction / discharge operation is not performed).

Here, a well A is provided inside the nozzle tip.
The sample solution held in the nozzle tip is sucked, and the sample solution is also attached to the outer periphery of the sample solution. There is a risk that the sample solution attached to the outer periphery or the tip of the nozzle tip may fall into another well and contaminate another sample solution held there. In recent years, high-sensitivity technologies such as chemiluminescence and polymerase chain reaction (PCR) have been used in the detection process in many cases. For example, a serious influence such as a false positive may occur.

For example, the sample in well A is strongly positive,
When the other sample is negative, when the sample solution of the well A attached to the nozzle tip falls into the shaded well, it should be determined to be negative due to contamination although it should originally be determined to be negative. The so-called false positive problem occurs.

[0009] Therefore, an object of the present invention is to provide a well even when a liquid such as a sample solution which is sucked into the nozzle tip or adheres to the outer periphery of the nozzle tip drops when the nozzle moves as described above. An object of the present invention is to provide a multi-well plate that does not cause contamination between the wells, and to provide a method of sucking and discharging a liquid such as a sample that does not cause contamination between wells by using the multi-well plate.

[0010]

According to the present invention, there is provided a multi-well plate having a plurality of wells, wherein a space between rows of wells or between columns of wells is relatively wide. A multi-well plate having a portion having a narrowed portion and a portion having a relatively narrow space between rows of wells or columns of wells.

[0011] The method of the present invention, which has been made to achieve the above object, is directed to a method of manufacturing a multi-well plate having a plurality of wells while avoiding contamination between wells by using a suction / discharge device equipped with a nozzle tip. A method of discharging a liquid to a well or sucking a liquid from an arbitrary well, wherein a portion between rows of the wells or columns between the wells is relatively wide, and a portion between rows or columns of the well is relatively narrow. Moving the nozzle tip to the top of any of the wells by passing the nozzle tip over a relatively large portion of the well or row of columns between the wells, where The method is characterized in that the nozzle tip does not pass over the top of any well other than the arbitrary well. Hereinafter, the present invention will be described in more detail.

The multi-well plate of the present invention can be made of a material that is stable with respect to biological samples such as blood and serum to be handled, and reagents added thereto, similarly to the conventional plate. The production method is not particularly limited, and a usual method such as mold molding or injection molding can be used.

The multi-well plate of the present invention has a portion where the space between rows or columns of wells is relatively wide, and a portion where the space between rows or columns of wells is relatively narrow. Having a relatively narrow portion between the rows or columns of the wells is a contrivance for placing more wells on a fixed size plate. The part where the space between rows or columns is relatively wide is
It is preferable to have a gap at least equal to the opening diameter of the well between the rows or columns of the wells, but in consideration of the number and arrangement of the nozzles provided in the dispensing device used in the suction and discharge operations. It can be determined appropriately. Here, one row of well means a series of wells arranged in the horizontal direction, and one row of wells means a series of wells arranged in the vertical direction. The vertical and horizontal directions of the plate are reversed depending on the angle at which the plate is viewed. For example, 8 rows x
A multi-well plate having 12 rows in the horizontal direction is synonymous with a multi-well plate having 12 rows in the vertical direction and 8 columns in the present specification.

When the multi-well plate of the present invention uses a multi-channel suction / discharge device having nozzles of 8 rows × 1 column as shown in FIG. 1, for example, two columns as shown in FIG. Of the wells as one group, the spacing between the well rows in each group is relatively narrow, while the spacing between the groups is at least as large as the opening diameter of the well or the separation distance of the center of the nozzle axis. Can be exemplified. If the device to be used uses a suction and discharge device having nozzles arranged in two or more horizontal rows, such as a multi-channel suction and discharge device having nozzles in eight rows and two horizontal columns, one column well is used. The wells and the nozzles are arranged in a zigzag manner as a group and as described later with reference to FIGS. 8 to 13, while a gap having a width equal to or larger than the amplitude width of the zigzag is arranged between the well rows. Can be exemplified.

As described above, the multi-well plate of the present invention is suitable for a processing operation by a suction / discharge device equipped with one or a plurality of nozzles.

The method of the present invention is a method for preventing contamination between wells by using the multi-well plate described above. That is, in the suction and discharge operations, the movement of the nozzle on which the nozzle tip is mounted is exclusively performed at the upper portion of the above-described portion where the space between rows or columns is widened. With the multi-well plate of the present invention according to the above-described configuration, by moving the nozzle above the wide gap, the upper part of the well other than any desired well is not moved. As a result, even if a liquid such as a sample that is sucked into the nozzle tip or adheres to the outer periphery of the nozzle tip due to vibration or impact during the movement of the nozzle drops, it only falls between the wells and contaminates other wells. I will not do it.

Regarding the moving direction and moving distance of the nozzle,
An appropriate program may be created based on the number of nozzles in the suction / discharge device, the size of the microwell plate, and the like, and may be executed by a movement control microchip in the device.

[0018]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, an embodiment of the present invention will be described in more detail with reference to embodiments shown in the drawings, but the present invention is not limited to this embodiment.

FIG. 2 shows an example of the multi-well plate of the present invention observed from above. The circular well portion holds a sample solution, a reaction solution, or a solution in which both are mixed. In this example, eight wells are arranged on a straight line, but one group is formed by a total of 16 wells of 8 rows × 2 columns. The width between adjacent groups is relatively wide, about the same as the width of each group (about 18 mm), but the distance between wells in each group is about 1/10 (1 m) of the well opening diameter (about 9 mm).
m) and the distance between the centers of adjacent well openings is about 9 mm. As described above, although the gap between the groups is wide, it is possible to reduce the size as a whole.

FIGS. 3 to 7 show a case where suction and discharge operations are performed on the multi-well plate shown in FIG. 2 using a multi-channel suction and discharge device having nozzles arranged in 8 rows and 1 column. (Indicated by a hatched circle in the figure). The nozzle is located at the home position (lower left in the figure) before starting the suction and discharge operations, and moves in the direction of the wavy line along the row of the multi-well plate with the start of the operation. The movement of the nozzle is controlled by a microchip (not shown) that stores the dimensions of the microwell plate, the gap between the rows of wells, and the like in advance.
The case where an operation is performed on individual wells is shown.

The nozzle groups are arranged in the first row and the second row from the left in the drawing.
A first group formed by a total of 16 wells in a row;
It moves upward in the figure through the upper part of the relatively wide gap portion disposed between the second group formed by a total of 16 wells in the row and the fourth row, and stops at the position in FIG. . At this time, since the nozzle group does not pass over any of the wells, a liquid is temporarily stored in the nozzle tip, and even if the liquid drops, it does not enter any of the wells.

Subsequently, the nozzle group moves rightward in the figure along the row of wells, and as shown in FIG. 5, a row of wells belonging to the second well group to be operated (left in the figure). From 3
Stop at the top of the eight wells located in the row (FIG. 5). At this position, the nozzle tip mounted vertically downward is inserted into the well, and a sample solution or a reaction reagent is discharged, or a sample already held in each well is sucked.

After the above suction and discharge operations are completed, the nozzle group rises to the upper part of the well, returns to the relatively wide gap, moves downward along the row of wells in the figure, and moves to the position shown in FIG. Stop. Thereafter, for example, it returns to the home position, or moves in the row direction of the well in order to discharge the sucked sample or the like to another well of the row as shown in FIG.

In the above steps, each nozzle chip does not pass over the upper part of the well other than the well for which suction and discharge operations have been performed using each nozzle chip. Therefore, even when vibration or impact occurs during the movement of the nozzle and the liquid drops from the nozzle tip, mutual contamination between the wells does not occur.

The case where the operation is performed on the third well row from the left in the drawing has been described above as an example. However, when the operation is performed on another row or by moving a single nozzle. When performing the operation, substantially the same effect can be achieved by controlling and moving the nozzle substantially in the same manner.

FIG. 8 shows another example of the multi-well plate according to the present invention, as viewed from above. In this example, 16 wells (opening diameter: about 11 mm) are arranged in a row in a zigzag manner, and 6 wells are arranged in a straight line in a row.
This is a multi-well plate having six rows. In each column, eight rows (eight in total) of zigzag wells are arranged symmetrically with respect to the line shown in FIG. 7 as surrounded by broken lines 6 in the figure.

Focusing on an arbitrary row of wells, the distance between the centers of the well openings is 9 mm (approximately 12.3 mm in linear distance) between adjacent wells in both the vertical and horizontal directions, and is relatively narrow. The distance between each row is relatively wide, 20 mm, which is almost equal to the amplitude (width of one row) of the zigzag-arranged rows.

FIGS. 9 to 13 show a multi-channel suction / discharge apparatus having a total of 9 nozzles arranged in 9 rows and 1 column (zigzag arrangement) with respect to the multiwell plate shown in FIG. The method of performing the suction and discharge operations is described mainly with respect to the movement of the nozzles (hatched circles and circles in the figure). Also in this example,
The nozzle group is controlled and moved essentially as described in FIGS. 3 to 7 (FIGS. 9 to 13).

As shown in FIG. 9, in the present embodiment, a total of eight wells surrounded by a broken line 6 in FIG.
While performing the discharging operation, each nozzle tip is prevented from passing through the upper part of the well except for the well for performing the suction and discharging operations. First, a nozzle tip carried on a nozzle tip holding means is mounted on each nozzle of a multi-channel suction / discharge device (8 in FIG. 9) having nine nozzles. Here, the nozzle chip holding means which is currently frequently used holds a total of 96 nozzle chips in 8 rows × 12 columns at a pitch of 9 mm both vertically and horizontally. Therefore, out of a total of 16 nozzle tips of 8 rows × 2 columns on the nozzle tip holding means, eight nozzles corresponding to the zigzag arrangement of wells are used.
9 are attached to eight nozzles other than the nine nozzles (indicated by ●). Next, among the 16 wells in an arbitrary row, FIG.
The suction and discharge operations are performed for eight wells located above the line 7 shown in FIG. 9 (FIGS. 9 to 13).

At the stage where the above operation has been completed, the eight nozzle tips left at the zigzag position of the nozzle tip holding means are mounted on eight nozzles other than the ten nozzles in FIG.
The suction and discharge operations are performed for the eight wells located below the line 7 shown in FIG. 8 in the figure (FIGS. 9 to 13).

As described above, by using a multi-well plate in which wells are arranged in a zigzag manner and a nozzle group arranged so as to correspond to the arrangement of the wells, commercially available nozzle tip holding means and the like which are currently frequently used are used. It is possible to avoid contamination between wells while realizing an efficient dispensing and discharging operation by using.

The case where one or two rows of wells are grouped has been specifically described above. However, other than these examples, when any nozzle in the nozzle group moves, the arbitrary nozzle is sucked. By arranging the wells so that two or more wells do not overlap on the movement path of the nozzle so as not to pass through the upper part of the wells other than the well for performing the discharging operation, it is possible to achieve the pollution avoiding effect of the present invention. is there. Pointed out, for example, in a zigzag arrangement, there is no limitation as long as an arbitrary nozzle in the nozzle group moves so that the arbitrary nozzle does not pass over the upper part of the well other than the well for performing the suction and discharge operations. Also, for example, the wells may be arranged so as not to overlap in the direction in which the nozzle is to be moved even in an arc-shaped arrangement not exceeding 1/2.

[0033]

The multi-well plate of the present invention avoids contamination between wells when a liquid such as a sample solution is suctioned and discharged to the wells using a suction and discharge device equipped with a nozzle tip. It is possible. Moreover, in order to manufacture it, a conventional manufacturing apparatus and materials can be used as they are. Cross-contamination between wells prevents serious problems such as false positives from occurring in current biochemical research where high-sensitivity measurements have become commonplace, and especially in clinical diagnosis using PCR. It is extremely important, and its significance is great.

The method of the present invention is a method of performing suction and discharge operations on wells while preventing mutual contamination between wells by using the multi-well plate of the present invention. Since the method is essentially how to control and move the nozzle portion of the device used for suctioning and discharging the liquid,
The configuration of the conventional device can be used as it is.
Therefore, the present invention can be carried out without discarding expensive devices that have been widely used so far, and the effect thereof is that serious problems such as false positives in high-sensitivity measurement are avoided by avoiding cross-contamination between wells as described above. That it can be prevented
This is extremely significant.

[Brief description of the drawings]

FIG. 1 is a diagram for explaining a problem of the related art.

FIG. 2 is a diagram showing an example of the multi-well plate of the present invention.

FIG. 3 is a diagram for explaining a method for avoiding cross-contamination between samples using the multi-well plate shown in FIG. 2;

FIG. 4 is a view for explaining a method for avoiding cross-contamination between samples using the multi-well plate shown in FIG. 2;

FIG. 5 is a view for explaining a method for avoiding cross-contamination between samples using the multi-well plate shown in FIG. 2;

6 is a diagram for explaining a method for avoiding cross-contamination between samples using the multi-well plate shown in FIG. 2;

FIG. 7 is a diagram for explaining a method for avoiding cross-contamination between samples using the multi-well plate shown in FIG. 2;

FIG. 8 is a diagram showing an example of the multi-well plate of the present invention.

9 is a diagram for explaining a method for avoiding cross-contamination between samples using the multi-well plate shown in FIG. 8;

FIG. 10 is a diagram for explaining a method for avoiding cross-contamination between samples using the multi-well plate shown in FIG. 8;

FIG. 11 is a view for explaining a method for avoiding cross-contamination between samples using the multi-well plate shown in FIG. 8;

12 is a diagram for explaining a method for avoiding cross-contamination between samples using the multi-well plate shown in FIG.

13 is a diagram for explaining a method for avoiding cross-contamination between samples using the multi-well plate shown in FIG. 8;

[Explanation of symbols]

 Reference Signs List 1 multi-well plate 2 well 3 multi-channel suction / discharge device 4 nozzle

Claims (2)

[Claims] 1. A multi-well plate having a plurality of wells, the portion having a relatively wide space between rows of wells or the columns of wells, and a relatively narrow space between the rows of wells or between the columns of wells. Multiwell plate. 2. A method of discharging liquid to or from a given well in a multi-well plate having a plurality of wells while avoiding contamination between wells by using a suction / discharge device equipped with a nozzle tip. Using a multi-well plate having a portion where the space between wells or rows of wells is relatively wide, and a portion where the space between wells or columns between wells is relatively narrow, the nozzle tip Moving to the top of any of the wells by passing the top of the well with a relatively wide portion between rows or columns, where the nozzle tip passes over the top of any well other than any of the wells The method characterized by not doing.