WO2014001829A1

WO2014001829A1 - Modular microfluidic disc

Info

Publication number: WO2014001829A1
Application number: PCT/HU2013/000061
Authority: WO
Inventors: Hunor SÁNTHA; Gábor HARSÁNYI; Máté VARGA
Original assignee: Bűdapesti Műskazi És Gazdaságtudományi Egyetem
Priority date: 2012-06-27
Filing date: 2013-06-26
Publication date: 2014-01-03
Also published as: HUP1200389A2; ZA201500244B; WO2014001829A8; IN2015DN00588A

Abstract

The invention relates to a microfluidic disc comprising components realised in a disc, that is, it comprises one (or more) space(s) receiving sample(s), one (or more) container(s) receiving reagent(s), one (or more) reaction space(s) as well as comprising channels connecting the proper components, where the location of the various components in relation to each other and their connection with the channels is such that it results in the blending of the sample(s) and the reagent(s) by a centrifugal force. The microfluidic disc comprises at least two parts, a base part (2) and a central part(l), where the central part (1) can be inserted into the base part (2), and in said central part (1) one or more containers (3a, 3b, 3c, 3d, 4a, 4b, 4c, 4d) receiving reagents are formed, where the proper container (3a, 3b, 3c, 3d, 4a, 4b, 4c, 4d) is connected with a proper outlet opening (10a, 10b, 10c,10d) at the periphery of the central part (1) by means of the a proper channel(s) (5) and at the edge of the inner region of the base part (2) joining the central part (1) one or more openings (6a, 6b, 6c, 6d) receiving sample(s) and one or more openings (7a, 7b, 7c, 7d) receiving reagent(s) are formed, where the proper opening(s) (6a, 6b, 6c, 6d) receiving sample(s) and the proper opening(s) (7a, 7b, 7c, 7d) receiving reagent(s) are connected with the proper reaction space (8a, 8b, 8c, 8d) by means of channel(s) (5).

Description

MODULAR MICROFLUIDIC DISC

The present invention relates to a microfluidic disc comprising components realized in a disc, that is, it comprises one (or more) space(s) receiving sample(s), one (or more) container(s) receiving reagent(s), one (or more) reaction space(s) as well as channels connecting the proper components, in a necessary case further comprising some valves regulating the flow of fluids as well as, in a necessary case, comprising one or more result readout space(s) where the location of the various components in relation to each other and their connection with the channels is such that it results in the blending of the sample(s) and the reagent(s) by a centrifugal force.

Diagnostic devices based on so-called lab-on-a-disc microfluidic systems are well-known in professional literature. In such systems the fluidic system is customarily carried by a plastic disc which is rotated by either a driver device compatible with the audio CD format or some other similar appliance and the centrifugal force generated thereby ensures the liquid flow of the proper direction and speed. Typically an optical readout unit performs the measurement of results from the blended liquids. In such centrifugal microfluidic systems samples can be separated, moved and blended relatively easily, by fine-tuning the centrifugal forces and the capillary forces arising from the properties of the material and the liquid sample. The valving is considered the most critical issue in microfluidic devices.

Passive versions of valves, can be formed relatively easy, in an integrated way, either by deploying hydrophobic valves, that is, through the spatially selective alteration of the surface hydrophobicity of the carrier base material along the microfluidic channel or with the help of capillary valves, that is, through the alteration of the diameters of the various sections of the channel, characteristically by narrowing or flattening the channel diameter.

A number of professional literature and patent publications deal with this subject. A microfluidic disc like this is introduced, for example in the lecture of Cho et al. entitled "Lab-on-a-disc for simultaneous analysis of blood chemistry and immunoassay" presented at the Twelfth International Conference on Miniaturized Systems for Chemistry and Life Sciences in October 2008 in San Diego, California, USA. In addition the international application for a patent under publication No. WO2011160015 is related to a similar microfluidic disc, also. In every known publication, the sample to be examined, e.g., blood is introduced into the disc with the help of a sample introducing tool, e.g., a micropipette, at the centre of the disc from where it is then launched towards the periphery of the disc by means of rotation, by centrifugal force, while the sample meets with the reagents. Such solutions have several disadvantages. In case the reagents placed in reagent containers are not in a lyophilized state (freeze-dried, in a flake state) they can blend to some extent in their vapours in the disc even before the test (since they must be filled in before sealing the packaging), which blending may generate unwanted contamination and can have a negative impact on the accuracy of the measurement.

Another disadvantage is the relatively complicated manufacturing technology related to disposable vapour blocking valves since in case of typical Point-of-Care and/or bedside-tests, the containers receiving the reagents have to be developed and filled up with the reagents in the disc and, during storage the permeability between the hollows has to be sealed down by valves. In practice this means that it is not possible or at least, not worthwhile to deploy liquid reagents in case of this type of device because only passive valves, which are not really vapour blocking, can be developed cost-effectively in lab-on-disc systems which can separate only materials in lyophilized state and even those only if the devices are not exposed to overly excessive shaking during storage.

The present invention is aimed at providing a solution that helps eliminating the above disadvantages.

The recognition which has led to the present invention is that the said

disadvantages can be eliminated if the disc has a removable central part and it is not the sample but the reagents that are placed at the centre of the disc, that is, into this central part and the sample is placed into the peripheral part of the disc .

Accordingly, the present invention, as described by the claims 1-12, relates to a microfluidic disc comprising components realized in a disc, that is, it comprises one (or more) space(s) receiving sample(s), one (or more) containers) receiving reagent(s), one (or more) reaction space(s) as well as channels connecting the proper components, in a necessary case, of some valves, preferably passive valves, regulating the flow of fluids as well as, in a necessary case, of one (or more) result readout space(s) where the location of the various components in relation to each other and their connection with the channels is such that it results in the blending of the sample(s) and the reagent(s) by a centrifugal force, where the disc comprises at least two parts, a base part and a central part, where the central part can be inserted into the base part, and in said central part one or more containers receiving reagents are formed, where the proper container is connected with a proper outlet opening at the periphery of the central part by means of the a proper channel(s) and at the inner region of the base part joining the central part one or more openings receiving sample(s) and one or more openings receiving reagent(s) are formed, where the proper opening(s) receiving sample(s) and the proper opening(s) receiving reagent(s) are connected with the proper reaction space by means of channel(s).

The base part preferably also contains a result readout space where the proper result readout space is connected to the proper reaction space.

In order for the central part to be inserted stably it is advisable that the central part is properly fitted into the base part, preferably with a tight enough fit.

In case of a preferred embodiment, in order for the central part and the base part to match well, a resilient intermediate piece is fixed onto the outer periphery of the central part, on which intermediate piece proper openings are formed for the liquid flow, that is at the location(s) joining to the outlet openings and receiving openings of the reagent(s). In another solution a flexible intermediate piece is fixed onto the inner region of the base part on which intermediate piece there are also proper openings formed for the flow of the liquids, that is, at the location(s) joining to the outlet openings and receiving openings of the reagent(s).

The said resilient, flexible intermediate piece is formed advisably of an elastomer.

The intermediate piece is preferably fixed to the central part or on the base part by mechanical pressing, sticking or bonding. Bonding may be for example plasma chamber bonding, ultrasonic or thermal bonding.

In case of another preferred embodiment the microfluidic disc has a positioning structure realized on the central part and the base part ensuring the proper fitting of the central part in the base part. There are countless possibilities for a positioning structure. However, one should strive for realizing the ones which are the simplest to carry out. Accordingly, positioning structure can, for example, be achieved by fabricating the central part and the hollow of the base part as rectangular shapes, or as irregular rectangular shapes, fitting to each other. A positioning structure can also be achieved by, for example, fabricating a square shaped central part with one cut down peak (vertex) and a square shaped hollow of the base part with one proper similar cut down at one of its comers (vertices), at the same location as at the central part.

In case of another preferred embodiment the central part containing the reagent(s) is sealed around with sealing packaging on its edges in its "stand-by" state before use, that is, in its position outside the base part; its openings are preferably sealed with film stripes in order for the central part to be transported safely and the reagents to be retained securely.

The present invention will be introduced in more detail through examples with the help of figures, where

Figure 1 is an axonometric view of the central part of a preferred embodiment of a microfluidic disc according to the invention

Figure 2 is an axonometric view of the base part of a preferred embodiment of a microfluidic disc according to the invention.

The central part 1 according to Figure 1 of the microfluidic disc according to the invention in its„stand-by" state before use that is, in its position outside the peripheral base part 2 has to be filled up with a reagent or reagents and then the central part 1 containing the reagents shall be sealed around on its edges with sealing packaging; in this case the openings of the central part 1 are sealed with film stripes that have to be removed before use, i.e., before insertion into the disc- shaped peripheral base part 2. Base part 2 in Figure 2 contains a hollow 11 for insertion of the central part 1. The central part 1 and, accordingly, hollow 11 are square shaped, as well, with properly positioned cut down vertices 13 and 14, respectively, on the similarly located comer-part of them for the proper positioning. In the middle of the central part 1 a rotating hole 12 is formed for centrifuging. Base part 2 contains openings 6a, 6b, 6c and 6d receiving samples, the openings 7a, 7b, 7c and 7d receiving reagents, the reaction spaces 8a, 8b, 8c and 8d, as well as result readout spaces 9a, 9b, 9c and 9d. In our example the central part 1 has a total of eight containers 3a, 3b, 3c, 3d, 4a, 4b, 4c and 4d receiving reagents of which each pair is connected by identical outlet openings 10a or 10b or 10c or 10d by means of channel(s) 5. Containers 3a, 3b, 3c, 3d receiving reagents contain identical reagents and likewise, containers 4a, 4b, 4c, 4d receiving reagents contain another identical reagent. In base part 2 there are a total of four openings 6a, 6b, 6c and 6d receiving samples, e.g., for four types of blood samples as well as four openings 7a, 7b, 7c and 7d receiving reagents, which openings are properly linked by means of channel(s) 5 as can be seen in Figure 2 and connected to reaction spaces 8a and 8b and 8c and 8d, respectively, from where the results can be read out from result readout spaces 9a and 9b and 9c and 9d, respectively, by means of an optical readout unit. Outlet openings 10a, 10b, 10c, 10d of the central part 1 overlap openings 7a, 7b, 7c, 7d of the base part 2 for receiving reagents when the central part 1 is inserted into the base part 2. A thin intermediate piece of elastomer not represented in the figure, the shape of which piece follows the periphery of the central part 1 , is placed onto the periphery of central part 1 by means of plasma chamber bonding, thermal or ultrasonic bonding. The a microfluidic disc according to the example contains capillary and hydrophobic valves, that is, passive valves known in themselves, regulating the liquid flow, the description of which does not belong to the invention.

After insertion of the materials of sample(s) to be examined and the central part 1 the microfluidic disc according to the example is placed on a rotating device with the help of hole 12, the liquid flow as a result of the centrifugal force will start.

In case of the known lab-on-a-disc solutions the sample is introduced from above with the help of some kind of sample introducing tools, e.g., a micropipette, to the central region of the disc, near the hole formed for the rotation from where it is launched towards the periphery of the disc as the rate of revolutions increase. In the solution according to the present invention the samples are not to be placed onto the central part but into the recess-like openings 6a, 6b, 6c and 6d receiving samples at hollow 11 of the base part 2. The packaging of the removable central part 1 will be unwrapped only when the sample is already introduced. This way the outlet openings 10a, 10b, 10c and 10d of containers 3a, 3b, 3c, 3d, 4a, 4b, 4c and 4d receiving reagents filled up in advance remain closed all along storage therefore not even the vapours of the reagents can blend or contaminate each other. The reagents of central part 1 placed onto its place subsequently, during usage start their way on the fluidic path from behind the sample. As the central part is a separate unit, the manufacturing technology of the disc containing the peripheral channel network becomes more simple because it is not necessary to realize the containers including the reagents in it, and to fill it up with reagents and, during storage, to seal down the transport pathway between the containers by means of valves.

An additional advantage arises from the fact that the reagents can join and be blended also from "behind" the sample and not only the sample can be trasported from the centre into the containers of the reagents as a result of centrifuging, as in case of the known lab-on-disc systems. Consequently, in this case any type of the analytical protocols can be adapted from the traditional micro-pipettor robot formulations to lab-on-disc platforms. The regulated alteration of the rate of revolution makes it possible to perform the necessary operations in a pre-planned order: e. g., to guide the sample to reach to the reaction space and after this, by increaseing the rate of revolution by one level the first reagent placed closer to the periphery breaks through its capillary valve and begins to get into the reaction space, then, increasing the rate of revolution by one level further the second reagent breaks through its capillary valve and begins to get into the reaction space. Finally, increasing the rotation speed by one additional level the entire compound of liquids (sample plus two reagents blended) get into the result readout space.

Another advantage is that only passive structures have to be formed on the disc. E.g., the proper openings can be formed by injection moulding. The sample, e.g., blood sample has to be touched to the brink of the opening(s) 6a, 6b, 6c and 6d receiving samples at the four edges of the square hollow 1 1 on the base part 2 and the capillary forces separate and absorb the proper volume.

There are several ways, in addition to the examples presented to realize the invention, within the scope of the protection, and therefore it cannot be considered as limited to the examples. It should be mentioned, for example, that, - needless to say - from among the many possibilities for different realization the disc according to the invention can be constructed for one single reagent and one single sample, as well as, for more than four samples and for more than two reagents and, in addition, a central part with a shape differing from a square or a rectangle is also possible, as a matter of course.

Claims

Claims:

1. A microfluidic disc comprising components realised in a disc, that is, it comprises one (or more) space(s) receiving sample(s), one (or more) container(s) receiving reagent(s), one (or more) reaction space(s) as well as channels connecting the proper components, where the location of the various components in relation to each other and their connection with the channels is such that it results in the blending of the sample(s) and the reagent(s) by a centrifugal force characterized in that the disc comprises at least two parts, a base part (2) and a central part(1 ), where the central part (1 ) can be inserted into the base part (2), and in said central part (1 ) one or more containers (3a, 3b, 3c, 3d, 4a, 4b, 4c, 4d) receiving reagents are formed, where the proper container (3a, 3b, 3c, 3d, 4a, 4b, 4c, 4d) is connected with a proper outlet opening (10a, 10b, 10c, 10d) at the periphery of the central part (1 ) by means of proper channel(s) (5) and at the inner region of the base part (2) joining the central part (1 ) one or more openings (6a, 6b, 6c, 6d) receiving sample(s) and one or more openings (7a, 7b, 7c, 7d) receiving reagent(s) are formed, where the proper opening(s) (6a, 6b, 6c, 6d) receiving sample(s) and the proper opening(s) (7a, 7b, 7c, 7d) receiving reagent(s) are connected with the proper reaction space (8a, 8b, 8c, 8d) by means of channel(s) (5).

2. The microfluidic disc according to claim 1 characterized in that the base part (2) contains a result readout space(s) (9a, 9b, 9c, 9d) where the proper result readout space(s) (9a, 9b, 9c, 9d) is connected to the proper reaction space(s) (8a, 8b, 8c, 8d).

3. The microfluidic disc according to claim 1 or 2 characterized in that it contains valves, preferably passive valves, regulating the liquid flow.

4. The microfluidic disc according to any of claims 1 - 3 characterized in that for a stable insertion of the central part ( ) the central part (1 ) is properly fitted in the base part (2), preferably with a tight fit.

5. The microfluidic disc according to any of claims 1 - 4 characterized in that a resilient intermediate piece is fixed onto the outer periphery of the central part (1 ), on said intermediate piece proper openings are formed for the liquid flow.

6. The microfluidic disc according to any of claims 1 - 5 characterized in that a resilient intermediate piece is fixed onto the inner region of the base part (2), on said intermediate piece proper openings are formed for the liquid flow.

7. The microfluidic disc according to claim 5 or 6 characterized in that the flexible intermediate piece is formed of elastomer.

8. The microfluidic disc according to claim 5 or 6 characterized in that the intermediate piece is fixed by mechanical pressing, sticking or bonding.

9. The microfluidic disc according to any of claims 1 - 8 characterized in that a positioning structure realised on the central part (1) and the base part (2) ensures the proper fitting of the central part (1 ) in the base part (2).

10. The microfluidic disc according to claim 9 characterized in that the positioning structure is achieved by realising the central part (1 ) and the hollow (11 ) of the base part (2) as rectangular shapes, or as irregular rectangular shapes.

1 1. The microfluidic disc according to claim 9 characterized in that the positioning structure is achieved by realising a square shaped central part (1 ) and a square shaped hollow (1 1 ) of the base part (2) both of them having a vertex cut down at the same locations.

12. The microfluidic disc according to any of claims 1 - 1 1 characterized in that the central part (1 ) containing the reagent(s) is fitted with sealing packaging in its „stand-by" state before use that is, in its position outside the base part (2) its openings are preferably sealed with film stripes.