WO2004099787A1

WO2004099787A1 - An automatic sample transport system and use thereof

Info

Publication number: WO2004099787A1
Application number: PCT/DK2004/000305
Authority: WO
Inventors: Rønsholt Per ANDRESEN
Original assignee: Visible Diagnostics A/S
Priority date: 2003-05-05
Filing date: 2004-05-04
Publication date: 2004-11-18

Abstract

An automatic sample transport system for feeding biological or non-biological samples to and from the analysis area of an analysis apparatus comprises a setup having three main areas formed by an analysis area (A), a sample taking area (B) and a sample storing area (C). The sample storing area (C) is preferably formed by four carousel magazines suspended in their respective sub-plates (6A, 6B, 6C, 6D), each of which is provided with a cut-out (7) through which a circularly movable sample taking unit (9) may move the individual samples via holders (13, 14) to the analysis area and back again by means of a needle (22) with a hook (23) and a pushing unit (8). The analysis area (A) includes a microscope with an objective (29) which analyzes the individual samples by means of image processing analyses. A very large number of samples may be examined automatically by the sample transport system according to the invention without any staff intervention. The sample transport system according to the invention is suitable for so called screening, e.g. examination for uterine cancer.

Description

An automatic sample transport system and use thereof

The invention relates to an automatic sample transport system, wherein a plurality of samples arranged in at least one magazine are taken out of the magazine individually by a sample taking unit and are passed to an analysis area in an analysis apparatus in which each sample is analyzed, and when the sample has been analyzed, the sample is returned to the magazine.

The invention moreover relates to a use.

Such sample transport systems, which are used in connection with automatic analysis of a large number of samples, are known in many different setups.

US Patent No. 4 761 075, e.g., discloses an automatic analysis system for analyzing cells by means of microscopy, where a plurality of samples are arranged in a plurality of cassettes, which are in turn arranged in a carousel. The samples are taken automatically from the individual magazines to the object table of the microscope and are returned to the cassette after completed analysis.

The number of samples that can be analyzed is rather limited in this known system, since the cassettes must be placed in a carousel which has a cer- tain limited capacity for receiving the cassettes.

Accordingly, an object of the invention is to provide an automatic sample transport system in which the number of samples which may be analyzed automatically without intervention from a laboratory technician is consider- ably larger than normal. The object of the invention is achieved by an automatic sample transport system of the type defined in the introductory portion of claim 1 , which is characterized in that the sample transport system has at least one magazine, preferably 2 - 4, and that the sample taking unit is formed by a mov- able unit having at least one holder which may be positioned in a plurality of positions.

Since the sample taking unit is movable, it is possible to move it to one or more magazines with samples, which may then contain a very large num- ber of samples in total. Thus, there are no actual limitations on the number of samples which may be analyzed in one analysis cycle, since the sample taking unit is not stationary, as it is in the setup according to the above- mentioned US Patent No. 4 761 075, but movable, which means that it may be adapted to many magazine configurations.

A good mechanical structure of the sample taking unit is achieved if, as stated in claim 2, the positions are distributed on a 360° circular area.

It is moreover expedient if, as stated in claim 3, the rotatable unit is posi- tionable at the analysis area of the analysis apparatus, since it is then relatively simple to transfer the sample to the object table of the analysis apparatus.

With a view to providing a reasonably compact sample transport system, it is advantageous if, as stated in claim 4, the system has three main areas, of which the first main area is an analysis area, the second main area is a sample taking area, while the third main area is a sample storing area.

To ensure a simple transfer of the samples themselves from the magazines to the analysis apparatus, it is an advantage if, as stated in claim 5, the rotatable unit is present in the main area and has movable parts which are adapted to extract the samples from the magazines in the main area and transport them to the analysis area in the main area and subsequently move them back from the analysis area to the rotatable unit and from there to the magazines.

A simple structure of the movable parts may be provided, as stated in claim 6, in that the movable parts comprise partly a needle with a hook adapted to be moved into the individual chambers of the magazines and take out samples from the magazines, and partly a pushing device adapted to push the samples back into the magazines.

This simple structure may be provided, as stated in claim 7, in that the gripper is formed by a wire with a bend having an acute angle, and, as stated in claim 8, in that the gripper needle is of an elastic material, preferably of metal or of a metal alloy, such as nitinol of the type having superelastic properties.

To ensure that many samples may be handled rapidly and simply by the sample transport system, it is an advantage if, as stated in claim 9, the samples are moved into a holder by a needle with a hook, while the samples are moved into the other holder by the pushing unit, and, as stated in claim 10, that the axes of rotation of the magazines are disposed in a horizontal plane.

With a view to reducing the risk that the samples are damaged during an analysis cycle, it is advantageous if, as stated in claim 11 , the rotatable unit comprises one or more detectors which are adapted to detect whether a sample, after having been moved to the rotatable unit from the magazine or from the analysis area to the rotatable unit, is positioned correctly, and to determine on the basis of this detection whether the movement of the rotatable unit is initiated. In normal operation as well as service and maintenance of the apparatus of the invention it is an advantage if, as stated in claim 12, the front plate is composed of four sub-plates, and that each sub-plate has a cut-out through which a sample may be taken out of the carousel.

With a view to avoiding mixing up the samples, it is advantageous if, as stated in claim 13, the movable unit may be positioned relative to a bar code reader which is adapted to identify the individual samples which are provided with a bar code.

The sample transport system is suitable for use in screening examinations if, as stated in claim 14, the analysis apparatus is formed by a microscope, preferably for the analysis of both biological and non-biological samples, and, as stated in claim 15, that the microscope is an automated microscope with automatic light intensity and with adjustment of its XYZ axes, as either the objective of the microscope itself may be adjusted, or its object table may be adjusted.

With a view to sorting samples or removing samples from the magazine, it is an advantage if, as stated in claim 16, an intermediate storage for samples is provided in a further cut-out in the front plate or the rear plate.

As mentioned, the invention also relates to a use. This use is defined in claim 17.

The invention will now be explained more fully with reference to the drawing, in which

fig. 1 shows an automatic sample transport system according to the invention, seen from the front, fig. 2 shows a section of the sample transport system of fig. 1 in a first operating position,

fig. 3 shows a second section of the sample transport system of fig. 1 in a second operating position, seen from the front,

fig. 4 shows a third section of the sample transport system of fig. 1 in a third operating position, seen from the front, while

fig. 5 shows a fourth section of the sample transport system of fig. 1 in a fourth operating position, seen from the front.

In fig. 1 , a sample transport system according to the invention, seen from the front, is designated 1.

As will be seen, it consists of a frame 6 in which four magazines 2, 3, 4 and 5 are positioned, said magazines protruding from the frame beyond the plane of the paper. This frame is composed of four sub-plates 6A, 6B, 6C, 6D which each have a cut-out, one of which being designated 7.

The individual samples, one of which being designated 10, may be moved through these cut-outs to and from the magazines, as will be explained more fully in connection with the other figures.

A rotatable sample taking unit 9 is arranged behind the frame 5, cf. figures

2 - 5, which inter alia show various parts of the sample transport system, which is adapted to take samples out of the magazine and move them back again, as will be explained later.

As will be seen from figures 2 - 5, the automatic sample transport system is formed by three main areas, designated A, B and C. The main area A is an analysis area, which, as the most important components, includes a microscope for the analysis of the individual samples as well as a carriage 16, 18 which is adapted to move the samples to and from an exact position below the objective of the microscope, which is designated 29 in fig. 3.

The second and central main area, designated B, is formed by a sample taking unit 9 which is adapted to move samples from the magazines 2, 3, 4, 5 to the analysis area A and back again.

The sample taking unit is driven by a motor 15 which imparts a circular movement to the sample taking unit 9.

As will additionally be seen, the sample taking unit has two holders 13, 14, which each consist of two plates between which brushes are arranged, which, however, cannot be seen in the figures. These holders are adapted for storing the samples temporarily during the transport from the magazines to the analysis area, and vice versa, cf. the following.

Finally, a sample storing area is designated C, formed by the four maga- zines 2, 3, 4, 5, which are configured as carousels of a type known per se, driven by their respective motors, one of which being designated 12 in the figures. The carousels are controlled such that, during a course of analysis, they are first adjusted to a reference position, following which they are moved in steps corresponding to the samples being successively moved out of the chambers of the carousels and back again.

It should also be noted that the individual samples in each magazine have their surfaces positioned in planes which are parallel with planes containing the axis of the magazines. The samples may be formed by a preparation, where cells, which may be embedded in an adhesive, are arranged between a slide and a cover glass. However, it is also possible to analyze other types of samples which may be biological or non-biological.

The microscope is connected with a calculating unit in the form of a colour analysis appliance which is capable of analyzing the samples on the basis of images taken by the microscope.

The analysis itself is not part of the present invention, but it should be mentioned, however, that the analysis may be provided by means of the combination of a focusing algorithm, as described in Danish Application No. PA 2003 01125, an image processing algorithm, as described in EP Patent No.

0917107, and a segmentation algorithm, as described in WO 02/075655.

It will now be explained how the automatic sample taking system according to the invention operates.

Fig. 2 shows a sample 10 just before it is to be taken out of the magazine and be transferred to the analysis area A.

As will be seen, a needle 22 with a hook 23 is moved inwards behind the sample in the chamber of the magazine. This needle may e.g. be of nitinol having superelastic properties and, at its one end, has a hook at an acute angle which constitutes a gripper utensil.

A pull at the needle 22 with a wire 24 moves the sample out of the maga- zine into the holder 13 at a position as shown at 10A, where the sample protrudes slightly from the holder 13. The sample taking unit is then rotated 180° to the position shown in figure 3, so that the sample with the holder 13 is arranged at the carriage 17, 18, which has a gripper part 16 capable of moving the sample from the position shown at 10A to the position shown at 10B, and from there, by means of the carriage 17, 18 movable in an X, Y direction as shown by the arrows 19, 20, to a correct position below the ob- jective 29 of the microscope. The part 17 may be moved in the directions of the arrow 20, while the parts 17, 18 may be moved in the directions of the arrows 19. The objective of the microscope may moreover be adjusted in the height.

When the analysis has been completed, the sample is to be returned to the magazine, which takes place in the following manner:

The sample taking unit 14 is rotated 180° so that the holder 14 with the brushes are arranged at the carriage 17, 18. The carriage 17 is then moved down toward the holder 14, where the sample is pushed into it. As will be seen, a pushing device is shown at the holder 14, consisting of a rod 17 which is provided with a solid pin at its free end. The opposite end of the rod is connected with a rotary shaft 20.

As will appear, the holder 44 is associated with the return of the sample by means of the pushing device, while the holder 13 is associated with the taking of the sample by the needle 22 and the hook 23.

As soon as the sample has been arranged in the holder 14, the sample taking unit is rotated by the motor back to the cut-out at the magazine, cf. fig. 5, following which the sample is pushed into the magazine by the pushing device, as shown in dashed line in fig. 5. The sample taking device is then rotated back to the position shown in fig. 2, at the same time as the magazine has moved the next sample to the cut-out 7, and the process may be repeated, as explained above.

When all analyses in a first magazine have been completed, the procedure is repeated for the other magazines, as the movable unit is then just posi- tioned at the next cut-outs belonging to the respective magazines. It should moreover be noted that it is also possible to move the sample through another cut-out to an intermediate storage, as will be explained briefly later.

A typical course of analysis may be summarized as follows:

At the beginning of an analysis, the magazines with samples are positioned at their respective front plates.

The rotatable unit is moved to one of the cut-outs at one of the magazines, following which the needle 22, 23 is moved into the magazine and pulls the sample out of it, with simultaneous reading of a bar code on the sample e.g. via a bar code reader arranged on the front plate.

The sample is moved from the rotatable unit into the microscope where the actual analysis takes place.

After completed analysis, the sample is moved back to the rotatable unit, and the sample is moved back to the magazine via the pushing mechanism 28 on the rotatable unit.

Then, a further sample is taken out, said magazine being rotated first so that the position of the next sample will be at one of the cut-outs in a front sub-plate.

When all samples in the first magazine have been analyzed, the rotatable unit is moved to a cut-out at another magazine, and so on.

It should moreover be noted that the sample transport system may also be used for the sorting of the samples according to the following model: If it is desired to transfer a sample to another position, e.g. in another magazine, the sample, after having been taken out of a magazine, may be moved through a cut-out in the front plate to an intermediate storage, where it may be stored until the space intended for it is free, following which the sample may be moved to this space. This facility may also be used for storing samples which are perhaps damaged or unfit for analysis.

Finally, it is noted that the sample transport system contains several detectors, some of which are adapted to detect whether the samples are posi- tioned correctly in the various areas of the analysis apparatus, and if so to stop the apparatus such that, e.g., it is ensured that the samples are not squeezed and perhaps get damaged.

Other detectors may detect whether magazines are arranged in the front sub-plates, and whether samples are arranged in the individual magazines.

Detectors may also be arranged to record a reference point in order to synchronize the analysis apparatus.

Claims

PATENT CLAIMS

1. An automatic sample transport system, wherein a plurality of samples arranged in at least one magazine (2, 3, 4, 5) are taken out of the magazine individually via a sample taking unit (9) and are passed to an analysis area (A) in an analysis apparatus, in which each sample is analyzed, and when the sample has been analyzed, the sample is returned to the magazine, characterized in that the sample transport system has at least one magazine, preferably 2-4, and that the sample taking unit is formed by a movable unit having at least one holder (13,14) which may be positioned in a plurality of positions.

2. A system according to claim ^characterized in that the positions are distributed on a 360° circular area.

3. A system according to claim^' 1 or 2, ch a ra cte rized in that the rotatable unit (9) is positionable at the analysis area of the analysis apparatus.

4. A system according to claims 1 -3, ch a ra cterized in that the system has three main areas (A, B, C), of which the first main area (A) is an analysis area, the second main area (B) is a sample taking area, while the third main area (C) is a sample storing area.

5. A system according to claims 1 -4, cha ra cterized in that the rotatable unit is present in the main area (B) and has movable parts which are adapted to extract the samples from the magazines in the main area (C) and transport them to the analysis area in the main area (A) and subsequently move them back from the analysis area to the rotatable unit and from there to the magazines.

6. A system according to claim 5, characterized in that the movable parts comprise partly a needle (22) with a hook (23) adapted to be moved into the individual chambers of the magazines and take out samples from the magazines, and partly a pushing device (27, 28) adapted to push the samples back into the magazines.

7. A system according to claim 6, characterized in that the gripper is formed by a wire with a bend having an acute angle.

8. A system according to claim 7, characterized in that the gripper needle is of an elastic material, preferably of metal or of a metal alloy, such as nitinol of the type having superelastic properties.

9. A system according to claims 6-8, ch a racte rized in that the samples are moved into the holder (13) by the needle (22) with the hook

(23), while the samples are moved into the other holder (14) by the pushing unit.

10. A system according to claims 1 -9, characterized in that the axes of rotation of the magazines are disposed in a horizontal plane.

11. A system according to claims 1 -10, characterized in that the rotatable unit comprises one or more sections which are adapted to detect whether a sample, after having been moved to the rotatable unit from the magazine or from the analysis area to the rotatable unit, is positioned correctly, and to determine on the basis of this detection whether the movement of the rotatable unit is initiated.

12. A system according to claim 10, c h a ra cte ri ze d in that the magazines are provided in a frame (5) formed by four sub-plates, and that each sub-plate has a cut-out through which a sample may be taken out of the carousels.

13. A system according to claims 1 -12, characterized in that the movable unit may be positioned relative to a bar code reader which is adapted to identify the individual samples which are provided with a bar code.

14. A system according to claims 1 -13, characterized in that the analysis apparatus is formed by a microscope, preferably for the analysis of both biological and non-biological samples.

15. A system according to claim 14, characterized in that the microscope is an automated microscope with automatic light intensity and with adjustment of its XYZ axes, as either the objective of the microscope itself may be adjusted, or its object table may be adjusted.

16. A system according to claims 1 -15, characterized in that an intermediate storage for samples is provided in an additional cut-out in the front plate or the rear plate.

17. Use of a system according to claims 1 - 16 for the screening and/or diagnosis of uterine cancer.