EP2895268B1 - System zur durchführung einer berührungslosen messung an einer probe und probenträger - Google Patents
System zur durchführung einer berührungslosen messung an einer probe und probenträger Download PDFInfo
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- EP2895268B1 EP2895268B1 EP13783510.4A EP13783510A EP2895268B1 EP 2895268 B1 EP2895268 B1 EP 2895268B1 EP 13783510 A EP13783510 A EP 13783510A EP 2895268 B1 EP2895268 B1 EP 2895268B1
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- heating
- substrate
- sample
- electrode
- sample carrier
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L7/00—Heating or cooling apparatus; Heat insulating devices
- B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
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- H—ELECTRICITY
- H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
- H05B—ELECTRIC HEATING; ELECTRIC LIGHT SOURCES NOT OTHERWISE PROVIDED FOR; CIRCUIT ARRANGEMENTS FOR ELECTRIC LIGHT SOURCES, IN GENERAL
- H05B3/00—Ohmic-resistance heating
- H05B3/20—Heating elements having extended surface area substantially in a two-dimensional plane, e.g. plate-heater
- H05B3/22—Heating elements having extended surface area substantially in a two-dimensional plane, e.g. plate-heater non-flexible
- H05B3/26—Heating elements having extended surface area substantially in a two-dimensional plane, e.g. plate-heater non-flexible heating conductor mounted on insulating base
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0673—Handling of plugs of fluid surrounded by immiscible fluid
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/14—Process control and prevention of errors
- B01L2200/141—Preventing contamination, tampering
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0627—Sensor or part of a sensor is integrated
- B01L2300/0645—Electrodes
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/18—Means for temperature control
- B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
- B01L2300/1827—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using resistive heater
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- H—ELECTRICITY
- H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
- H05B—ELECTRIC HEATING; ELECTRIC LIGHT SOURCES NOT OTHERWISE PROVIDED FOR; CIRCUIT ARRANGEMENTS FOR ELECTRIC LIGHT SOURCES, IN GENERAL
- H05B2203/00—Aspects relating to Ohmic resistive heating covered by group H05B3/00
- H05B2203/002—Heaters using a particular layout for the resistive material or resistive elements
- H05B2203/007—Heaters using a particular layout for the resistive material or resistive elements using multiple electrically connected resistive elements or resistive zones
Definitions
- 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.
- ⁇ TAS Micro Total Analysis Systems
- 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, thus producing 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 represent different 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.
- a typical layout of a micro-heater is a thin metallic or doped Si layer 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 the 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 ).
- 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, Sensors and Actuators B, 2002, 84, 283-289 . JY 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 Micro Devices, 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.
- metal grids have been used as semi-transparent electrode materials to replace the commonly used ITO in the search for a cheaper 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
- the US 2011/0056926 A1 proposes to perform PCR studies a microfluidic device having heating elements in the form of thin-film resistors extending in a web shape along each of a microfluidic channel of the microfluidic device to be individually controllable.
- XP 11441122 discloses for carrying out PCR analyzes as a heating device a microscope glass slide with a resistance thin film, which is formed in the form of a serpentine extending between two electrodes.
- the WO 2009/019658 A2 discloses an integrated microfluidic device with multiple PCR chambers that are individually fillable and heated via a serpentine conductor.
- the US 2009/0211336 deals with so-called “preconcentrators” which are there to reversibly capture an analyte of interest, then to give it back to a detector in a so-called “desorption”. Therefore, the heating element is the US 2009/0211336 as an open grid to allow a fluidic medium with the analyte of interest to flow through the heating element to be trapped in the trapping phase by the heating element.
- the EP2314552 A1 discloses a heating element having a transparent substance, a conductive heating line, bus bars and a power section, wherein 30% or more of the entire area of the transparent substance has a conductive heating line structure in which, when the straight line intersecting the conductive heating line is pulled, a ratio of a standard deviation with respect to an average of distances between adjacent intersections of the straight line and the conductive heating line is 2% or more.
- the EP1972375 A1 discloses a microfluidic device having a two-dimensional array of components for processing a fluid and / or detecting properties of the fluid. Each component is coupled to at least one control port, which allows an active matrix to individually change the state of each component.
- the components comprise at least one heating element.
- the active matrix comprises a two-dimensional array of electronic components realized in thin film technology on a flexible substrate, this provides a high adaptability of the device.
- 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.
- a sample carrier 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.
- the heating paths even form a two-dimensional lattice structure, isolated breaks and cross-sectional tapers of the heating lanes have a less negative effect on homogeneity of the sample heating over the heating region of the substrate covered by the heating lanes, since their occurrence in individual lugs of the two-dimensional lattice through the lattice structure or adjacent lattices Bars are bridged. It is thus possible to reduce the manufacturing tolerances in favor of lower manufacturing 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.
- 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.
- Fig. 1 shows a system 10 for performing a non-contact measurement on an example biological and / or chemical sample 12.
- the sample may be, for example, a liquid, such as a solution, a suspension or the like.
- sample 12 contains a particular analyte.
- sample 12 could also be a solid, such as a sediment.
- the aforementioned analyte may be atoms, molecules or other matter of any kind, such as biological cells, DNA, gene-antigen compounds, etc.
- the 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 very 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.
- heating paths 20 on the substrate a parallel connection between the heating terminals 16 and 18, so that the biological / chemical sample after application of the same on the sample carrier 14 by applying a voltage between the heating terminals 16 and 18th is heated.
- the system 10 further includes a measuring assembly 26 for performing a non-contact measurement on the biological / chemical sample 12 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 optical observation by 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.
- a measuring assembly 26 for performing a non-contact measurement on the biological / chemical sample 12 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 optical observation by 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.
- the sample 12 has been shown as if it were applied on the front side 22 or on the heating tracks 20, the application could also be carried out on the rear side 16 for performing the non-contact measurement. 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. You can see it in FIG. 2 the heating connections 16 and 18 and the heating tracks 20 therebetween.
- the heating tracks 20 form a two-dimensional lattice structure of printed-wire lattice segments 34 which meet at lattice nodes, and lattice interspaces or meshes 36 which are surrounded by lugs 34 which can not be further reduced and in which the lattice of heating lanes 20 expose the substrate 15.
- 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. You can see it in FIG. 2 the heating connections 16 and 18 and the heating tracks 20 therebetween.
- the heating tracks 20 form a two-dimensional lattice structure of printed-wire lattice segments 34 which meet at lattice nodes, and
- the grid interstices 36 are exemplified to be square, but, in alternative embodiments, could 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.
- the heating tracks 20 according to Fig. 2 may occur any interruptions of the heating paths 20, as exemplified in Fig. 2 at 38 in a web of the grid, or cross-sectional tapers of the heating tracks 20 are bridged in webs of the grid so that no adverse effects on the heating homogeneity over the heating area 32 or away the same are mitigated.
- FIG. 2 a sample carrier is shown 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, this laterally constant surface density need not necessarily be.
- Fig. 3 11 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.
- 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.
- Fig. 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 run in a straight line between the lattice nodes 40, but may also be laterally curved.
- Fig. 4b shows that the heating terminals 16 and 18 could be formed by electrodes which are arranged in opposite edge regions 42 and 44 of the example rectangular or cuboid substrate 15 on the rectangular front side 22. In other words, in the case of Fig. 4b the heating region 32 laterally between the heating connections 16 and 18. It can, as it is in Fig.
- Fig. 4b is illustrated to be elongated to extend along its length between the heating ports 16 and 18 so that the latter are at both ends of the region 32.
- Fig. 4c shows an alternative in which the heating region 32 is elongate but bent along its length to extend non-rectilinearly like a web across the front surface 22, across the web width and web length of the region 32 that formed by the heating webs 20 Grating extends from a heating connection 16 to the other heating connection 18.
- 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 in this example.
- FIG. 12 also shows that the front surface 22 of the substrate 15 need not necessarily be completely exposed to 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.
- 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.
- 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.
- the example of Fig. 4e is of course combinable with the example of FIG. 4d, ie it may also be provided the protective layer 22 for covering the heating tracks 20, wherein the protective layer may 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 it is a preferably transparent to the light of the optical measuring system substrate of a transparent material, such as glass or the like.
- 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 it is in Fig. 2 is still shown as an example, for carrying out a four-point measurement of the sample carrier in addition also electrodes 50 and 52, which are integrally formed with the electrodes 16 and 18, respectively.
- An in Fig. 2 A dashed line 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 tracks 20.
- the readout circuit could be part of the system of Fig. 1 be.
- Fig. 5 shows by way of example the sequence of a method for carrying out a non-contact measurement in a sample.
- a step 56 one of the sample carriers described above is provided.
- the sample is applied to the sample carrier.
- the application may be on the front side 22 or on the rear side 24, but each overlap laterally with the heating region 32.
- 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.
- one step 62 is then performed in the heated state of the sample, the non-contact measurement on the same.
- the above embodiments have shown examples of a sample carrier that could serve as a heating element in biological or chemical applications.
- material for the heating tracks 20 metal could be used.
- 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 type of regular polygon .
- 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.
- a meandering heater has a more circular hot spot when heated, while a mesh has a more rectangular shape, which means that the net dissipates heat more efficiently relative to its own heater surface than a meandering heater.
- a mesh has a more rectangular shape, which means that the net dissipates heat more efficiently relative to its own heater surface than a meandering heater.
- a larger surface area can be uniformly heated.
- Fig. 6a shows a meandering heater with 15 ⁇ m line / heating track and 150 ⁇ m space on a PEN film substrate
- Fig. 6b shows its corresponding heat profile in a substrate on the thermochromic liquid crystal layer at 62 ° C.
- the heater surface is 1.5 x 3 mm 2 .
- Fig. 7a shows a network heating device or a sample carrier with 15 microns line / heating path and 150 microns 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 you can see, the heat is distributed in the case of Fig. 7b even.
- the heat distribution on the overall heater surface can be further improved using the array of gradually varying size geometries as in FIG Fig. 3 where heat losses at the periphery of the heater can be compensated by increasing the number of heating pipes.
- a heating device can be manufactured on a substrate with low thermal conductivity, such as glass or polymer, in only one metallization step; ie no additional heat spreading layer which increases manufacturing costs and limits transparency is needed.
- Fig. 8a shows in comparison with Fig. 7a a network heating device with 5 micron line and 50 micron space on a PEN film substrate and Fig. 8b 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 .
- one or more metal layers eg vapor-deposited or sputtered
- one or more very thin layers will be sufficient to achieve the adequate resistance. This is particularly advantageous for samples where the heating device 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.
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Description
Die vorliegende Erfindung bezieht sich auf berührungslosen Messungen an Proben bzw. Probenmaterialien, wie z.B. biologischen und/oder chemischen Proben, Systeme für solche Messungen sowie Probenträger, die für solche Systeme geeignet sind.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.
Es wird davon ausgegangen, dass µTAS (Micro Total Analysis Systems = Mikrogesamtanalysensysteme) oder Lab-on-Chips in Bereichen, wie z.B. globaler Gesundheits- und Medizinforschung, eine wichtige Rolle spielen werden. Sie reduzieren Kosten und Zeit für Tests und Analysen. Die Beschränkung, dass dieselben Einwegartikel sind, die Materialauswahl, der Entwurf und die Herstellung sind alles Aspekte, die berücksichtigt werden müssen, um die Chipkosten niedrig zu halten und somit ein Bauelement mit Marktfähigkeit zu produzieren. Zahlreiche biologische und chemische Untersuchungen sind temperaturabhängig, wie z.B. PCR (Polymerase Chain Reaction = Polymerase-Kettenreaktion) und MCA (Melting Curve Analysis = Schmelzkurvenanalyse). Wenn eine solche Untersuchung auf Mikrogröße herunterskaliert wird, werden eine präzise Temperatursteuerung und eine thermische Homogenität integrierter miniaturisierter Erwärmungs- und Erfassungselemente in mikrofluidischen Merkmalen zu kritischen Faktoren für ein funktionsfähiges Bauelement.It is believed that μTAS (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, thus producing 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.
Mikroerwärmungsvorrichtungen sind allgegenwärtig in verschiedenen MEMS- und mikrofluidischen Bauelementen. Letztere stellen verschiedene Funktionen in physikalischen oder chemischen Sensoren (
Für biologische Anwendungen ermöglicht eine optische Transparenz des Substrats eine Online-Überwachung und -Beobachtung der Probe. Transparente Erwärmungselemente für Lab-on-Chip-Anwendungen wurden hergestellt durch Strukturieren von ITO (Indium-Tin-Oxide = Indiumzinnoxid) auf Glas (
Transparente Elektroden sind auch bei einem großen Bereich von optoelektronischen Bauelementen, wie z.B. organische LEDs, Fotovoltaikzellen und Flüssigkristallanzeigen, wesentliche Elemente, die zur Spannungserzeugung für die optoelektronische bzw. elektrooptische Wandlung dienen. In diesen Bereichen wurden Metallgitter als halbtransparente Elektrodenmaterialien verwendet, um auf der Suche nach einem günstigeren Elektrodenmaterial das üblicherweise verwendete ITO zu ersetzen (
Wie im Vorhergehenden erwähnt, gibt es bereits Probenträger, bei denen eine Heizbahn mäanderförmig auf einem Substrat gebildet ist. Das Problem bei diesen Probenträgern besteht allerdings darin, dass eine Unterbrechung der Leiterbahn für die Erwärmungsvorrichtung unweigerlich zur Folge hätte, dass letztere ihre Funktion verliert. Dies erhöht den Herstellungsaufwand, denn entweder müssen bei der Herstellung Abmessungen, Materialauftrag usw. mit mehr Sicherheitsabständen zu ansonsten möglichen Grenzwerten eingestellt werden, oder die Produktion muss aufwendig überwacht werden, was wiederum dem Ziel nach möglichst geringen Herstellungskosten entgegensteht. Ein weiterer Nachteil einer mäanderförmigen Führung der Heizbahn über das Substrat des Probenträgers hinweg besteht in der inhärent auftretenden Flächendichteerhöhung an denjenigen Rändern des Substrates, an denen die Mäanderform ihre Schleifenumkehrpunkte aufweist.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. Another 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.
Die
Die XP 11441122 offenbart zur Durchführung von PCR-Analysen als Heizvorrichtung einen Mikroskopglasprobenträger mit einem Widerstandsdünnfilm, der in Form einer Serpentine gebildet ist, die sich zwischen zwei Elektroden erstreckt.XP 11441122 discloses for carrying out PCR analyzes as a heating device a microscope glass slide with a resistance thin film, which is formed in the form of a serpentine extending between two electrodes.
Die
Die
Die
Die
Die Aufgabe der vorliegenden Erfindung besteht deshalb darin, ein System und ein Verfahren zur Durchführung einer berührungslosen Messung einer Probe sowie einen Probenträger mit verbesserten Charakteristika zu schaffen.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.
Diese Aufgabe wird durch die Gegenstände der unabhängigen Patentansprüche gelöst.This object is solved by the subject matters of the independent claims.
Gemäß einem ersten Aspekt der vorliegenden Erfindung wird bei einer Durchführung einer berührungslosen Messung an einer Probe ein Probenträger verwendet, bei dem die Heizbahnen auf dem Substrat eine Parallelschaltung zwischen dem ersten und dem zweiten Heizabschluss bilden, so dass, wenn durch Anlegen einer Spannung zwischen dem ersten und dem zweiten Heizanschluss eine auf dem Probenträger aufgebrachte Probe erwärmt wird, die Erwärmungseigenschaften des Probenträgers auch dann nicht beeinträchtigt werden, wenn einzelne Unterbrechungen der Heizbahnen aufgrund von beispielsweise Prozessschwankungen bei der Herstellung der Heizbahnen vorhanden sind.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.
Bilden die Heizbahnen sogar eine zweidimensionale Gitterstruktur, so wirken sich vereinzelte Unterbrechungen und Querschnittverjüngungen der Heizbahnen weniger negativ auf eine Homogenität der Probenerwärmung über die durch die Heizbahnen abgedeckte Erwärmungsregion des Substrats aus, da deren Auftreten in einzelnen Stegen des zweidimensionalen Gitters durch die Gitterstruktur bzw. benachbarte Stege überbrückt werden. Es ist also möglich, die Herstellungstoleranzen zu Gunsten geringerer Herstellungskosten zu reduzieren. Ferner ist es möglich, die Heizbahnen optisch intransparent auszuführen, und dennoch eine Semitransparenz des Probenträgers bei eventuell vorhandener Transparenz des Substrats beizubehalten, da die Gitterzwischenräume beziehungsweise Maschen des zweidimensionalen Gitters die Transparenz des Substrats in Dickerichtung des Substrats bewahren.If the heating paths even form a two-dimensional lattice structure, isolated breaks and cross-sectional tapers of the heating lanes have a less negative effect on homogeneity of the sample heating over the heating region of the substrate covered by the heating lanes, since their occurrence in individual lugs of the two-dimensional lattice through the lattice structure or adjacent lattices Bars are bridged. It is thus possible to reduce the manufacturing tolerances in favor of lower manufacturing 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.
Gemäß einem Ausführungsbeispiel werden die Heizbahnen derart angeordnet, dass die Flächendichte der Heizbahnen von einer Flächenmitte des Substrats nach außen hin zunimmt. Auf diese Weise ist es möglich, die ansonsten häufig
auftretenden Inhomogenitäten des Erwärmungsprofils über das Substrat hinweg, wonach meistens die Erwärmung am Rand des Substrats hin abnimmt, zu vermeiden.According to an exemplary embodiment, 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.
Weitere bevorzugte Ausführungsbeispiele der vorliegenden Erfindung sind Gegenstand der abhängigen Patentansprüche. Beispiele für weitere Aspekte sind in den Abbildungen dargestellt, unter welchen
- Fig. 1
- eine schematische Zeichnung eines Systems zur Durchführung einer berührungslosen Messung an einer Probe;
- Fig. 2
- eine schematische Draufsicht auf einen Probenträger gemäß einem Ausführungsbeispiel;
- Fig. 3
- eine schematische Draufsicht auf einen Probenträger gemäß einem alternativen Ausführungsbeispiel mit nach außen hin zunehmender Heizbahnendichte;
- Fig. 4a
- eine schematische Draufsicht auf einen Probenträger mit nicht-geradlinigen Gitterstegen;
- Fig. 4b
- eine schematische Draufsicht auf einen Probenträger 14 unter vollständiger Darstellung der Substratvorderseite;
- Fig. 4c
- eine schematische Draufsicht auf einen Probenträger mit nicht-geradliniger Erstreckung des Heizbahngitternetzes;
- Fig. 4d
- eine schematische Seitenschnittansicht eines Probenträgers bei welchem eine Schutzschicht die Heizbahnen abdeckt;
- Fig. 4e
- eine schematische Raumansicht eines Probenträgers bei welchem die mit den Heizbahnen versehene Seite des Substrats zusammen mit einem Deckelelement zumindest einen Kanal oder eine Kammer bildet, an den bzw. die der Erwärmungsbereich angrenzt;
- Fig. 5
- ein Flussdiagramm eines Verfahrens zur Durchführung einer berührungslosen Messung an einer Probe;
- Fig. 6a und 6b
- eine schematische Draufsicht und eine dazugehörige Erwärmungsverteilung eines Probenträgers mit einer mäanderförmig geführten Heizbahn;
- Fig. 7a und 7b
- eine schematische Draufsicht und eine dazugehörige Erwärmungsverteilung eines Probenträgers mit exemplarisch quadratischen Maschen im Heizbahngitternetz; und
- Fig. 8a und 8b
- eine schematische Draufsicht und eine dazugehörige Erwärmungsverteilung eines Probenträgers mit engmaschigeren quadratischen Heizbahngitternetzen als
Fig. 7a und 7b zeigt.
- Fig. 1
- a schematic drawing of a system for performing a non-contact measurement on a sample;
- Fig. 2
- a schematic plan view of a sample carrier according to an embodiment;
- Fig. 3
- a schematic plan view of a sample carrier according to an alternative embodiment with outwardly increasing heating track density;
- Fig. 4a
- a schematic plan view of a sample carrier with non-linear grid bars;
- Fig. 4b
- a schematic plan view of a sample carrier 14 with complete representation of the substrate front side;
- Fig. 4c
- a schematic plan view of a sample carrier with non-linear extension of the Heizbahngitternetzes;
- Fig. 4d
- a schematic side sectional view of a sample carrier in which a protective layer covers the heating tracks;
- Fig. 4e
- a schematic space view of a sample carrier in which the side of the substrate provided with the heating tracks forms together with a cover element at least one channel or chamber, to which the heating region adjacent;
- Fig. 5
- a flowchart of a method for performing a non-contact measurement on a sample;
- Fig. 6a and 6b
- a schematic plan view and an associated heating distribution of a sample carrier with a meandering guided heating path;
- Fig. 7a and 7b
- a schematic plan view and an associated heating distribution of a sample carrier with exemplary square meshes in Heizbahngitternetz; and
- Fig. 8a and 8b
- a schematic plan view and an associated heating distribution of a sample carrier with close-meshed square Heizbahngitternetzen as
Fig. 7a and 7b shows.
Das System umfasst einen Probenträger 14 mit einem Substrat 15, einem ersten und einem zweiten Heizanschluss 16 und 18 sowie Heizbahnen 20. Die Heizbahnen 20 sind auf dem Substrat 15 angeordnet, wie zum Beispiel einer Vorderseite 22 desselben. Auf eben jener Vorderseite 22 können auch die Heizanschlüsse 16 und 18 angeordnet sein, wobei gemäß einer Alternative letztere aber auf einer der Vorderseite 22 abgewandten Rückseite 24 des Substrats 15 angeordnet sind oder auf einer Seitenfläche des Substrats 15.The system includes a sample carrier 14 having a
Wie es im Folgenden noch näher beschrieben werden wird, bilden die Heizbahnen 20 auf dem Substrat eine Parallelschaltung zwischen den Heizanschlüssen 16 und 18, so dass die biologische/chemische Probe nach Aufbringen derselben auf den Probenträger 14 durch Anlegen einer Spannung zwischen den Heizanschlüssen 16 und 18 erwärmbar ist.As will be described in more detail below, form the
Das System 10 umfasst ferner eine Messanordnung 26 zur Durchführung einer berührungslosen Messung an der biologischen/chemischen Probe 12. In
Es wird darauf hingewiesen, dass, obwohl in
Dadurch, dass die Heizbahnen 20 gemäß
Während in
In den nachfolgend kurz beschriebenen Figuren sind verschiedene weitere Varianten exemplarisch dargestellt.
Bei dem Substrat 15 von
In anderen Worten ausgedrückt, zeigten obige Ausführungen Beispiele für einen Probenträger, der als Erwärmungselement bei biologischen bzw. chemischen Anwendungen dienen könnte. Als Material für die Heizbahnen 20 könnte Metall verwendet werden. In dem Fall der Ausführung in Form eines Netzes bildete dann die Metallnetzstruktur ein Array von regelmäßigen oder allmählich in der Größe variierenden Öffnungen 36 in der Form von beispielsweise Quadraten oder Rechtecken, wie es im Vorhergehenden gezeigt wurde, oder von Kreisen oder jeglicher Art von regelmäßigen Polygonen. Die Heizbahnen könnten insbesondere aus einer elektrisch leitenden Dünnfilmschicht gebildet sein, wie zum Beispiel durch Strukturierung derselben. Die Dünnfilmschicht könnte auf das beispielsweise transparente, starre oder flexible Substrat 15 auf unterschiedliche Weise aufgebracht sein. Auch die Strukturierung kann auf unterschiedliche Art erfolgen.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
Die Anwendungen obiger Ausführungsbeispiele umfassen Proben in der Biologie oder Chemie. Biologische Anwendungen, wie z.B. Proteomik, Genetik und Zellenproben sowie Bioreaktoren mit dem Bedarf an Erwärmung und optischer Transparenz können in Betracht gezogen werden. Andere Anwendungen können Hydrogels und andere Polymersysteme sein, die Temperatursteuerung benötigen.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.
Im Vergleich zu herkömmlichen Einzeldrahterwärmungstechnologien besitzen obige Ausführungsbeispiele, die eine Netzstruktur aus Heizbahnen verwenden, folgende Vorteile:
- Eine Netzstruktur stellt eine höhere Herstellungsrobustheit dar im Vergleich zu einem/einer Mäander/Serpentine. Falls eine Unterbrechung eines Leiters in einem Mäander auftreten würde, würde die Erwärmungsvorrichtung beziehungsweise der Probenträger ihre/seine Funktion verlieren, während eine Netzerwärmungsvorrichtungsstruktur nach wie vor funktionieren würde, da die elektrische Leitung anstatt nur über einen über mehrere Leiter beziehungsweise
Stege 32 verteilt ist. Außerdem ist die Netzerwärmungsvorrichtung toleranter in Bezug auf die Kompensation von Abweichungen von der Entwurfsgeometrie des Leiters. Beispielsweise führen Leiterbeschränkungen aufgrund von Ätzdefekten zu lokalen hohen Widerständen und heißen Punkten in einer Mäanderstruktur. Die Netzstruktur versucht stattdessen die Quelle der Nicht-Einheitlichkeit zu kompensieren, indem sie Strom von den Hochwiderstandsbereichen weg leitet.
- A mesh 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.
Eine Mäandererwärmungsvorrichtung hat einen kreisförmigeren heißen Punkt (hot spot), wenn dieselbe erwärmt ist, während ein Netz einen eher rechteckigen aufweist, was bedeutet, dass das Netz die Wärme effizienter ausbreitet relativ zu ihrer eigenen Erwärmungsvorrichtungsoberfläche als eine Mäandererwärmungsvorrichtung. Folglich kann unter Verwendung eines Netzes eine größere Oberfläche einheitlich erwärmt werden. Vergleiche beispielsweise
Die Wärmeverteilung auf der Gesamterwärmungsvorrichtungsoberfläche kann weiter verbessert werden unter Verwendung des Arrays von Geometrien mit allmählich variierender Größe wie in
Durch Reduzieren der Netzgröße (dünnere Leitungen beziehungsweise Stege 32 und kleinere Öffnungen beziehungsweise Maschen 32) kann thermische Homogenität auf der Mikroskala (definiert durch Abmessungen, die viel geringer sind als die Substratdicke) erreicht werden (vgl.
Falls eine oder mehrere Metallschichten (z.B. aufgedampft oder gesputtert) zur Bildung der Bahnen 20 verwendet wird, ist/sind eine oder mehrere sehr dünne Schichten ausreichend, um die angemessene Widerstandsfähigkeit zu erreichen. Dies ist besonders vorteilhaft für Proben, wo die Erwärmungsvorrichtungstopografie eine weitere Verarbeitung stört, oder, wenn dieselbe in fluidische Strukturen integriert ist, Flusscharakteristika in Kanälen stören könnte, wie z.B. in dem Fall von
Die Heizbahnen müssen nicht aus ITO gebildet sein, was teuer ist. Das fördert folglich eine kostengünstige Herstellung, die für Diagnoseprodukte wesentlich ist.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.
Ein Netz hat eine geringere Widerstandsfähigkeit als ein Mäander. Daher muss für eine gegebene Erwärmungsleistung an das Netz weniger Spannung angelegt werden als an eine Mäandererwärmungsvorrichtung. Dies ist ein Vorteil für Systeme mit niedrigen Versorgungsspannungen, insbesondere batteriebetriebene tragbare Vorrichtungen.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.
Weitere Alternativen zu obigen Ausführungsbeispielen wären natürlich denkbar.Other alternatives to the above embodiments would of course be conceivable.
Claims (9)
- Sample carrier (14) for a sample for performing contactless measurement on the sample, comprising:a substrate (15) in the form of a transparent PEN foil substrate;first and second heating terminals (16, 18) on a front of the substrate; andheating traces (20) arranged on the front of the substrate and forming a parallel connection between the first and second heating terminals (16, 18) in that the heating traces (20) form a two-dimensional grid structure extending between the first and second terminals,wherein the first and second heating terminals (16, 18) are formed by first and second electrodes,wherein the first and second electrodes are arranged in opposing edge regions of the substrate (15),wherein the first electrode is integrally connected to a third electrode arranged laterally adjacent to the first electrode on the substrate (15), and the second electrode is integrally connected to a fourth electrode arranged laterally adjacent to the second electrode on the substrate (15), such that electric measurement between the third and fourth electrodes is possible.
- Sample carrier (14) according to claim 1, wherein the heating traces (20) are arranged such that an area density of the heating traces (20) increases from a center of the area of the substrate towards the outside.
- Sample carrier (14) according to claim 1 or 2,
wherein the two-dimensional grid structure comprises an arrangement of grid spacings (36) having the same shape out of a square, rectangular or circular shape. - Sample carrier (14) according to one of claims 1 to 3,
wherein the heating traces (20) are formed of a structured electrically conductive thin-film layer on the substrate (15). - Sample carrier (14) according to one of claims 1 to 4,
wherein the substrate (15) of the sample carrier (14) is flexible. - Sample carrier (14) according to claim 1,
wherein the two-dimensional grid structure forms a regular grid, wherein an area density of the heating traces (20) is laterally constant. - System for performing contactless measurement on a sample, comprising:a sample carrier (14) for a sample for performing contactless measurement on the sample according to claim 1;a measurement arrangement (26) for performing contactless measurement on the sample,wherein the system further comprises a controller and a readout circuit,wherein the controller is implemented to apply a voltage for a heating current through the heating traces (20) via the first and second electrodes (A, B),wherein the readout circuit is implemented to sense, via the third and fourth electrodes, a sensor value which is a measure for a resistance of the heating traces (20).
- The system according to claim 7,
wherein the measurement arrangement (26) is configured to perform a measurement on the sample by means of light and the substrate (15) of the sample carrier (14) is transparent for the light. - Method for performing contactless measurement on a sample, comprising the steps of:providing a sample carrier (14) comprising:a substrate (15) in the form of a transparent PEN foil substrate;first and second heating terminals (16, 18) on a front of the substrate; andheating traces (20) arranged on the front of the substrate and forming a parallel connection between the first and second heating terminals (16, 18) in that the heating traces (20) form a two-dimensional grid structure extending between the first and second terminals,wherein the first and second heating terminals (16, 18) are formed by first and second electrodes,wherein the first and second electrodes are arranged in opposing edge regions of the substrate (15),wherein the first electrode is integrally connected to a third electrode arranged laterally adjacent to the first electrode on the substrate (15), and the second electrode is integrally connected to a fourth electrode arranged laterally adjacent to the second electrode on the substrate (15);depositing the sample on the sample carrier (14);heating the sample by applying a voltage between first and second heating terminals (16, 18); andperforming the contactless measurement on the sample and an electric measurement between the third and fourth electrodes.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102012219656.0A DE102012219656A1 (en) | 2012-10-26 | 2012-10-26 | SYSTEM FOR CARRYING OUT TOUCH-FREE MEASUREMENT ON A SAMPLE AND SAMPLE CARRIER |
PCT/EP2013/071952 WO2014064040A1 (en) | 2012-10-26 | 2013-10-21 | System for carrying out a contactless measurement on a sample and sample carrier |
Publications (3)
Publication Number | Publication Date |
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EP2895268A1 EP2895268A1 (en) | 2015-07-22 |
EP2895268B1 true EP2895268B1 (en) | 2017-03-29 |
EP2895268B8 EP2895268B8 (en) | 2017-08-02 |
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EP13783510.4A Not-in-force EP2895268B8 (en) | 2012-10-26 | 2013-10-21 | System zur durchführung einer berührungslosen messung an einer probe und probenträger |
Country Status (3)
Country | Link |
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EP (1) | EP2895268B8 (en) |
DE (1) | DE102012219656A1 (en) |
WO (1) | WO2014064040A1 (en) |
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DE102014221734A1 (en) | 2014-10-24 | 2016-04-28 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Measuring device and system for melting curve analysis of a DNA microarray, and use of a fluorescence detector array for analysis |
PT3100587T (en) | 2015-04-07 | 2020-10-12 | Cell Id Pte Ltd | A dc heater |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1498074A (en) * | 1975-03-10 | 1978-01-18 | Orbaiceta | Electric resistance heating devices |
GB2154403A (en) * | 1984-01-31 | 1985-09-04 | Glaverbel | Heatable glazing panels |
DE4019357C1 (en) * | 1990-06-18 | 1991-08-01 | G. Bopp & Co Ag, Zuerich, Ch | Flexible, electrically heatable, transparent panel - has heating grid embedded in sheet of thermoplastic material suitable for rear window of convertible car |
FR2765967B1 (en) * | 1997-07-11 | 1999-08-20 | Commissariat Energie Atomique | CHIP ANALYSIS DEVICE COMPRISING LOCALIZED HEATING ELECTRODES |
IL147227A0 (en) * | 1999-07-02 | 2002-08-14 | Clondiag Chip Tech Gmbh | Microchip matrix device for duplicating and characterizing nucleic acids |
DE102006045514B4 (en) * | 2006-08-16 | 2012-04-05 | Saint-Gobain Sekurit Deutschland Gmbh & Co. Kg | Transparent surface electrode |
US20080199861A1 (en) * | 2007-02-15 | 2008-08-21 | Honeywell International, Inc. | Real-time microarray apparatus and methods related thereto |
WO2009019658A2 (en) * | 2007-08-09 | 2009-02-12 | Koninklijke Philips Electronics N.V. | Integrated microfluidic device with local temperature control |
US8380457B2 (en) * | 2007-08-29 | 2013-02-19 | Canon U.S. Life Sciences, Inc. | Microfluidic devices with integrated resistive heater electrodes including systems and methods for controlling and measuring the temperatures of such heater electrodes |
US8395086B2 (en) * | 2008-02-22 | 2013-03-12 | Qinetiq Limited | Heater device |
DE102009014757A1 (en) | 2009-03-27 | 2010-10-07 | Polyic Gmbh & Co. Kg | Electrical functional layer, manufacturing method and use thereof |
-
2012
- 2012-10-26 DE DE102012219656.0A patent/DE102012219656A1/en not_active Withdrawn
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2013
- 2013-10-21 WO PCT/EP2013/071952 patent/WO2014064040A1/en active Application Filing
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DE102012219656A1 (en) | 2014-04-30 |
EP2895268A1 (en) | 2015-07-22 |
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