WO2014064040A1 - System for carrying out a contactless measurement on a sample and sample carrier - Google Patents

Abstract

A sample carrier (14) is used for performing contactless measurement on a sample (12), on which sample carrier the heating tracks (20) on the substrate (15) form a parallel circuit between the first and the second heating terminal (16, 18), such that when a sample (12) placed on the sample carrier (14) is heated by application of a voltage between the first and the second heating terminal (16, 18) the heating properties of the sample carrier (14) are not impaired even if isolated breaks are present in the heating tracks (20) because of process variations in the production of the heating tracks (20) for instance. In one example of a sample carrier (14), the density of the heating tracks (20) increases from the centre of the substrate (15) area outwards. In this way, it is possible to avoid the otherwise frequently occurring inhomogeneities in the heating profile across the substrate (15), according to which the heating generally declines towards the edge of the substrate (15).

Description

 System for carrying out a non-contact measurement on a sample and sample carrier

description

The present invention relates to non-contact measurements on samples such as e.g. biological and / or chemical samples, systems for such measurements, and sample carriers suitable for such systems.

It is believed that μΤΑ8 (Micro Total Analysis Systems) or lab-on chips are used in areas such as microsystems. global health and medical research will play an important role. You reduce costs and time for testing and analysis. The limitation that they are disposable, material selection, design, and manufacturing are all aspects that must be considered in order to keep chip costs low and thus produce a device with marketability. Numerous biological and chemical assays are temperature dependent, e.g. PCR (Polymerase Chain Reaction) and MCA (Melting Curve Analysis). When such a study is scaled down to micro size, precise temperature control and thermal homogeneity of integrated miniaturized heating and sensing elements in microfluidic features become critical factors for a functional device.

Microheating devices are ubiquitous in various MEMS and microfluidic devices. The latter provide various functions in physical or chemical sensors (SC Roth, YM Choi and SY Kim Sensors Actuators A, 2006, 128, 1-6, D. Briand, S. Colin and A. Gangadharaiah, Sensors Actuators A, 2006, 132, 317-24), chemical reactors (T. Becker, S. Muhlberger and W. Benecke, J. Microelectromech., Syst. 200, 9, 478-84, A. Splinter, J. Sturmann and O. Bartels, Sensors Actuators B, 2002, 83, 169-74) or pumps (Z. Yin and A. Prosperetti, J. Micromech., Microeng., 2005, 1683-91), etc. A typical layout of a micro-heater is a thin metallic or doped Si layer, which is patterned in a serpentine form on a dielectric substrate. A temperature measurement can be made possible by integration of a second trace or by a four-point measurement. Different applications have different limitations, but generally thermal homogeneity across the heated surface is important for accurate measurements and controls. But that is not easy to achieve on the basis of physical facts. Material selection and heater design are factors that may be modified to affect heat distribution in the heated area (W.-J. Hwang, KS Shin, and JH Roh. Sensors, 2011, 11, 2580-2591, D. Caputo, G. de Cesare and M. Nardini, IEEE SENSORS JOURNAL, 2012, 12 (5), 1209-13, http://www.allflexheaters.com/Profiled Heaters.cfm).

For biological applications, optical transparency of the substrate allows on-line monitoring and observation of the sample. Transparent heating elements for lab-on-chip applications were prepared by patterning ITO (indium tin oxide) on glass (K. Sun, A. Yamaguchi and Y. Ishida, Sensor and Actuators B, 2002, 84, 283 -289, J.-Y. Cheng, M.-H. Yen and C.-T. Kuo, Biomicrofluidics, 2008, 2, 024105- (1-12), J.-L. Lin, M.-H. Wu and C.Y. Kuo, Biomed Microdevices, 2010, 12, 389-398, S. Kumar Jha, R. Chand and D. Han, Lab Chip, 2012, doi: 10.1039 / C2LC40727B). However, due to its low abundance in the earth's crust, ITO is relatively expensive and therefore unsuitable for low cost diagnostics.

Transparent electrodes are also used in a large range of optoelectronic components, such as organic LEDs, photovoltaic cells and liquid crystal displays, essential elements that serve to generate voltage for the optoelectronic or electro-optical conversion. In these areas, metal meshes have been used as semi-transparent electrode materials to replace the commonly used ITO in the search for a more favorable electrode material (M.G. Kang and LJ Guo, Advanced Materials, 2007, 19 (10), 1391-1396, M G-Kang, MS, Kim and J Kim, Advanced Materials, Adv. Mater., 2008, 20, 4408-4413) or to reduce resistance and improve electrical homogeneity of the material (S. Choi, WJ Potscavage, Jr. and B. Kippelen, JOURNAL OF APPLIED PHYSICS, 2009, 106, 054507). PolylC has filed a patent application for transparent conductive surfaces made of metal meshes for photovoltaic, display and LED applications (WO 2010/108692 A2). Further, metal nets have been used for decades (J. Zhang, PAR Ade and P. Mauskopf, Appl. Opt 201 1, 50 (21), 3750-7; PAR Ade, G. Pisano and C. Tucker, Proc. OssPIE Vol. 6275 62750U-1) in FIR and sub-millimeter astronomy instruments. As mentioned above, there are already sample carriers in which a heating track is formed meandering on a substrate. The problem with these sample carriers, however, is that interrupting the conductor path for the heating device would inevitably result in the latter losing its function. This increases the Production costs, because either in the manufacture dimensions, material order, etc. must be set with more safety margins to otherwise possible limits, or the production must be monitored consuming, which in turn precludes the goal of the lowest possible production costs. A further disadvantage of a meandering guidance of the heating track over the substrate of the sample carrier is the inherent surface density increase at those edges of the substrate where the meandering shape has its loop reversal points.

The object of the present invention is therefore to provide a system and a method for carrying out a non-contact measurement of a sample as well as a sample carrier with improved characteristics.

This object is solved by the subject matters of the independent claims. According to a first aspect of the present invention, when carrying out a non-contact measurement on a sample, a sample carrier is used, in which the heating paths on the substrate form a parallel connection between the first and the second heating termination, so that when by applying a voltage between the first and the second heating terminal is heated, a sample applied to the sample carrier, the heating properties of the sample carrier are not affected even if individual interruptions of the heating paths due to, for example, process variations in the production of the heating tracks are present.

If the heating paths even form a two-dimensional lattice structure, isolated interruptions and cross-sectional constrictions of the heating lanes have a less negative effect on homogeneity of the sample heating via the heating region of the substrate covered by the heating lanes, since their occurrence in individual lugs of the two-dimensional lattice is limited by the lattice structure or lattice structure adjacent bridges are bridged. It is thus possible to reduce the manufacturing tolerances in favor of lower production costs. Furthermore, it is possible to make the heating paths optically intransparent, and nevertheless to maintain a semitransparency of the sample carrier with any transparency of the substrate present, since the grid interspaces or meshes of the two-dimensional lattice preserve the transparency of the substrate in the thickness direction of the substrate.

According to a further aspect, a sample carrier is provided in which the heating tracks are arranged in such a way that the area density of the heating tracks increases from the center of the substrate to the outside. That way it's possible to do the otherwise often occurring inhomogeneities of the heating profile across the substrate, after which usually the heating decreases at the edge of the substrate to avoid.

Further preferred embodiments of the present invention are the subject of the dependent claims. Preferred embodiments of the present invention will be further explained below with reference to the figures, in which

1 is a schematic drawing of a system for carrying out a contactless measurement on a sample according to an embodiment;

FIG. 2 is a schematic plan view of a sample carrier according to an embodiment; FIG. FIG. 3 shows a schematic plan view of a sample carrier according to an alternative exemplary embodiment with outwardly increasing heater path density; FIG.

4a shows a schematic plan view of a sample carrier according to an alternative embodiment with non-rectilinear grid bars;

4b is a schematic plan view of a sample carrier 14 according to an embodiment with complete representation of the substrate front side;

4c is a schematic plan view of a sample carrier according to an exemplary embodiment with non-linear extension of the Heizbahngitternetzes;

4 shows a schematic side sectional view of a sample carrier according to an embodiment, in which a protective layer covers the heating paths; 4e shows a schematic view of a sample carrier according to an embodiment, in which the side of the substrate provided with the heating paths together with a cover element forms at least one channel or chamber to which the heating area adjoins; 5 shows a flow chart of a method for carrying out a non-contact measurement on a sample according to an exemplary embodiment; 6a and 6b show a schematic plan view and an associated heating distribution of a sample carrier with a meandering guided heating path;

, FIGS. 7a and 7b show a schematic top view and an associated heating distribution of a sample carrier with exemplary square meshes in the heating grid lattice: and FIGS

8a and 8b show a schematic plan view and an associated heating distribution of a sample carrier with narrower square heating grid systems than FIGS. 7a and 7b.

1 shows a system 10 for performing a non-contact measurement on, for example, a biological and / or chemical sample 12. The sample may be, for example, a liquid, such as a solution, a suspension or the like. For example, sample 12 contains a particular analyte. However, sample 12 could also be a solid, such as a sediment. The analyte mentioned above can be atoms, molecules or other substances of any kind, such as biological cells, DNA, gene-antigen compounds, etc. The following is without limitation and merely for the sake of clarity assumed that it Sample 12 is a biological / chemical sample.

The system includes a sample carrier 14 having a substrate 15, first and second heating ports 16 and 18, and heating paths 20. The heating paths 20 are disposed on the substrate 15, such as a front side 22 thereof. The heating connections 16 and 18 can also be arranged on the same front side 22, but according to an alternative, the latter are arranged on a rear side 24 of the substrate 15 facing away from the front side 22 or on a side surface of the substrate 15. As will be described in more detail below is, the heating tracks 20 on the substrate form a parallel connection between the heating terminals 16 and 18, so that the biological / chemical sample can be heated after applying the same to the sample carrier 14 by applying a voltage between the heating terminals 16 and 18. The system 10 further comprises a measuring arrangement 26 for carrying out a contactless measurement on the biological / chemical sample 12. In FIG. 1 it is indicated as an optical measuring arrangement with a light source 28 and an optical system 30 for carrying out a transmissive optical measurement, namely for the optical Observation through A user of the system, but there are a variety of alternatives, such as other optical measurements, such as reflective measurements, interferometric measurements, or non-optical measurements. It should be noted that, although in Fig. 1, the sample 12 was shown as being applied to the front side 22 and the heating tracks 20, the application for carrying out the non-contact measurement could also take place on the rear side 16. In any case, the application is made such that, in a projection along a thickness direction of the substrate 15, the sample 12 and the heating area 32 laterally covered by the heating paths 20 overlap.

FIG. 2 shows by way of example a plan view of the front side 22 of the substrate 15 in order to show a possible embodiment of the heating tracks 20 and their guidance on the front side 22. 2 shows the heating connections 16 and 18 and the heating paths 20 between them. According to the exemplary embodiment of FIG. 2, the heating paths 20 form a two-dimensional lattice structure of conductor lattice web sections 34 which meet at lattice nodes and grid interspaces or meshes 36, which are enclosed by not further reducible loops of webs 34, and in which the grid of heating paths 20, the substrate 15 can be exposed. In the case of Figure 2, the grid interstices 36 are exemplified to be square in shape, but in alternative embodiments could also have other shapes, such as rectangular, circular, hexagonal, or similar shapes. The webs 34 may, depending on which mesh shape is present, have a cross section that is constant along their length between the respective lattice nodes 40 or a variable cross section, for example, but a constant thickness, especially in a direction transverse to their length. The number of lattice webs 34 meeting in the lattice node 40 may differ among the nodes 36, depending, for example, on whether the node is at the edge of the lattice or not. The shapes of the meshes 36 may be congruent to one another, but need not. They also need not have a similar shape, as is still the case in an embodiment described below.

As a result of the fact that the heating paths 20 according to FIG. 2 form a two-dimensional lattice structure, any interruptions of the heating paths 20, as shown by way of example in FIG. 2 at 38 in a web of the lattice, or cross-sectional constrictions of the heating lanes 20 in webs of the web Be bridged so that no negative effects on the heating homogeneity over the heating region 32 away or are mitigated. While FIG. 2 shows a sample carrier in which the heating paths 20 form a two-dimensional lattice structure, which in turn forms a regular lattice in which a surface density of the heating lanes 20 across the surface 22 of the substrate in the region 32 is constant laterally constant surface density may not necessarily be. 3 shows an embodiment in which the two-dimensional lattice structure forms an irregular lattice in which an areal density of the heating lanes 20 increases outwardly from a lateral center of the irregular lattice, that is, the meshes 36 become smaller from the inside of the lattice toward the outside. Again, the mesh does not necessarily have to have similar shapes to each other. Rather, the shapes of the meshes can also differ from each other.

In the figures briefly described below, various other variants are shown by way of example. 4a shows, for example, that the webs 32 surrounding the meshes 36 of the lattice formed by the heating lanes 20 do not necessarily have to extend in a straight line between the lattice nodes 40, but may also be laterally curved. 4b shows that the heating connections 16 and 18 could be formed by electrodes which are arranged in opposite edge regions 42 and 44 of the rectangular or cuboid substrate 15 on the rectangular front side 22, for example. In other words, in the case of Fig. 4b, the heating area 32 is laterally between the heating ports 16 and 18. It may, as illustrated in Fig. 4b, be elongate to extend along its length between the heating ports 16 and 18 extend so that the latter are located at the two ends of the area 32. 4c shows an alternative in which the heating region 32 is elongated but bent along its length so as to extend non-rectilinearly like a web across the front face 22, with the thickness across the web width and the web length of the region 32 Heating paths 20 formed grids from one heating connection 16 to the other heating connection 18 extends. In FIG. 4c, the main connection 16 and the main connection 18 are located in the vicinity of the same shorter edge of the front side 22, which is rectangular by way of example here, by way of example.

Finally, FIG. 4 d merely shows an alternative embodiment of a sample carrier to FIG. 1, according to which a protective layer 46 covers the front side 22 of the substrate 15 and the heating paths 20 arranged thereon and, as is the case here by way of example, the electrodes 16 and 18. 4e still shows that the front side 22 of the substrate 15 does not necessarily have to be completely exposed for the sample. Rather, it is possible that the front side 22 is covered by, for example, a lid member 90, such that between Front side 22 of the substrate 15 and cover member 90, a channel or a chamber 92 is formed along the front side 22 along or adjacent to the front, in such a way that the heating region 32 adjacent to the channel or the chamber 92. In this way, the example liquid sample can be passed through the channel 92 to the heating region 32 or brought by filling in the chamber to the heating region 32. The lid member 90 may be, for example, a substrate of also transparent material. It may be glued to the front 22 or otherwise secured. Of course, the exemplary embodiment of FIG. 4e can be combined with the exemplary embodiment of FIG. 4d, ie it is also possible to provide the protective layer 22 for covering the heating tracks 20, wherein the protective layer can be, for example, an inert material. The material of the protective layer 22 may be, for example, a curable material such as polymer.

The substrate 15 of FIG. 1 is a substrate, preferably transparent to the light of the optical measuring system, of a transparent material, such as glass or the like. Of course, in the case of other measuring arrangements which work non-optically, the transparency could also be absent. The material of the heating sheets 20 does not necessarily have to be selected in terms of transparency. It does not necessarily consist of ITO. The material for the heating tracks 20 may be metal or a suitable semiconductor material. The application can be done by microlithography or otherwise. The substrate 15 may be rigid or flexible.

As is shown by way of example in FIG. 2, in order to carry out a four-point measurement, the sample carrier can additionally also have electrodes 50 and 52, which are formed integrally with the electrodes 16 and 18, respectively. A dashed line symbolized in Fig. 2 readout circuit 54 could detect a sensor value via these two electrodes 50 and 52, which could be a measure of a resistance of the heating paths 20. The readout circuit could be part of the system of FIG. 5 shows by way of example the sequence of a method for carrying out a non-contact measurement in a sample according to an exemplary embodiment. First, in a step 56, one of the sample carriers described above is provided. Subsequently, in a step 58, the sample is applied to the sample carrier. As stated, the application can take place on the front side 22 or on the rear side 24, but each overlap laterally with the heating region 32. Thereafter, in a step 60, the sample is heated by applying a voltage between the electrodes 16 and 18 and causing a current to flow through the heating paths 20. In one step 62 is then performed in the heated state of the sample, the non-contact measurement on the same.

In other words, the above embodiments have shown examples of a sample carrier that could serve as a heating element in biological or chemical applications. As material for the heating tracks 20 metal could be used. In the case of meshing, the metal mesh structure would then form an array of regular or gradually varying openings 36 in the form of, for example, squares or rectangles, as shown above, or circles or any kind of regular polygons , The heating tracks could in particular be formed from an electrically conductive thin-film layer, for example by structuring the same. The thin film layer could be applied to the transparent, rigid or flexible substrate 15 in different ways, for example. The structuring can also be done in different ways.

The applications of the above embodiments include samples in biology or chemistry. Biological applications, such as Proteomics, genetics and cell samples as well as bioreactors with the need for heating and optical transparency may be considered. Other applications may be hydrogels and other polymer systems that require temperature control.

Compared with conventional single-wire heating technologies, the above embodiments using a network structure of heating tracks have the following advantages: A network structure represents a higher manufacturing robustness compared to a meander / serpentine. If an interruption of a conductor in a meander would occur, the heater or sample carrier would lose its function while a network heater structure would still function because the electrical line is distributed over only a plurality of conductors or lands 32. In addition, the net heater is more tolerant of compensating for deviations from the design geometry of the conductor. For example, lead constraints due to etch defects lead to local high resistances and hot spots in a meandering structure. Instead, the network structure attempts to compensate for the source of nonuniformity by passing current away from the high resistance regions.

A meandering heater has a more circular hot spot when heated, while a mesh has a more rectangular shape, which is significant. For example, the mesh expands heat more efficiently relative to its own heater surface than a meander heater. Thus, using a mesh, a larger surface area can be uniformly heated. See for example Fig. 6 and 7. Fig. 6a shows a meandering device with 15 μιτι line / heating and 150 μηι space on a PEN film substrate and Fig. 6b shows their corresponding heat profile in a substrate on the thermochromic liquid crystal layer at 62 ° C. , The heater surface is 1.5 x 3 mm. In contrast, FIG. 7a shows a network heating device or a sample carrier with 15 μm line / heating path and 150 μm space on a PEN film substrate, and FIG. 7b shows its corresponding heat profile, as it results in a thermochromic liquid crystal layer at 62 ° C. The heater surface is 1, 5 x 3 mm ² . As can be seen, the heat distributes more evenly in the case of Fig. 7b.

The heat distribution on the overall heater surface can be further improved by using the array of gradually varying size geometries as in FIG. 3, where heat losses at the periphery of the heater can be compensated by increasing the number of heating lines.

By reducing the mesh size (thinner lines or ridges 32 and smaller openings or meshes 32), thermal homogeneity on the micro-scale (defined by dimensions that are much smaller than the substrate thickness) can be achieved (compare FIGS ). In this way, a heating device may be mounted on a substrate of low thermal conductivity, such as e.g. Glass or polymer, in only one metallization step; i.e. no additional heat spreading layer is required, which increases the manufacturing costs and limits the transparency. Fig. 8a shows in comparison with Fig. 7a a Netzerwännungsvorrichtung with 5 μιη line and 50 μηι space on a PEN film substrate and Fig. 8b shows their corresponding heat profile, as it results in a thermochromic liquid crystal layer at 62 ° C. The heater surface is 1.5 x 3 mm.

If one or more metal layers (eg vapor-deposited or sputtered) is used to form the tracks 20, one or more very thin layers will be sufficient to achieve the adequate resistance. This is particularly advantageous for samples where the heater topography interferes with further processing or, if integrated into fluidic structures, could interfere with flow characteristics in channels, such as in the case of Fig. 4e. The heating tracks do not have to be made of ITO, which is expensive. This consequently promotes cost-effective production, which is essential for diagnostic products.

A net has less resistance than a meander. Therefore, less voltage must be applied to the grid for a given heating power than to a meandering heater. This is an advantage for low supply voltage systems, especially battery powered portable devices.

Other alternatives to the above embodiments would of course be conceivable.

Claims

claims A system for performing a non-contact measurement on a sample, comprising: a sample carrier (14) having a substrate (20); a first and a second heating port (16, 18); and Heating tracks (20) which are arranged on the substrate (20) and form a parallel connection between the first and the second heating connection (16, 18), so that a sample applied to the sample carrier (14) by applying a voltage between the first and the second heating connection (16, 18) can be heated; and a measuring arrangement (26) for performing a non-contact measurement on the sample. The system of claim 1, wherein the heater tracks (20) form a two-dimensional grid structure extending between the first and second terminals. The system of claim 2, wherein the two-dimensional grid structure comprises a regular array of grid spaces (36), the grid spaces (36) having a similar shape of a square, rectangular or circular shape. The system according to claim 2 or 3, wherein the two-dimensional lattice structure forms a regular lattice in which an areal density of the heater lanes (20) is laterally constant. 5. The system according to claim 2 or 3, wherein the two-dimensional lattice structure forms an irregular lattice in which an areal density of the heater lanes (20) increases outwardly from a lateral center of the irregular lattice. The system of any one of claims 1 to 5, wherein the first and second heater terminals (16, 18) are formed by a first and a second electrode, the first and second electrodes disposed in opposite edge areas of the substrate (20) are. The system of claim 6, wherein the first electrode is integrally connected to a third electrode disposed laterally adjacent to the first electrode on the substrate (20) and the second electrode is integrally connected to a fourth electrode laterally adjacent of the second electrode is arranged on the substrate (20), so that an electrical measurement between the third and fourth electrode is possible. The system of claim 7, wherein the system further comprises a controller and a readout circuit, wherein the controller is configured to apply a voltage for a heating current through the heater tracks (20) via the first and second electrodes (A, B) wherein the readout circuit is adapted to detect via the third and the fourth electrode a sensor value which is a measure of a resistance of the heating tracks (20). The system of any one of claims 1 to 8, wherein the heater tracks (20) are formed of a patterned electrically conductive thin film layer on the substrate (20). 10. The system according to one of claims 1 to 9, wherein the measuring arrangement (26) is designed to perform a measurement on the sample by means of light, and the substrate (20) of the sample carrier (14) is transparent to the light. The system of any one of claims 1 to 10, wherein the substrate (20) of the sample carrier (14) is flexible. 12. A method for performing a non-contact measurement on a sample, comprising the following steps: Providing a sample carrier (14) with a substrate (20); a first and a second heating port (16, 18); and a plurality of heater tracks (20) disposed on the substrate (20) forming a parallel connection between the first and second heater terminals (16, 18); Applying the sample to the sample carrier (14); Heating the sample by applying a voltage between the first and second heater terminals (16, 18); and Carrying out the non-contact measurement on the sample. A sample carrier (14) for a sample comprising: a substrate (20); a first and a second heating port (16, 18); and Heating tracks (20) which are arranged on the substrate and form a parallel connection between the first and the second heating connection (16, 18), wherein the heating paths (20) are arranged such that an areal density of the heating paths (20) from a center of the area Substrate increases towards the outside. The sample carrier (14) of claim 13, wherein the heater tracks (20) form a two-dimensional grid structure extending between the first and second terminals. The sample carrier (14) of claim 14, wherein the two-dimensional grid structure comprises an array of grid interspaces (36) having a similar shape of a square, rectangular or circular shape. The sample carrier (14) according to claim 14 or 15, wherein the two-dimensional lattice structure forms an irregular lattice in which an areal density of the heater lanes (20) increases outwardly from a lateral center of the irregular lattice. The sample carrier (14) according to any one of claims 1 to 16, wherein the first and second heater terminals (16, 18) are formed by first and second electrodes, the first and second electrodes being disposed in opposite edge portions of the substrate (20 ) are arranged. The sample carrier (14) according to claim 17, wherein the first electrode is integrally connected to a third electrode disposed laterally adjacent to the first electrode on the substrate (20), and the second electrode is integrally connected to a fourth electrode is arranged laterally next to the second electrode on the substrate (20), so that an electrical measurement between the third and fourth electrode is possible. 19. Sample carrier (14) according to one of claims 13 to 18, wherein the heating tracks (20) are formed from a structured electrically conductive thin-film layer on the substrate (20). The system of any one of claims 13 to 19, wherein the substrate (20) of the sample carrier (14) is flexible.