Abstract:
An apparatus for performing bioanalytic processing and analysis, a bioanalytical reaction device, and a cartridge thereof are provided. The cartridge contains a housing and at least one sample chamber in a platform for storing biological samples, which the bioanalytical reaction device can process and analyze. The platform is movably connected to the housing such that the platform is movable between a stowed position, in which the sample chamber is protected by the housing, and an extended position, in which the sample chamber is outside of the housing. The bioanalytical reaction device includes an actuation device for moving the platform between the stowed and extended positions.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of International Application Ser. No. PCT/CH2010/000095 filed Apr. 9, 2010, now pending, which claims the benefit under 35 U.S.C. §119(a) of European Patent Application No. EP09157972, filed Apr. 15, 2009, the entire contents of both of which are incorporated herein by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     This invention relates to apparatus for performing bioanalytic processing and analysis. In particular, the present invention relates to a bioanalytical reaction device and a cartridge thereof. The cartridge contains at least one sample chamber for storing biological samples, the bioanalytical reaction device can process and analyze. 
     2. Description of Related Art 
     One example of a bioanalytical reaction is the DNA polymerase chain reaction. The polymerase chain reaction (PCR) is a technique that permits amplification and detection of nucleic acid sequences. This technique has a wide variety of applications including DNA sequence analysis, detection of genetic mutations, diagnoses of viral infections, to name but a few. With the PCR a specific target sequence or strand of DNA can exponentially amplificated. The polymerase chain reaction comprises repeated cycles of target denaturation by heating the sample, primer annealing at a lower temperature and polymerase-mediated extension at a slight higher temperature. At the last step, the DNA polymerase synthesizes a new DNA strand complementary to the DNA template strand. Under optimal conditions, the amount of DNA target strands is doubled. 
     Besides to PCR, other bioanalytical reactions are known, for example the ligase chain reaction. More generally, several import bioanalytical methods are dependent upon changing the temperature of samples in a controlled fashion. Therefore, there is a need for the automation of these methods. 
     Several mechanical and automated bioanalytical reaction devices are known in the art. Certain devices use cartridges for storing biological samples, so that the one or more biological samples in one cartridge can be temporarily stored, while the biological samples in another cartridge can be processed in the bioanalytical reaction device. An operator only needs to remove the one cartridge from the device and insert the other cartridge into the device. 
     Such cartridges have various interfaces, such as one or more interfaces for heating a sample in the cartridge as well as one or more interfaces for optical reading out the result of the reaction, which is, for example, indicated by a certain color of the sample or by certain illuminating substances. 
     More specifically, the samples to be processed are stored in one or more chambers in the cartridge. In general, an interface is provided by a wall of one of the chambers through which the sample can be heated or analyzed. If an optical readout has to be performed, the chamber needs a transparent wall as interface. 
     SUMMARY OF THE INVENTION 
     It may be a problem, that such interfaces can be damaged or become dirty. Especially, when an operator handles such a cartridge, there is the possibility that he touches the cartridge at a location of an interface. An interface in the form of a thin wall can already be damaged by the force applied by a finger. Also, sweat or grease can be deposited on the interface in this way. A damaged or dirty interface can result in leakage from the cartridge or falsification of the optical detection. 
     It is an object of the invention to provide a safe and simple cartridge. 
     According to an exemplary embodiment of the invention, a cartridge for a bioanalytical reaction device is provided, the cartridge comprising at least one sample chamber for a sample, the at least one sample chamber having a wall through which the sample can be processed or analyzed by the bioanalytical reaction device, wherein the cartridge comprises a housing and a platform, the platform comprising the at least one sample chamber, wherein the platform is movably connected to the housing, such that the platform is movable between a stowed position, in which the wall is protected by the housing, and an extended position, in which the wall is outside of the housing. 
     Such a cartridge is protected from becoming damaged or polluted without unnecessarily complicating the structural design of the cartridge and the bioanalytical reaction device. 
     It is to be understood that herein the term “cartridge” is used for every kind of device capable of being connected with a bioanalytical reaction device. For example, a cartridge may be a holder, magazine, cassette or carrier. 
     The at least one sample chamber is placed on a platform (or disc or carrier) that can be extended from the cartridge. In the stowed position, the sample chamber is inside the housing of the cartridge. Consequently, the chamber is protected from getting damaged or dirty. For use, the platform is extended from the cartridge, e. g. for enabling it to interface with heaters and optical sensors of a bioanalytical reaction device. 
     The wall of the at least one sample camber can be a heating interface or, if the wall is translucent (at least for some wavelength), an optical interface for interfacing with components of the bioanalytical reaction device, such as a heater or an optical sensor. 
     According to a further exemplary embodiment, a cartridge is provided, wherein the at least one sample chamber is connected to a channel for filling the at least one sample chamber, the channel ending in the vicinity of the actuation means. 
     Vicinity may be understood as relating to a length of one of the following intervals: 0 to 15 millimeters (mm), 0 to 10 mm, and 0 to 5 mm. 
     The at least one sample chamber is connected to a channel for filling and draining the at least one sample chamber with fluids, such as the solution in which the sample is dissolved. Instead of a channel, every means adapted to conduct a fluid from one point to another, such as a line, a pipe or a hose, can be used. One end of the channel can be connected to a line of the bioanalytical reaction device, which can pump fluids over the line into the sample chamber. The end of the channel is part a fluidal interface of the cartridge. 
     Placing the end of the channel in the vicinity of the actuation means has the advantage that a mechanical connection for moving the platform and a fluidal connection can be integrated in one component of the cartridge. 
     According to a further exemplary embodiment, a cartridge is provided, wherein a part of the channel is located within the actuation means. The channel may be located in a shaft for rotating the platform or in a spindle for moving the platform. This is one possibility of integrating the mechanical and the fluidal connection of the cartridge. Further the at least one sample chamber may be filled independent of the position of the platform. 
     According to a further exemplary embodiment, a cartridge is provided, wherein the wall is arranged at a first side of the platform, wherein the platform has a second side opposite to the first side, and wherein the platform in the extended position is accessible from the first side and the second side by the bioanalytical reaction device for processing or analyzing the sample. The sample within the at least sample chamber may be processed or analyzed simultaneously from two sides of the platform. 
     According to a further exemplary embodiment, a cartridge is provided, wherein at least one dimension of the cartridge with the platform in the extended position is bigger than this dimension of the cartridge with the platform in the stowed position. Therefore, the cartridge with the platform in the stowed position can easily be stored. 
     According to a further exemplary embodiment, a cartridge is provided, wherein the platform is rotatably connected to the housing. Preferably, the actuation means is a shaft and the platform is connected to the shaft for rotating the platform about a rotation axis. More preferably, the shaft extends up to an opening in the housing. In this way, the mechanical connection of an actuator of the bioanalytical reaction device to the cartridge for rotating the platform can easily be established. Further, the opening in the housing may provide a guidance for the shaft, and therefore for the platform. 
     Alternatively, according to a further exemplary embodiment, a cartridge is provided, wherein the platform is slidably connected to the housing. The actuation means may be a spindle for translatorily moving the platform from the stowed position to the extended position. 
     According to a further exemplary embodiment, a cartridge is provided, wherein the platform has the form of a plate, which, in the stowed position, is arranged between a first wall and a second wall of the housing. A platform in the form of a plate, i. e. a component with one dimension much smaller than the two other dimensions in different directions, can be provided with more than one sample chamber and all of the sample chambers are easily accessible by a bioanalytical reaction device. 
     According to a further exemplary embodiment, a cartridge is provided, wherein the wall of the at least one sample chamber is thin. For minimizing the thermal barrier, the wall may be thin and can for example be a foil with a high heat conductance. Herein, with a thin wall a wall is meant which has a thickness of about less than 200 micrometers (μm). A thin wall may also optimize the transparence of the optical interface of the at least one sample chamber. 
     According to a further exemplary embodiment, a cartridge is provided, wherein the at least one sample chamber is formed by an opening in the platform which is covered by a foil or thin layer forming the thin wall. 
     Another aspect of the invention is a bioanalytical reaction device having a slot or receptacle for receiving the cartridge, comprising an actuator for extending and stowing the platform of the cartridge. The actuator may be a step motor. 
     According to a further exemplary embodiment, a bioanalytical reaction device is provided, having a reservoir for filling the at least one sample chamber, wherein the reservoir is connectable with the at least one sample chamber over a line ending in a mechanical connection of the actuator with the actuation means for moving the platform. Within the mechanical connection, there also may be the fluidal connection of the bioanalytical reaction device with the cartridge. The fluidal interface or fluidal connection of the bioanalytical reaction device and the mechanical connection are integrated in one component. 
     According to a further exemplary embodiment, a bioanalytical reaction device is provided having a cartridge presence sensor for detecting the presence and/or the correct insertion of the cartridge in the slot. Only when a cartridge is present in the slot, the bioanalytical reaction device should operate the line for filling the sample chamber. Otherwise, fluids can polute the interior of the bioanalytical reaction device. 
     According to a further exemplary embodiment, a bioanalytical reaction device is provided, which is adapted to effect the actuator to move the platform in the extended position, when the cartridge presence sensor detects the presence of the cartridge in the slot. 
     These and other aspects of the invention will be apparent from and elucidated with reference to the embodiment described hereinafter. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Below, an embodiment of the present invention is described in more detail with reference to the attached drawings. It shows: 
         FIG. 1  shows a perspective view of a cartridge for a bioanalytical reaction device with a platform in the stowed position. 
         FIG. 2  shows a perspective view of the cartridge of  FIG. 1  with the platform in an extended position. 
         FIG. 3  shows a schematic cross sectional view of parts of the platform of  FIG. 2 . 
         FIG. 4  is a schematic topview on the platform of  FIG. 2 . 
         FIG. 5  shows a schematical diagram of functional components of a bioanalytical reaction device. 
     
    
    
     DETAILED DESCRIPTION OF EMBODIMENTS 
       FIG. 1  shows a perspective view of a cartridge  10  for a bioanalytical reaction device. The cartridge  10  has a housing  12  with an upper cover or wall  14  and a lower cover or wall  16 . It is to be understood that the wording “upper” and “lower” are used for reasons of simplicity and are not intended to be limiting. For example, the cartridge  10  may be inserted into a bioanalytical reaction device not in the shown orientation but in an upstanding orientation. 
       FIG. 1  shows the platform  30  in a stowed position. The platform  30  is rotatably connected with the housing  12  via a shaft  32  as actuation means. The shaft  32  is guided by the opening  33  in the upper cover  14 . By rotating the shaft  32  about the rotation axis A the platform  30  can be extended from the housing  12  of the cartridge  10 . 
       FIG. 2  shows a perspective view of the cartridge  10  with the platform  30  in an extended position. The platform  30  has exited the housing  12  through a slit  18  in the housing  12  between the upper cover  14  and the lower cover  16 . By a further rotation of the shaft  32  in the opposite direction around the rotation axis A, the platform  30  can again be stowed in the housing  12 . In the stowed position the platform  30  is protected from being damaged or getting dirty. In the extended position the platform  30  can be accessed by actuators like a heater or a sensor of a bioanalytical reaction device. 
     Further, in  FIG. 2  it can be seen that the platform  30  comprises five sample chambers  34 . 
       FIG. 3  shows a schematic cross-sectional view of parts of the platform  30 . In particular, the left-hand side of the drawing shows a cross-sectional view of a sample chamber  34 , the right-hand side of the drawing shows a cross-sectional view of the vicinity of the rotation axis A. 
     Platform  30  comprises a plate  38  that may be made of plastics. For each sample chamber  34  there is an opening  36  in the plate  38 . On one first side of the plate  38 , a first or upper foil  40  is applied. For example, the upper foil  40  may be glued to the plate  38 . In the shown embodiment, the upper foil  40  has a thickness of about 100 μm. In the region of the opening  36  the upper foil  40  forms a thin wall of the sample chamber, the thin wall being a heating interface  44  of the sample chamber  34 . If a heating or cooling source is arranged outside of the sample chamber  34  in the region of the heating interface  44  heat may be transferred to the interior of the sample chamber  34  or may exit it. 
     On the other second side of the plate  38 , opposite to the first side, there is applied a second or lower foil  42  of a translucent material. The lower foil  42  may be glued or in some other way be connected to the plate  38 . Also, the lower foil  42  has a thickness of about 100 μm. In the region of the opening  36 , the lower foil  42  forms an optical interface  46  of the sample chamber  34 . In this region, light can penetrate the translucent lower foil  42 . Light coming from the interior of the sample chamber can be detected by an optical sensor arranged near the optical interface  46  of the sample chamber  34 . 
     Further,  FIG. 3  shows a first channel  48  formed by a groove or notch in the surface of the plate  38  and covered by the upper foil  40 . In the same way a second channel  50  is formed connecting the sample chamber  34  with a third channel  52  within the shaft  32 . 
     It is to be understood, that there are other possibilities to form the sample chamber  34  and the channels  48 ,  50 ,  52  within the platform  30 . For example, the platform  30  may be manufactured from two parts being mirror symmetric and having openings and grooves which form the sample chambers and the channels, when the two parts are connected with each other. Further, it would be possible, to provide the plate  30  with pits. With a foil or thin layer covering the pits sample chambers can be formed on the plate. In this case, such sample chambers would have only one interface. 
     From  FIG. 4  being a schematic top view on the platform  30 , it can be seen, that the sample chambers  34  are fluidly connected via channels  48 ,  50  with channels  52  formed in the shaft  32  in the vicinity of the rotation axis A. Over the channels  48  and  50  each sample chamber  34  can be filled with solutions, e.g. a solution containing DNA fragments to be analyzed or amplified. Also, the sample chambers  34  can be emptied by conducting a gas, e.g. air, or other solutions or liquids like water through the channels  48 ,  50  into the sample chamber  34 . 
     The shaft  32  with the channels  52  is a fluidal interface  54  of the platform  30 . 
     Since the fluidal interface  54  is in the vicinity of the rotation axis A, it can be accessed over the mechanical connection of the bioanalytical reaction device for rotating the platform  30 . Therefore, the mechanical connection and the fluidic connection are combined and the number of connections between the cartridge  10  and a bioanalytical reaction device is reduced. 
       FIG. 5  shows a schematical diagram of a bioanalytical reaction device  60 . The bioanalytical reaction device  60  has a slot  62  for receiving the cartridge  10 . With an actuator  64 , for example a step motor, which is rotatably connected with the shaft  32  the platform  30  can be extended from the cartridge  10  to an extended position and be returned in a stowed position.  FIG. 5  shows the platform  30  in an extended position. The fluid lines  70  are connected with inlets and outlets combined with the mechanical connection  66 . The inlets and outlets fit to their respective counterparts formed in the shaft  32 . A pump and reservoir mechanism  68  can fill the sample chambers  34  in the platform  30 . The bioanalytical reaction device has one or more heaters  72  for heating the samples within the sample chambers  34  from the first side of the platform  30  and one or more optical sensors  74  for analyzing the light emitted from the interior of the sample chambers  34  from the second side of the platform  30 . 
     Over a controller  76  which is connected over control lines  78  with the actuator  64 , the pump and reservoir mechanism  68 , the heater  72  and the optical sensor  74 , the bioanalytical reaction device  60  can control the analysis and processing of the samples in the sample chambers in an automated way. For example, the bioanalytical reaction device  60  can conduct the above mentioned PCR procedure. 
     Further, it is possible, that the bioanalytical reaction device  60  controls the extension and the stowing of the platform  30  in an automated way. When an operator inserts the cartridge  10  into the slot  62 , a mechanical sensor  80  detects the presence of the cartridge  10 . Alternatively, the detection can be done with an optical sensor. With this input the controller  76  directs the actuator  64  to rotate the platform  30  in the extended position. After that, several processings, like filling the chambers with different solutions, heating the sample chambers  34  and analyzing the light from the sample chambers  34 , can be performed by the controller  76 . When the processing and the analysis is done, the controller  76  directs the actuator  64  to rotate the platform  30  back to the stowed position and an operator can remove the cartridge  10  from the bioanalytical reaction device  60 . 
     While the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive; the invention is not limited to the disclosed embodiment. Other variations to the disclosed embodiment can be understood and effected by those skilled in the art and practising the claimed invention, from a study of the drawings, the disclosure, and the appended claims. In the claims, the word “comprising” does not exclude other elements or steps, and the indefinite article “a” or “an” does not exclude a plurality. A single processor or controller or other unit may fulfill the functions of several items recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. Any reference signs in the claims should not be construed as limiting the scope.