FR2524874A1 - Serological etc. analysis of liq. sample - by transfer between reagent cells via capillaries in multicell bar pivoted on centrifuge plate - Google Patents

Abstract

The reagents are in separate cells in a container in the form of a short, straight bar. The cells are arranged in longitudinal succession, linked by capillary passages to each other and to a liq. sample reception chamber at one end of the bar. Centrifugal force on the bar is employed to transfer the sample liq. from the reception chamber to the first cell, from the first to the second and so on. To obtain this centrifugal force, the bar is fixed on to a horizontal rotary plate. Alternate transfers of the liq. are made after pivoting the bar about a vertical axis passing through a radius of the rotary plate. Each time the bar is pivoted, the direction of rotation of the plate is pref. reversed. The effect is to apply centrifugal force first to one long side of the bar and next to the opposite long side. The system is for laboratory analysis of micro-litre samples of liq. by contact with reagents which are further processed, e.g. by photocolorimetric analysis. Specific applications include serological and immunoenzymological analyses. The appts. is simple and inexpensive and speeds up the work as carried out at present.

Description

Method and device for transferring low liquid doses
The invention relates to a method and a device for the transfer of low liquid doses contained in at least one receptacle, carried by a packaging material in the form of a bar, to cells also carried by said material for the partial filling of said cells, communication means comprising capillary conduits being provided between the receptacle and the cells, the bar being arranged on a rotating plate and the transfer, comprising several phases, being carried out by application of the centrifugal force resulting from the rotation of the plate.

 A delicate problem in the transfer of very low doses of liquid samples, for example of a few microliters, results from the use of capillary conduits connecting the receptacle to the different cells.

 The use of centrifugal force, which results in an increase in the apparent density, makes it possible to overcome the capillary forces of retention.

 The invention aims to improve the operation of devices of the type described above.

 It relates to a method of transferring a small quantity contained in at least one receptacle, carried by a packaging material in the form of a bar, to cells also carried by said material for the partial filling of said cells, means of communication comprising capillary conduits being provided between the receptacle and the cells, the bar being disposed on a turntable and the transfer, comprising several phases, being produced by application of the centrifugal force resulting from the rotation of the tray, characterized in that between the different phases of the transfer, the bar is made to pivot on the plate so as to apply centrifugal force to one and the other of the longer sides of the bar.

 It also relates to a device for the implementation of this method and which is characterized by the fact that it comprises means ensuring the pivoting of the bar on the plate around a point located in the vicinity of the periphery of the plate .

 Other characteristics and advantages of the invention will emerge from the description which follows and from the appended drawing relating to several examples of implementation of the invention.

 FIGS. 1A and 1B schematically represent the two positions that a packaging bar can adopt on a turntable, in accordance with the invention.

FIGS. 2A to 2K relate to an example of implementation of the method according to the invention. %
FIGS. 3A to 3L relate to a second example of implementation of the method according to the invention.

 FIGS. 11A to 4G relate to a third example of implementation of the method according to the invention.

 In FIGS. 1A and 1b, the reference 1 designates a turntable (only half has been shown) and the reference 2 a packaging material in the form of a bar comprising at least one receptacle and cells, calibrated or not, means of communication , comparing capillary conduits, being provided between the receptacle and the cells.

 Firstly, before the application of the method according to the invention, the bar 2 can be arranged radially, as shown in dotted lines in FIG. 1A, for a phase of loading the receptacle using a sample suitable liquid.

 Then the bar is arranged according to one of the two positions referenced a in FIG. 1A, b in FIG. 1B, these positions being symmetrical with respect to a radius of the plate.

 The plate is provided with suitable means allowing on the one hand the maintenance of the bar 2 in one and the other position and on the other hand the pivoting from one position to the other.

 When the bar is placed in position a and the plate 1 rotates in direction A, the centrifugal force is applied to the side 4 of the bar 2, substantially perpendicular to this side, according to arrow E; on the other hand when the bar is placed in position B and the plate 1 rotates in the direction B the centrifugal force is applied to the opposite side 5 of the bar 2, substantially perpendicular to this side according to arrow F.

 By way of illustration and in no way limitative, the plate 1 can have a diameter of the order of 20 to 22 cm, the bar 2 can have a length of the order of 6 to 7 cm for a width of 1 to 2 cm.

 FIGS. 2A to 2K relate to an example of implementation of the method according to the invention in which a liquid sample is brought successively into contact with several reagents arranged in separate cells, before being subjected to an analysis, for example photocolorimetric; for reasons of simplification, the bars have simply been shown, either in position a or in position b.

 The bar 20 has a receptacle 21 for the liquid sample 20 'communicating with a calibrated chamber 22. The liquid coming from this chamber 22 can be directed either to an overflow chamber 23 or to a cell 24 containing an appropriate reagent represented by reference 25.

 The strip includes a plurality of cells such as 24 containing suitable reagents communicating with each other, the last cell 26 containing the reagent opening into a cell 28 preceding the analysis cell 29. The means of communication between the different compartments of the strip have orifices and / or capillary conduits in a manner known per se. Furthermore, the different compartments have suitable curved profiles facilitating the passage from one compartment to another.

 The bar 20 being disposed on the turntable in position b, the liquid sample 20 'having been introduced into the receptacle 21, the tray is rotated in the direction B.

 The liquid sample 20 ′ passes into the calibrated cell 22 which it gradually fills (FIG. 2B) for completely, the excess liquid passing into the overflow chamber 23 (FIG. 2C).

 This principle of delivering a determined dose has in particular been described in French patent application No. 81 07437 filed on April 14, 1981 by the Applicant.

 After this first phase, the bar is placed in position a and the plate is rotated in direction A.

 The liquid contained in the calibrated cell 22 passes into the first cell 24 containing the reagent 25 (Figures 2D and 2E), then the bar is placed in position b and the plate is rotated in direction B.

 The liquid contained in cell 24 then passes into the next cell (Figures 2F, 2G).

 After each transfer from one cell to another, the position of the bar on the plate is changed.

 In FIG. 2H, the bar is shown in position b, the liquid sample being in cell 26 where it is brought into contact with the reagent 27.

 The bar is then placed in position b on the plate and by rotation in direction B the liquid is transferred into cells 28 then 29 (Figures 21, 2J, 2K) where lton performs an analysis, for example photocolorimetric.

 The volume of the calibrated cell 21 is less than the volumes of the cells containing the reagents so that the filling of these cells is only partial, the liquid thus being able to be agitated when it is present in said cells.

 FIGS. 3A to 3L relate to an example of implementation of the method according to the invention in the field of immunoenzymological analysis.

 A solid attachment support is generally used, which may consist of a spherical polystyrene ball coated with a protein having properties of the anti-body type. This support is placed in a container in which the compound containing the substance to be analyzed is admitted. After an appropriate incubation time, remove excess compound and vigorously wash the ball with water.

A first reagent is then introduced, the excess of which is then eliminated.

After washing, a second reagent is introduced before carrying out a photocolorimetric analysis.

 The bar 30 has a first receptacle 31 situated at a first end of the bar into which a washing liquid, for example water, can be introduced, which communicates with an analysis cell 36 situated at the other end of the bar through a channel 38.

 In the analysis cell 36, there is a hooking support 37 constituted by one or more suitable balls. The analysis cell 36 has an orifice 39 forming a weir for ejecting the washing liquid.

 The compound containing the substance to be analyzed is introduced into a receptacle 31 'contiguous to the receptacle 31. The receptacle 31' communicates with a calibrated chamber 32. The liquid coming from this chamber 32 can be directed either to an overflow chamber 33, or towards cell 36 using channel 38.

 Appropriate reagents are trapped in cells 34 and 35 and can be released from these cells by suitable means not shown.

 The means of communication between the different compartments of the bar include orifices and / or capillary conduits in a manner known per se. Furthermore, the different compartments have suitable curved profiles facilitating the passage from one compartment to another.

 After introduction of the liquid compound 30 'containing the substance to be analyzed into the receptacle 31', the bar 30 being positioned on the turntable in position b, the plate is rotated in the direction B.

 The compound 30 ′ passes into the calibrated cell 32 which it gradually fills (FIG. 3B) then completely, the excess passing into the overflow chamber 33 (FIG. 3C).

 After this first phase, the bar is placed in position a and the plate is rotated in direction A.

 The liquid contained in the calibrated cell 32 passes into the analysis cell 36 via the channel 38 and comes into contact with the attachment support 37. The capacity of the calibrated cell 32 being lower than that of the cell 36, and the rotation being carried out in direction A, the compound 30 ′ cannot escape from cell 36 (Figures 3D, 3E, 3F).

 After an appropriate incubation time, the bar is placed in position b and the plate is rotated in direction B so as to expel the excess liquid through the orifice 39 (Figures 3G and 3H). A washing is then carried out by introducing water into the receptacle 31 and by rotating the plate in the direction A, after having placed the bar in position a (FIG. 3I).

 The water remaining in cell 36 is then removed by placing the bar in position b and rotating the plate in direction B (Figure 3J).

 After this operation, the bar is replaced in position a and the reagent 34 ′ contained in cell 34 is released by appropriate means. The plate is rotated in direction A under the effect of centrifugal force, reagent 34 'is driven to the analysis cell, from which it cannot escape, the volume of reagent 34' being less than the volume of cell 36 (Figure 3K, 3L).

 After this operation, the excess reagent is removed, washed with water and the second reagent 35 ′ contained in cell 35 is introduced. To carry out this sequence of operations, the maneuvers explained with reference to FIGS. 3G are repeated, 3H, 31, 3J, 3K and 3L.

 The solid attachment support can also consist of at least part of the walls of the analysis cell.

 FIGS. 4A to 4G relate to an example of implementation of the method according to the invention in the field of serological analysis from a liquid sample, multiple analyzes are carried out. This involves injecting into cells containing appropriate reagents calibrated doses of liquid, these doses only partially filling said cells.

 A packaging device, in the form of a bar, allows such multiple analyzes has been described in French patent application No. 82 00529 filed on January 14, 1982 by the Applicant.

 This device comprises a receptacle in connection with n calibrated analysis cells into which analysis reagents are introduced, the liquid to be analyzed being conveyed from the receptacle to said analysis cells by centrifugation, each of the cells being provided with an orifice capillary for introducing liquid and a capillary air exhaust duct. The device is in the form of a bar, a first end of which comprises said receptacle, the latter opening into a first tank, or precook, communicating on the one hand with the first analysis cell through the capillary orifice for introducing the liquid and on the other hand with a second precuvette, which communicates on the one hand with the second analysis cell through the capillary orifice liquid introduction and on the other hand with a third precuvette, and so on, the nth precuvette, which is in communication with the (n-1) th precuvial, communicating with the nth analysis cell by the o capillary port for introducing liquid and an overflow cell located near the second end of the bar, the volumes of the precuvettes being slightly greater than the volumes of the analysis cells with which they are respectively seated, the analysis cells , as well as the precooks1 being substantially aligned along the bar, the means of communication between the precooks being arranged so as to allow successive filling of these and not simultaneous, said conditioning device being able to be fixed on a circular plate rotating, along a radius of said plate, the end of the bar comprising the receptacle being situated towards the center of the plate, the end comprising the overflow chamber being situated towards the periphery of the plate.

 The bar 40 has a receptacle 41 into which the liquid sample 40 'is introduced. The receptacle 41 opens into a first pre-cell 42 communicating on the one hand with the first analysis cell 42 'containing the appropriate reagent 42 "and on the other hand with a second pre-cell and so on; the last pre-cell referenced 49 communicates with the analysis cell 49 ′ containing the reagent h ″ and an overflow cell 50.

 After introduction of the sample 40 ′ into the receptacle 41, the bar 40 is placed on the turntable in position a and the tray is rotated in the direction A.

 The sample 40 ′ is expelled from the receptacle 41 towards the precuvettes which it fills one after the other, the excess being directed towards the overflow chamber 53 (FIGS. 11A to 4E), then the bar is put in the position b and the plate is rotated in direction B. The liquid contained in the pre-tanks is then expelled to the analysis cells where it comes into contact with the reagents previously placed in these cells (4F, 4G).

 Of course, the invention is in no way limited to the embodiments described and shown, which have been given only by way of examples. In particular, it is possible, without departing from the scope of the invention, to make detailed modifications, to change certain provisions or to replace certain means by equivalent means.

Claims (5)

1 / Method for transferring a small quantity of liquid contained in at least one receptacle, carried by packaging material (2) in the form of a bar, to cells also carried by said material for the partial filling of said cells, communication means comprising capillary conduits being provided between the receptacle and the cells, the bar (2) being arranged on a turntable (1) and the transfer, comprising several phases, being carried out by application of the centrifugal force resulting from the rotation of the plate, characterized in that between the different phases of the transfer, the bar is pivoted on the plate so as to apply centrifugal force on one and the other of the longest sides (4, 5) of the bar (2). 2 / A method according to claim 1, characterized in that the two extreme positions (a, b) of the bar (2) on the plate (1) are symmetrical with respect to a radius of the plate. 3 / A method according to claim 2, characterized in that the centrifugal force is applied substantially perpendicular to the longest edges (4, 5) of the bar (2). 4 / Method according to one of claims 1 to 3, characterized in that one alternates the direction of rotation of the plate after each transfer phase. 5 / Device for the transfer of a liquid in small quantity contained in at least one receptacle carried by a packaging material (2) in the form of a bar towards cells also carried by said material, means of communication, comprising capillary conduits , being provided between the receptacle and the cells, the bar (2) being arranged on a rotating plate (1) and the transfer comprising several phases being carried out by application of the centrifugal force resulting from the rotation of the plate (1), characterized by the fact that it comprises means ensuring the pivoting of the bar on the plate around a point located in the vicinity of the periphery of the plate (1).