Patent Publication Number: US-2006018363-A1

Title: Disposable sample carrier for use with thermal sensors

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS  
      This application claims benefit of U.S. provisional patent application Ser. No. 60/585,170, filed Jul. 2, 2004. 
    
    
     TECHNICAL FIELD OF THE INVENTION  
      The present invention relates to disposable sample carriers to be used with thermal sensors for forming a thermal sensor system as well as methods of using disposable carriers with thermal sensors.  
     BACKGROUND OF THE INVENTION  
      A number of different types of thermal or temperature sensors exist. Two of the most common types are thermocouples and thermoresistors or thermistors.  
      In a thermocouple sensor the measurement of temperature is realised by what is known as the Seebeck effect, the physics of which is rather complicated. The basic idea of this Seebeck effect is that when two dissimilar materials, for example two dissimilar metals (e.g. copper and iron) are brought together in a circuit, and the junctions are held at different temperatures, then a small voltage is generated and an electrical current flows between them. The potential created by the temperature difference in the materials is measured by a voltmeter. The magnitude of the potential depends on the temperature difference of the two junctions and the composition of the materials.  
      A thermoresistor measures the temperature by measuring the change in electrical resistance that occurs in a material, e.g. a metal, as it heats up. The electrical resistance of materials such as metals varies with their temperature. Therefore, the temperature can be measured by measuring the resistance of a piece of such a material. The main benefits of thermocouples and thermoresistors are that they are easy to isolate thermally from the remainder of a measurement device, which means not only a more accurate temperature measurement but also a faster response to changes in temperature.  
      One of the more interesting applications of thermal sensors is that they can be used for measuring fluid flow. The basic concept behind these sensors is that the volume flow rate of a fluid, i.e. how much volume flows past a pre-determined point in a small interval of time, can be measured by heating the flow and measuring the dissipation of heat in the flow. An example of a thermal sensor that can be used for these applications is a calorimetric flow sensor. It works by measuring the temperature of the fluid at a first point, heating the fluid at a second point, and then re-measuring the temperature of the fluid at a third point. If the fluid flows fast, the temperature at the third point will be higher than the temperature at the first point. If the fluid is flowing slowly, the heat will be more evenly distributed in the fluid and the measured temperature difference between the two sensors will be smaller.  
      In the above-described thermal sensors the fluid to be measured is in direct contact with the sensor and can contaminate the sensor. Therefor, these sensors have to be cleaned after each measurement.  
     SUMMARY OF THE INVENTION  
      It is an object of the present invention to provide a thermal sensor system with improved properties. An advantage of the present invention is the provision of methods of using disposable carriers with thermal sensors.  
      The above objective is accomplished by a method and device according to the present invention.  
      The present invention provides a thermal sensor system comprising: 
          a thermal sensor having a top surface, and     a first disposable sample carrier, 
 
 wherein the first disposable sample carrier is located on or above the top surface of the thermal sensor. 
       

      An advantage of the thermal sensor system according to the present invention is that it prevents cross-contamination of the thermal sensor as the sample to be measured is never in direct contact with the thermal sensor, but is in contact with the disposable sample carrier, which is removed after use.  
      Furthermore, the thermal sensor system according to the present invention is cost effective, because the thermal sensor itself can be re-used after it has been used to perform a measurement, as only the sample carrier has to be removed in between two subsequent measurements.  
      According to embodiments of the invention, a distance d exists between the first disposable sample carrier and the top surface of the thermal sensor. The distance d may be between 0 and 400 μm. Preferably, the distance d may be between 0 and 200 μm, more preferably between 0 and 100 μm and most preferably between 0 and 10 μm. The smaller the distance d is, the better the sensitivity of the thermal sensor system becomes.  
      According to an embodiment of the invention, the distance d may be varied by means of spacers located in between the first disposable sample carrier and the top surface of the thermal sensor. In that case, the distance d between the first disposable sample carrier and the top surface of the thermal sensor may be varied by varying the height of the spacers.  
      In a preferred embodiment according to the invention, the first disposable sample carrier may be in direct contact with the top surface of the sample carrier. In this case, the sensitivity of the thermal sensor system does not significantly differ from the sensitivity of a thermal sensor without a sample carrier.  
      According to embodiments of the invention, the thermal sensor system may furthermore comprise a take-up roll and a dispensing roll for providing a continuous system of providing and removing clean parts of first disposable sample carrier. In that way, no interruption is required in between two subsequent measurements. After a measurement, the first disposable sample carrier that has been used is moved toward the take-up roll while unused clean parts of the disposable sample carrier coming from the dispensing roll are provided at the location of the thermal sensor before performing another measurement.  
      In embodiments of the invention, the thermal sensor system may furthermore comprise a second disposable sample carrier having a top surface. The first disposable sample carrier may also comprise a top surface and the second disposable sample carrier may be positioned with its top surface toward the top surface of the first disposable sample carrier. An advantage of these embodiments is that they allow mixing of different samples before or during measurements are performed and that they allow for thermal equilibrium to be established between two samples.  
      In another embodiment according to the invention, an intermediate foil may be present in between the first and second disposable sample carriers. For example, the intermediate foil may comprise pores and may allow partial mixing of samples before or during measurements and furthermore allows, besides for a thermal equilibrium, also for a chemical equilibrium to be established.  
      In further embodiments of the invention, the disposable sample carrier may comprise a frame, for example a plastic frame, comprising wells for receiving samples. The frame may form, in one embodiment, a micro-plate. This frame allows an accurate position of the samples with respect to the thermal sensor and thus leads to a higher sensitivity.  
      According to the invention, the thermal sensor system may furthermore comprise a dispenser means for dispensing samples onto the top surface of the first and/or second sample carrier. The dispensing means may be any suitable dispensing means known by a person skilled in the art.  
      The present invention also includes the use of disposable carriers for samples especially foil carriers with thermal sensors.  
      Particular and preferred aspects of the invention are set out in the accompanying independent and dependent claims. Features from the dependent claims may be combined with features of the independent claims and with features of other dependent claims as appropriate and not merely as explicitly set out in the claims.  
      The above and other characteristics, features and advantages of the present invention will become apparent from the following detailed description, taken in conjunction with the accompanying drawings, which illustrate, by way of example, the principles of the invention. This description is given for the sake of example only, without limiting the scope of the invention. The reference figures quoted below refer to the attached drawings.  
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       FIG. 1  is a schematic illustration of a first embodiment of the present invention.  
       FIG. 2  is a schematic illustration of a second embodiment of the present invention.  
       FIG. 3  illustrates the set-up of the experiment used for producing the graph shown in  FIG. 4 .  
       FIG. 4  shows a comparison between signals obtained from samples directly on the chip, i.e. without a disposable sample carrier in between the sample and the sensor, and signals acquired with a thermal sensor system according to an embodiment of the invention.  
       FIG. 5  is a schematic illustration of a further embodiment of the present invention.  
       FIG. 6  illustrates a disposable microplate in top view and in cross-section. 
    
    
      In the different figures, the same reference signs refer to the same or analogous elements.  
     DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS  
      The present invention will be described with respect to particular embodiments and with reference to certain drawings but the invention is not limited thereto but only by the claims. The drawings described are only schematic and are non-limiting. In the drawings, the size of some of the elements may be exaggerated and not drawn on scale for illustrative purposes. The dimensions and the relative dimensions do not correspond to actual reductions to practice of the invention.  
      Furthermore, the terms first, second, third and the like in the description and in the claims, are used for distinguishing between similar elements and not necessarily for describing a sequential or chronological order. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in other sequences than described or illustrated herein.  
      Moreover, the terms top, bottom, over, under and the like in the description and the claims are used for descriptive purposes and not necessarily for describing relative positions. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in other orientations than described or illustrated herein.  
      It is to be noticed that the term “comprising”, used in the claims, should not be interpreted as being restricted to the means listed thereafter; it does not exclude bther elements or steps. It is thus to be interpreted as specifying the presence of the stated features, integers, steps or components as referred to, but does not preclude the presence or addition of one or more other features, integers, steps or components, or groups thereof. Thus, the scope of the expression “a device comprising means A and B” should not be limited to devices consisting only of components A and B. It means that with respect to the present invention, the only relevant components of the device are A and B.  
      The invention will now be described by a detailed description of several embodiments of the invention. It is clear that other embodiments of the invention can be configured according to the knowledge of persons skilled in the art without departing from the true spirit or technical teaching of the invention, the invention being limited only by the terms of the appended claims.  
      The present invention provides a thermal sensor system comprising a disposable sample carrier and a thermal sensor, such as a thermal detector and/or enthalpy chip and/or array. The thermal detector may, for example, be a thermopile junction, a diode, a thermistor or any other temperature dependent material or sensor. An idea behind the present invention is to provide disposable sample carriers that are put on or above the sensor chips, the sample carriers being of a material and with dimensions so that the thermal path between the sample and the thermal sensor is only changed to a small degree due to the use of the sample carrier, and that the sensitivity of the thermal sensor is not significantly changed or not changed at all. A purpose of the thermal sensor system according to the invention may be to measure heat exchange and/or metabolic activity in solutions comprising soluble species.  
      According to the invention, a sample carrier, e.g. a foil, is provided for being located on or above a thermal sensor. According to the invention, the sample carrier, e.g. foil, may be cut to shape before being put, for example manually or mechanically, on or above a top surface of the thermal sensor, but it may also be continuously rolled over the top surface of the thermal sensor. Depending on the application, the distance between the sample carrier, e.g. foil, and the sensor surface may be varied. Preferably, the sample carrier may be as close as possible to the thermal sensor (see further).  
      A thermal sensor system  10  according to a first embodiment of the invention is illustrated in  FIG. 1 . The thermal sensor system  10  comprises a thermal sensor  1  having a top surface  2 . A sample carrier  3 , e.g. a foil, is provided on or above the top surface  2  of the thermal sensor  1 . The sample carrier  3 , e.g. foil, may, for example, comprise a polymer and may have a thickness of 1 μm or more, 5 μm or more, 10 μm or more, 15 μm or more, 20 μm or more, 50 μm or more, e.g. in the range 1 to 50 μm, or 5 to 50 μm or 10 to 20 μm. A suitable thickness of the sample carrier depends on the material used for the sample carrier, and on its thermal characteristics. The thickness of the sample carrier should be such that the thermal path between a sample and the thermal sensor is not substantially changed with respect to when no sample carrier would be present. For example, strong and thin polymer films of variable thickness suitable to be applied with the present invention are described in “Gossamer Spacecraft: membrane and inflatable structures and technology for space applications”, C. H. M. Jenkins, American Institute of Aeronautics and Astronautics, vol. 191, 2001.  
      Depending on the required application, the distance d between the sample carrier  3  and the thermal sensor  1  may be varied. The distance d between the sample carrier  3 , e.g. foil, and the top surface  2  of the thermal sensor  1  may be between 0 and 400 μm, preferably between 0 and 200 μm, more preferably between 0 and 100 μm and most preferably between 0 and 10 μm. In a preferred embodiment, when sensitivity is an important issue, the sample carrier  3 , e.g. foil, may be in direct contact with the top surface  2  of the thermal sensor  1 . In this case, a sensitivity comparable to the sensitivity of a thermal sensor without a foil can be obtained (see further). The distance d may be determined by the presence or absence of spacers (not shown in  FIG. 1  but illustrated in  FIG. 3 ) placed on the top surface  2  of the thermal sensor  1  and by the height of the spacers. When no spacers are present on the top surface  2  of the thermal sensor  1 , the foil  3  will stick directly to that top surface  2  because of its electrostatic charge.  
      A sample  4  to be measured may, for example in the form of liquid drops, be provided onto the top surface  5  of the sample carrier  3 , e.g. foil, by means of a dispenser means  6 . The addition of the sample  4  onto a part of the sample carrier  3 , e.g. foil, at the position of the thermal sensor  1  can be accomplished by any known or suitable dispensing technology. The sample  4  may, for example, be a solution comprising enzymes, glucose, maltose, yeast, or may be any other solution comprising soluble species.  
      In the example illustrated, the sample carrier  3 , e.g. foil, is stretched between a take-up roll  7  and a dispensing roll  8 . After a measurement is performed, the sample carrier  3 , e.g. foil, is driven in a direction as indicated by arrow  9  by a driving means (not shown in the figure). In that way, the sample carrier  3 , e.g. foil, is rolled onto the take up roll  7  and rolled off of the dispensing roll  8 , hence removing the used part of the sample carrier  3 , e.g. foil, away from the thermal sensor  1  and providing a clean part of sample carrier  3 , e.g. foil, at the position of the thermal sensor  1 . The used sample carrier  3 , e.g. foil, that is collected on the take-up roll  7  may then be removed from the take-up roll  7 , e.g. after cutting, and thrown away.  
      It has to be understood that this is only an example. In other embodiments according to the invention, the sample carrier  3 , e.g. foil, may be cut before it is applied above or on the top surface of the thermal sensor  1 . In this case, the sample carrier  3 , e.g. foil, may, for example, be manually applied or may be applied in any other suitable way. In that case, the presence of a take-up roll  7  and a dispensing roll  8  is not required.  
      According to embodiments of the invention, samples  4  may be placed between a stack of sample carriers  3 , e.g. foils, and these stacks may be such as to allow for partial or full mixing of different species at certain locations and times. In a second embodiment according to the invention, two sample carriers  3   a ,  3   b , e.g. foils, may be used, instead of one as in the first embodiment, on each of which samples  4   a ,  4   b  have been dispensed. This is illustrated in  FIG. 2 .  
      According to this second embodiment, the thermal sensor system  10  comprises, similar to the thermal sensor system  10  according to the first embodiment, a thermal sensor  1  and a first sample carrier  3   a , e.g. foil, with first samples  4   a  dispensed on its top surface  5   a  located on or above the top surface  2  of the thermal sensor  1 . The first sample carrier  3   a , e.g. foil, may, for example, comprise a polymer and may have a thickness of 1 μm or more, 5 μm or more, 10 μm or more, 15 μm or more, 20 μm or more, 50 μm or more, e.g. in the range 1 to 50 μm, or 5 to 50 μm or 10 to 20 μm. A suitable thickness of the sample carrier depends on the material used for the sample carrier, and on its thermal characteristics. The thickness of the sample carrier should be such that the thermal path between a sample and the thermal sensor is not substantially changed with respect to when no sample carrier would be present. For example, strong and thin polymer films of variable thickness suitable to be applied with the present invention are described in “Gossamer Spacecraft: membrane and inflatable structures and technology for space applications”, C. H. M. Jenkins, American Institute of Aeronautics and Astronautics, vol. 191, 2001. Depending on the application, the distance d between the first sample carrier  3   a  and the thermal sensor  1  may be varied. The distance d between the first sample carrier  3   a , e.g. foil, and the top surface  2  of the thermal sensor  1  may be between 0 and 400 μm, preferably between 0 and 200 μm, more preferably between 0 and 100 μm and most preferably between 0 and 10 μm. In a preferred embodiment and when sensitivity is an important issue, the first sample carrier  3   a , e.g. foil, may be in direct contact with the top surface  2  of the thermal sensor  1 . The distance d may be determined by the presence or absence of spacers placed on the top surface  2  of the thermal sensor  1  and by the height of the spacers. When no spacers are present on the top surface  2  of the thermal sensor  1 , the foil  3  can stick directly to that top surface  2  because of its electrostatic charge.  
      The thermal sensor system  10  according to the second embodiment furthermore comprises a second sample carrier  3   b , e.g. foil, with second samples  4   b  dispensed on its top surface  5   b . The second sample carrier  3   b  is located with its top surface  5   b  oriented towards the top surface  5   a  of the first sample carrier  3   a , e.g. foil (see  FIG. 2A ). According to embodiments of the invention, the first samples  4   a  and second samples  4   b  may be the same or may be different. In the case that the first and second samples  4   a ,  4   b  are the same, these may be used as blanco or calibration samples. The first and second samples  4   a ,  4   b  may, for example, be a solution comprising enzymes, glucose, maltose, yeast, or may be any other solution comprising soluble species. The second sample carrier  3   b , e.g. foil, may, for example, comprise a polymer and may have a thickness of 1 μm or more, 5 μm or more, 10 μm or more, 15 μm or more, 20 μm or more, 50 μm or more. A suitable thickness of the second sample carrier  3   b  depends on the material used for the sample carrier  3   b , and on its thermal characteristics. For example, strong and thin polymer films of variable thickness suitable to be applied with the present invention are described in “Gossamer Spacecraft: membrane and inflatable structures and technology for space applications”, C. H. M. Jenkins, American Institute of Aeronautics and Astronautics, vol. 191, 2001.  
      An advantage of a thermal sensor system  10  comprising two sample carriers  3   a ,  3   b  positioned as described above is that it allows for the establishing of thermal equilibrium between two samples and it also allows for mixing of two samples before or during measurements are performed.  
      Optionally, a removable intermediate barrier means, e.g. a removable foil, may be provided in between the first and second sample carrier  3   a ,  3   b , e.g. foil. The removable intermediate barrier means, e.g. foil, may form a semi-permeable membrane to accomplish a partial equilibrium. Semi-permeable membranes may be based on synthetic or natural products and can include woven, non-woven or sheet material. Examples of suitable permeable materials can, for example, be found in “New materials permeable to water vapour”, H. Trübel, springer, 1999, in “Diffusion in and through polymers”, W. R. Vieth, Hanser, 1991, and in “Biomaterials”, S. V. Bhat, Alpha Science, 2002. An advantage of the use of an intermediate foil  11  allows for the establishing of, besides a thermal equilibrium, a chemical equilibrium and allows for partial or full mixing of samples before or while measurements are performed.  
      The thermal sensor system  10  according to the second embodiment may, for example, be used for partially or completely mixing two samples  4   a ,  4   b . This is further illustrated in  FIGS. 2B and 2C .  
      The first sample carrier  3   a , e.g. foil, and the second sample carrier  3   b , e.g. foil, are brought closer together. This may be obtained e.g. by a driving system (not illustrated) for applying a translational movement to the take-up and dispensing rolls  7 ,  8 . Partial equilibrium can be achieved by letting the first and second samples  4   a ,  4   b  come into contact with each other by means of an intermediate barrier means, for example through an intermediate foil  11 . In this case, the intermediate foil  11  may be made of a material comprising pores. The pore size and/or other pore characteristics may be chosen so as to allow molecules present in the first and second sample  4   a ,  4   b  to reach chemical equilibrium, except for the species to be determined. This means that, in the example given in  FIG. 2 , the intermediate foil  11  may have a different permeability for different species in the samples  4   a ,  4   b . After chemical equilibrium is established between the first and second samples  4   a ,  4   b , the intermediate foil  11  may be removed in order to allow the species to be measured to come into contact with one another once this partial equilibrium between the other species present in the samples  4   a ,  4   b  has been set.  
      According to the second embodiment, the first and second sample carrier  3   a ,  3   b , e.g. foil, may be provided with a further take up roll  7  and with a further dispensing roll  8 . If the semi-permeable film or intermediate barrier means, e.g. foil  11 , has to move with the other films, this intermediate barrier means, e.g. foil  11  may also be provided with yet a further a take up roll and yet a further dispensing roll  8  (not shown in the figure).  
      In  FIG. 1  and  FIG. 2  the sample carrier  3 ,  3   a , e.g. foil, is positioned above the top surface  2  of the thermal sensor  1 . However, in other embodiments, the sample carrier  3 ,  3   a , e.g. foil, may be positioned at the top surface  2  of the thermal sensor  1  and may be in direct contact with that top surface  2 . In that case, according to embodiments of the invention, the sample carrier  3 ,  3   a , e.g. foil, may take the shape of structures present on the top surface  2  of the thermal sensor  3 ,  3   a , e.g. foil, or because the relevant shapes have been formed in the sample carrier  3 ,  3   a , e.g. foil, e.g. by deformation of the material. For example, if recipients, wells or reaction vessels are present on the thermal sensor, the sample carrier  3 ,  3   a , e.g. foil, may be put on the sensor in a way that the sample carrier  3 ,  3   a , e.g. foil, takes the shape of the vessels, or in a way that the sample carrier  3 ,  3   a , e.g. foil, comprises shapes which fit into the wells or in a way that the sample carrier  3 ,  3   a , e.g. foil, is spun over the wells.  
      In  FIG. 3 a  thermal sensor system  10  according to a third embodiment of the invention is illustrated. The thermal sensor system  10  comprises a thermal sensor  1  comprising thermopiles  12  and a membrane  13 . The membrane  13  may have a thickness of, for example, 4 μm. On the top surface  2  of the thermal sensor  1  at least one spacer  14   a - e  is positioned. The spacers  14   a - e  may be positioned on the top surface  2  of the thermal sensor  1  such that equal spaces are present in between neighbouring spacers  14   a - e . In alternative embodiments, the spacers  14   a - e  may also be positioned such that non-equal spaces are present in between neighbouring spacers  14   a - e . This is the case in the example given in  FIG. 3 . In this figure, the distance d s1  between spacer  14   a  and  14   b  and the distance d s4  between spacer  14   d  and  14   e  may, for example, be 4.25 mm, the distance d s2  between spacer  14   b  and  14   c  and the distance d s3  between spacer  14   c  and  14   d  may, for example, be 2.38 mm. It has to be understood that this is only an example and is not intended to limit the invention. The height h of the spacers  14   a - e  determines the distance between the sample carrier  3 , e.g. foil, and the thermal sensor  1 . The at least one spacer  14   a - e  may have a height h of between 0 and 400 μm. Preferably, the at least on spacer  14   a - e  may have a height h of between 0 and 200 μm, more preferred the at least one spacer  14   a - e  may have a height h of between 0 and 100 μm and most preferred the at least one spacer  14   a - e  may have a height h of between 0 and 10 μm.  
      On the top surface  15  of the spacers  14   a - e  a thin sample carrier  3 , e.g. foil, is positioned. The sample carrier  3 , e.g. foil, may, for example, comprise a polymer and may have a thickness of 1 μm or more, 5 μm or more, 10 μm or more, 15 μm or more, 20 μm or more, 50 μm or more, and may comprise, for example, a polymer. For example, strong and thin polymer films of variable thickness suitable to be applied with the present invention are described in “Gossamer Spacecraft: membrane and inflatable structures and technology for space applications”, C. H. M. Jenkins, American Institute of Aeronautics and Astronautics, vol. 191, 2001.  
      Samples  4  may be dispensed onto the sample carrier  3 , e.g. foil, by any suitable dispensing method known by persons skilled in the art. The samples  4  may preferably be located in the spaces in between the spacers  14   a - e  such that optimal measurement by the thermal sensor  1  can be performed.  
      In  FIG. 4  signals  20  obtained from a thermal sensor system  10  comprising a thermal sensor  12  (type Vivactis MiDiCal chip) and a sample carrier  3 , e.g. foil, as illustrated in  FIG. 3  are compared with signals  21  obtained from a same thermal sensor  1  (type Vivactis MiDiCal chip) without a sample carrier  3 , e.g. foil. From this figure it can be seen that the signal height is reduced to about 50% of the signal when the sample  4  is put on the sample carrier  3 , e.g. foil, at a height of, in the example given, 400 μm above the thermal sensor  1  rather than directly on the thermal sensor  12 .  
      When the height h between the sample carrier  3 , e.g. foil, and the thermal sensor  1  is decreased, the loss in sensitivity is decreased as well. Therefore, in accordance with the present invention, the distance d between the sample carrier  3 , e.g. foil, and the thermal sensor  1  may be between 0 and 400μ, preferably the distance between the foil  3  and the thermal sensor  1  may be between 0 and 200 μm, more preferably between 0 and 100 μm and most preferably between 0 and 10 μm.  
      A thermal sensor system  10  according to a further embodiment of the invention is illustrated in  FIG. 5 . In this example, the thermal sensor  1  comprises a thermopile  12  located on a membrane  13 . The thermal sensor system  10  furthermore comprises a sample carrier  3  which in the example illustrated comprises a frame  17 , e.g. a Si frame, or a plastic frame, with wells  18 , such as e.g. a micro-plate. Such disposable micro-plate is illustrated in  FIG. 6 . Samples  4  are dispensed in the wells  18  in the frame  17 , e.g. micro-plate. An advantage of this embodiment is that samples  4  can be very accurately dispensed onto the thermal sensor system  10 .  
      In the example illustrated, the frame  17  is positioned on the top surface  2  or at a distance d from the top surface  2  of the thermal sensor  1 . Depending on the application, the distance d between the sample carrier  3  and the thermal sensor  1  may be varied. The distance d between the sample carrier  3 , and the top surface  2  of the thermal sensor  1  may be between 0 and 400 μm, preferably between 0 and 200 μm, more preferably between 0 and 100 μm and most preferably between 0 and 10 μm. In a preferred embodiment and when sensitivity is an important issue, the sample carrier  3 , may be in direct contact with the top surface  2  of the thermal sensor  1 . The distance d may be determined by the presence or absence of spacers placed on the top surface  2  of the thermal sensor  1  and by the height of the spacers. When no spacers are present on the top surface  2  of the thermal sensor  1 , the sample carrier  3 , e.g. the wells  18  of the frame  17 , will stick directly to the top surface  2 . The thermal sensor system  10  according to the present invention has the advantage that it prevents cross-contamination, i.e. as the samples to be measured do not make direct contact with the thermal sensor  1 , they cannot contaminate the sensor  1 . Therefore, the sensor  1  does not have to be thrown away after a measurement or does not have to be cleaned in between subsequent measurements. This is time saving and cost effective. Therefore, the thermal sensor system  10  according to the present invention is suitable for use in, for example, biomedical or pharmaceutical applications.  
      It is to be understood that although preferred embodiments, specific constructions and configurations, as well as materials, have been discussed herein for devices according to the present invention, various changes or modifications in form and detail may be made without departing from the scope and spirit of this invention.  
      All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent or patent application was specifically and individually indicated to be incorporated by reference.