• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    The invention relates to a measuring arrangement (1) for the quantitative optical evaluation of a chemical reaction, comprising a sample carrier (2) with a carrier layer (3) and a sample layer (4) with an analysis side (8) and opposite a light exit side (14), a photosensitive sensor (5) with a plurality of photodetectors (6) on a support body and with a transparent cover layer (7) arranged above it. On the analysis side (8) in a longitudinal direction of the sample layer (2) spaced from each other, a plurality of test sections (9) are arranged. The analysis side (8) is arranged on the carrier layer (3) such that the test sections (9) face a volume of a microfluidic device (10). The sample carrier (2) is detachably arranged in a receiving device (20) so that the light exit side (14) faces the photosensitive sensor (5) and the test sections (9) are arranged above the photodetectors (6). Further, the distance (11) between the test sections (9) and the photodetectors (6) is smaller than 700 μm.
    公开号:AT510750A1
    申请号:T2066/2010
    申请日:2010-12-14
    公开日:2012-06-15
    发明作者:
    申请人:Greiner Bio One Gmbh；
    IPC主号:
    专利说明:

    15:22:53 14-12-2010 5/44 «, *« «fl * V * * * * * *» * I * · * • # * * »* * * * * ·» ι * k # r * «*» * »» I * «·· -1 -
    The invention relates to a measuring arrangement for the quantitative optical evaluation of a chemical reaction,
    In the case of a chemical reaction, a color change or a change in the transmission may occur as the result of the reaction, and it is also possible that an emission of electromagnetic radiation occurs as a result of the chemical reaction. In the measuring method used here, a sample to be analyzed, which is mostly in liquid form, is moved past at least one test section within a microfluidic system, wherein a chemical reaction occurs in the presence of an analyte in the sample and a correspondingly corresponding reagent in the test section come, which manifests itself in a change in the transmittance of the test section or in the emission of electromagnetic radiation from the test section.
    To evaluate the reaction result, which is directly related to the quantitative presence of the analyte in the sample, it is known to detect the test section with a photosensitive sensor and to evaluate the temporal behavior of the detected optical signal. Since the optical effects to be evaluated often turn out to be very small, it is of particular importance if the optical detector has a high sensitivity in order to achieve the largest possible signal-to-noise ratio (SNR), which in turn immediately minimizes the effect Detection threshold (LOD). In known evaluation devices, a photodiode array is arranged in front of the test section, wherein a test section is detected by a plurality of photodetectors, for example 5 to 7 photodetectors. However, this has the disadvantage that the amount attributable to each individual photodetector electromagnetic radiation is reduced and thus the incident or detected signal is often only slightly larger than the inevitable noise inherent in the photodetector, thus resulting in a very small SNR. In any case, to achieve the highest possible resolution with a very low detection threshold, it is disadvantageous if the signal N2010 / 24400 14/12 2010 DI 15:20 ISE / FM NR 77751 00 005 15:23:08 14-12- 2010 6/44 -2 of a test section is split over several photodetectors. Furthermore, it is likewise disadvantageous if the optical response, a change in the transmittance or a luminescence, occurs due to scattering effects on adjacent photodetectors which are not causally associated with the relevant test section.
    The object of the invention is therefore to provide a measuring arrangement in which the signal-to-noise ratio is improved over the prior art and thus a lower detection minimum is achieved.
    The object of the invention is achieved in that in a measuring arrangement with a sample carrier and a photosensitive sense »'the distance between the arranged on a sample layer of the sample holder test sections and the photodetectors, less than 700 gm. The sample carrier has a carrier layer and a Probenfage, further wherein the carrier layer has a discharge section, which is connected via a microfluidic with a reservoir The sample days has an AnaJyseseite and this opposite, a light exit side, wherein on the analysis side in a longitudinal direction of the sample layer from each other spaced, a plurality of test sections are angsordnet and further wherein the sample layer is arranged with the analysis side on the support layer such that the test sections are facing a volume of the microfluidic. This arrangement has the advantage that the Testabschnrtte come into contact with the sample material transported in the microfluidics, in particular a liquid sample material, and thus the chemical reaction can take place.
    The sample material is thereby applied in the delivery section, brought over the microfluidics past the test sections to a reservoir. In particular, the reservoir is large enough to receive the total amount of samples or reagents required for carrying out the measurement, in particular to pick it up securely, so that contact of the operator with the sample material is essentially not possible.
    The photosensitive sensor has a plurality of photodetectors on a support body, wherein a transparent cover layer is arranged above the photodetectors. The transparent cover layer is now designed such that reliable protection of the individual photodetectors is ensured, but the layer is sufficiently thin to achieve the training according to the invention and nevertheless has sufficient resistance to solvents or cleaning agents, since the photosensitive sensor in particular cyclically 0/24400 14/12 2010 DI 15:20 [SE / EM NR 7775] @ 006 15:23:26 14-12-2010 7/44 -3 personal with sample remains reliable too prevent. The cover layer may be formed, for example, as an epoxy resin.
    Since the sample carrier is detachably arranged in a receiving device of the sensor, so that the light exit side faces the photosensitive sensor and the test sections are arranged above the photodetectors, the sample carrier, in particular a disposable sample carrier, can be easily inserted into the measuring arrangement, the measurement of the chemical reaction being carried out and the sample carrier is subsequently removed from the measuring arrangement and disposed of
    According to a development, it is provided that the thickness of the cover layer is less than 500 pm. A reduction of the thickness of the cover layer to this value has the advantage over the photosensitive sensors known from the prior art, in which the thickness is mostly greater than 1000 pm, that a clear approach of the test section to the photosensitive sensor is made possible without the mechanical Protecting the individual photodetectors or affect the electrical contact of the photodetectors.
    To achieve the object of the invention, it is also advantageous if the thickness of the sample layer is less than 200 pm, since the distance between the test section and the photosensitive sensor is thus reduced, which directly affects more light on the photodetector or a smaller spread , The sample layer is, for example, formed from polystyrene, COC (cyclo-olefin copolymers).
    Based on the investigations that led to the measuring arrangement according to the invention, it has proved advantageous if the photosensitive sensor has at least 32 photodetectors, as this results in an optimal SNR and a very low detection threshold for standard laboratory sample carriers (173), the photosensitive sensor a modified Standardbauteii can be formed. The use of standard components has the particular advantage that the cost of the measuring arrangement can be kept low and thus a high acceptance among users can be found. With this design, it is advantageous if, furthermore, a test section has a dimension in the range of (0.5-1.5 mm) x (2 -4 mm), wherein a dimension of 1 x 2 mm is preferred
    In order to achieve the object according to the invention, it is also advantageous if the distance between two adjacent photodetectors is less than 150 μm, since the fraction N2010 / 24400 14/12 2010 DI 15:20 [SE / EM NR 77751 121007 15:23: 43 14-12-2010 8/44 -4-an unused area of the photosensitive sensor is reduced. In the case of a transmission measurement or an emission measurement, as far as possible, a continuous, photo-sensitive section should be present in order not to lose light, which does not fall on an area occupied by the photodetector, for the evaluation. The smaller the distance between the photodetectors, the more light falls on them and therefore the detected intensity and thus the SNR are increased.
    To achieve the object of the invention, it is advantageous if as much light as possible falls from the direction of a test section onto a photosensitive sensor assigned to the respective test section. Due to the given intensity distribution, which will mostly be a Gaussian distribution, however, it is advantageous according to a development if at least 99.5% of the electromagnetic radiation incident on the photosensitive sensor is distributed over a maximum of three photodetectors. Thus, it is ensured that the vast majority of the light intensity is incident on a single sensor and that only a very small edge edge joins the two adjacent photodetectors.
    In order to increase the measurements which can be carried out simultaneously, it is advantageous if, according to a development, the photosensitive sensor has at least two rows of photodetectors arranged next to one another at a distance from one another. In the case of a sample carrier with a correspondingly designed microfluidic device, twice the number of reaction measurements can thus be carried out simultaneously, which entails an increased throughput. In particular, a row-like or strip-like propagation of the photodetectors is preferred since it is advantageous for microfluidics if a channel which is as straight as possible is formed and thus the test sections and thus also the photodetectors are arranged in the longitudinal direction of the channel.
    According to a further development, the channel of the microfluidics arranged above the photodiode has a length of 30-50 mm, a width of 1-4 mm and a height of 10-200 μm, which on the one hand has the advantage that this channel or this microfluidics can be cost-effectively achieved Injection molding of the carrier layer can be produced. On the other hand, this channel has a very small volume, so that the consumption of sample chemistry or sample material is minimized, which in turn for the efficiency and the acceptance of the process is beneficial. Preferred is a design of the channel with a length of 40mm, a width of 2mm and a height of 100μιπ.
    Another advantage is a further development, according to which a pressure gradient with a resulting capillary force in N2010 / 24400 14/12 2010 DI 15:20 [SE / EM NR 77751 @ 008 15: 24-. 01 14-12-2010 9 M4 I «ft« * -5-
    Rlchtung the reservoir forms, since it is ensured that an independent passage of the sample through the channel or the microfluidic is ensured, so that in particular no means for generating a pressure difference or a flow movement is required. In particular, this involves a so-called convection-driven hybridization, in which convection gradient form in the channel, which in addition to the passage of the sample through the channel, also ensure a steering of the sample material towards the test sections.
    According to a development, the cover layer of the photodetector has a transparency maximum in the spectral range of 400 to 600 nm. The cover layer is preferably formed by an epoxy resin which has been influenced by additives, in particular by known dyes for plastics, in its spectral properties to the effect only in that, for chemiluminescence measurements preferred Spektraibereich, a transparency maximum. This ensures that light which does not originate from a chemiluminescent reaction does not pass through the covering layer or only passes strongly attenuated and thus has no or only a very small disturbing influence on the measurement result. In one development, the transparency maximum can be set by additives but also in another wavelength range, so as to be optimized, for example, for transmission measurements.
    Due to inaccuracies in the production of the sample carrier, in particular by slight deviation in the positioning, in particular when printing the test sections, as well as by slight deviations in the arrangement of the sample carrier in the receiving device, it can occur that a test section is not located exactly over a corresponding photodetector , Now, according to a development of the center distance between two adjacent test sections is greater than or equal to three times the center distance of the photodetectors, this has the advantage that, despite a non-exact alignment to no influence on the detection result, in particular that it has substantially no adverse effect on the signal-to-noise ratio and thus the measurement sensitivity is not affected. Furthermore, since the light emanating from the test section has a substantially Gaussian intensity distribution, the intensity maximum of the incident light can thus be inferred even in the case of inaccurate positioning, for example by means of interpolation taking into account the Gaussian distribution, as a result of which more signal components are included in the evaluation, which in turn is advantageous for the signal-to-noise ratio. In particular, the N201 (V24400 14/12 2010 DT 15:20 ISE / EM NK 7775) @ 009 15:24:20 14-12-2010 10/44 according to the invention is obtained in particular -6-
    Forming the measuring arrangement and the claimed distance of 3 mm positioning inaccuracy of +/- 0.45 mm, at a distance of 4 mm would receive a position inaccuracy of +/- 0.9 mmm. Thus, the measuring arrangement according to the invention for daily use is particularly suitable because possible positioning errors can be largely eliminated by the training according to further development.
    The solution of the object according to the invention can also be achieved by introducing more light onto the photosensitive sensor so that, according to a further development, the boundary surface of the channel opposite the photosensitive sensor is optically reflective. This reflection can be achieved for example by mirroring the boundary surface. However, it is also possible to apply a layer structure such that a refractive index jump occurs and incident light is directed back to the photosensitive sensor. For transmission measurements, it may be provided, for example, to form the lateral boundary walls of the channel in a reflective manner so as to ensure a directing of light onto the sample material while avoiding incident control light on the photosensitive sensor. However, it is also possible for the carrier layer to be optically reflective, for example by being formed from a white material which, in contrast to a transparent material, largely reflects the incident light back.
    A development according to which the channel has a concave cross-section aligned with the photosensitive sensor has the advantage that a concave cross-section functions as a converging lens or collecting mirror and thus light which reflects the test section In, which leaves the photosensitive sensor in the opposite direction, and in particular on the photosensitive sensor is focused. The concave surface therefore preferably be reflective or formed with a refractive index coating. But it is also possible that the channel has a concave profile in the longitudinal direction in sections. Both possible embodiments have the advantage that more stray light is directed to the photosensitive sensor and thus is available for the detection.
    Another possibility for increasing the light intensity on the fetusensitive sensor is that the light exit side at least partially has a Uchtlenkstruk-tur, which may be formed for example as an embossed structure with a sawtooth or triangular profile. This light-guiding structure is intended to prevent light which has passed or originates from the test section from penetrating into adjacent spatial sections. N2010 / 24400 14/12 2010 TUE 15:20 [SE / EM NR 7775] g | 0l0 15:24:38 14- 12-2010 11/44 25 is scattered and thus lost for intensity measurement at the associated photodetector, in which such light rays are directed back towards the associated photodetector. An embossed structure also has the advantage that, in the transition from the sample carrier, in particular from the sample layer, to the unavoidable air gap between the sample carrier and the photosensitive sensor, due to the different refractive indices, total reflection in the cover layer of the photosensitive sensor may occur can come parallel to the photodetectors. Due to the embossed structure, the angular relationships during the transition from the sample carrier to the sensor can be positively influenced in order to reduce the risk of total reflection as far as possible.
    A development also consists in that the sample layer is designed as an optical fiber plate. Such an optical fiber plate is formed by a plurality of optical fibers is arranged close to each other, wherein the front ends of the optical fibers form the analysis side or light exit side. The space between the individual fibers can be formed, for example, by a transparent hardening resin. Thus, light emanating from or passing through the test section is taken over by optical fibers and directed to the photodetector in a targeted manner, whereby detection and directional guidance of stray light is thus also possible. It is also possible that the ends of the optical fibers are formed as micro-optics, thus providing an improved collection effect or improved focusing and thus in turn an increase in the light intensity directed onto the photodetector. During the transition from the air gap into the cover layer, total reflection in the cover layer can occur, as a result of which the incident light is lost for detection. Therefore, the cover layer may be formed as such a fiber plate and ensures a targeted steering of the incident light on the photodetectors.
    The transition from the sample carrier to the photosensitive sensor will usually be a small air gap, wherein the transition from the sample carrier to the air gap and from the air gap to the photosensitive sensor, a jump in the refractive index, whereby it may be a total reflection and thereby a loss of the reflected Beams of light coming. According to a further development, it is provided that the sample layer at least in sections has a refractive index step profile in the direction of its thickness, wherein this profile is designed such that the refractive index difference between the light exit side of the sample days and the air gap is as small as possible, so as little light as possible by total reflection at this interface N2010 / 24400 14/12 2010 Tue 15:20 [SE / EMNN 77751 ® ° J1 15:24:57 14-12-2010 12/44 I * · ft *
    -8- rert and direct as much light in the direction of the photosensitive sensor. The step index profile in the direction of the thickness of the sample layer will be similar, ie have a plurality of small refractive index differences in order to direct as much light as possible from the test section to the light exit side. The refractive index step profile can be formed, for example, by the sample layer being formed by a plurality of densely arranged layers of a material, each with a specific refractive index, which changes slightly from layer to layer. It is also possible that a plurality of layers, each having a specific refractive index from the vapor phase are applied, so as to form the step profile.
    In the same direction is a development according to which the sample layer in the direction of its thickness at least partially has a refractive index gradient profile. A gradient profile provides a continuous adjustment of the refractive index of the sample layer to the air in the air gap and thus provides a particularly optimal guidance of the light from the test section to the photosensitive sensor. A gradient profile is preferably formed from the vapor phase, so that a constant course of the refractive index is formed. Since the effort for producing a specific refractive index profile is quite high, it is provided that such a refractive index profile is arranged at least in the section of the sample benogen, in which the applied test sections are also located.
    A further possibility for preventing a refractive index jump is that an immersion layer is applied on the light exit side of the sample layer or on the cover layer of the photosensitive sensor, whereby the air is displaced out of the gap between the sample layer and the sensor and thus a jump in the refractive index to the air or air . is prevented from the air on the cover layer. The immersion layer can be applied, for example, as an immersion oil, as is known from microscopy. Furthermore, it is possible that, for example, a depot is provided on the light exit side, which is activated when the sample carrier is inserted into the receiving device and thus applies the immersion material to the light exit side. This development has the advantage that no additional operator actions are required, which is particularly important for field deployment or for single use.
    When performing the sample analysis, it is usually necessary to document the measurement result. Therefore, it is advantageous if an identity or identification feature is arranged on the sample carrier, since a direct assignment of the read-out N2010 / 24400 14/12 2010 DI 15:20 [SF./EM NR 7775] El 012 15:25: 15 14-12-2010 13/44 - 9-
    Signal curve of the individual test sections can be taken in a measurement protocol. Furthermore, different sample carriers with different test sections can be used, so that, for example, an identifier or configuration data of the test sections can also be stored in the identification tag. The feature is preferably contactlessly readable and can be formed, for example, by a 1D or 2D code, but it is also possible to design it as a RFiD feature. For the modularization of the measuring arrangement according to the invention, a further development is possible according to which so-called energy directors are applied on the analysis side and / or on the side of the carrier layer facing the analysis side, which enable the sample position to be connected to the sample carrier by means of Uitraschallschweißung. This makes it possible to produce the carrier layer and Probeniaga separated from each other, in particular to provide a universal carrier layer, which is assembled with a plurality of specifically trained sample layers, in particular with specific test sections, to the measuring arrangement according to the invention.
    Since the radiation emitted by the test section is largely undirected, a refinement of VorteH for which the sample layer and / or the carrier layer are formed as an optical polarizer is for a fluorescence measurement. If the light incident on the test section is polarized, the incident light can be masked out by an orthogonal polarization direction of the sample layer such that only the light emitted by the test section will be incident on the photodetector. A polarization assembly consists of two polarizing components known by the terms polarizer and analyzer. According to the development of the invention, the sample layer forms the analyzer. The polarizer may be formed by the carrier layer, it is also possible that a lighting device is provided which has a polarizer, with which the individual test sections are illuminated. By suppressing the incoming excitation light as far as possible, even very small reaction products can be read clearly, which in turn lowers the LOD.
    The object of the invention is also achieved by a measuring device for the optical evaluation of a chemical reaction, soft measuring device having a measuring arrangement according to the invention, wherein the sensor is arranged in a base body and a cap between a measuring position and a feed and removal position is ver-swiveled. Since the light intensities are very low both in chemiluminescence measurements and in transmission measurements, it is important that the coverage
    N201O / 244QO 14/12 2010 DT 15:20 [SE / EM NR 7775] @ 013 25 «* 15:25:34 14-12-2010 14/44 I t · *** · * *» · «• * In the measuring position, the test carrier and a section of the base light-tightly seal against the environment light-tight, since it is ensured that no external light the measurement can influence. This seal can be formed, for example, by a groove-shaped contact section between the base body and cap. Furthermore, it is possible to provide an elastic seal surrounding the area to be closed, which is pressed against the base body by the covering cap in the measuring position and thus ensures the light-tight closure.
    In transmission measurements, the attenuation of the light passing through the test section caused by the chemical reaction is detected, so that according to a further development in the cover cap a lighting device is present, which directs its light in the direction of the test sections. The illumination device may, for example, be formed by a luminescence carrier and / or an LED arrangement. It is also advantageous if the position of the light output along the test section can be influenced in a targeted manner. If, for example, a specific pattern of light is emitted, it is possible to carry out a calibration of the photosensitive sensor, wherein impurities can be detected by the disturbance of the expected brightness distribution caused thereby. Preferred is an embodiment with four light-emitting diodes which are arranged such that the entire longitudinal extent of the photosensitive sensor can be illuminated.
    To expand the field of application of the measuring device according to the invention or for adaptation to different test sections, it is advantageous if the lighting device can selectively deliver light in a plurality of wavelengths in a controllable manner. For this purpose, the illumination device can have a plurality of luminous means, which in each case emit light in a different spectral range, or the illuminant can be made tunable and thus emit light in a specific spectral range. It is also advantageous if the illumination device is designed in such a way that light can be emitted along the longitudinal extent of the photosensitive sensor at a plurality of positions, for example, in which a plurality of discrete illumination means are present, Thus, a specific illumination pattern or a specific intensity distribution on Photodetector to be created. For fluorescence measurements further refinement is advantageous, according to which the illumination device has a polarizer, wherein preferably the sample layer is designed as an analyzer. The polarization direction of the polarizer and of the analyzer are aligned normal to each other, which has the advantage that the polarized excite N2010 / 24400 14/12 2010 E 15:20 [SE / EM NR 77751 ®014 15:25:53 14-12- 2010 15/44 5 •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
    Since the delivery of various reagents may be required to carry out the measurement, a dispenser for reagents is arranged in the cap or in the main body. In this dispenser one or more reagents can be arranged in containers which together, selectively or before be applied to the sample carrier and consumed in carrying out the measurement.
    According to a development, the dispensing device has an actuating element and a depot for reagents, wherein the depot is preferably designed to be coupled. The actuating element may be formed, for example, by a push button or a perforation device and thus releases an optional amount of depot content or the intended content. A couplable depot has the advantage that a disposable system can be formed by this, whereafter the sample carrier and the depot are selected for carrying out the measurement and disposed of after the implementation. This is particularly advantageous for application safety, as the operator can always be sure to use the right reagents and not, as has hitherto been the case, to handle voluminous reservoirs for the requisite reagents, with the possibility of contamination recurrent. The coupling device can be formed, for example, by a membrane-needle combination, wherein the membrane seals a container of the sample dispensing device and when inserted by a hollow needle or a mandrel is pierced so as to provide the sample chemistry present in the container. In particular, the sample delivery device can be designed such that a multiple coupling is possible. A membrane would automatically close the access after removal of the needle. However, it is possible that a spring-biased cap is pressed by a removal mandrel and thus allows access to sample chemistry fn a further development, the depot may be formed by a blister in which in each closed chambers reagents are present. The chamber is provided with a seal, which is destroyed by the actuator, whereby the contents of the chamber is released. It is also possible that the actuating device has an anti-cancerous agent, which is operatively connected to the control module, for example. N2010 / 24400 14/12 2010 Dl 15:20 [SE / EM NR 7775] ®015 15:26:11 14-12- This can be formed by an electromagnetically or electromechanically actuated stamp, which releases the contents of the depot when activated. It is also advantageous if the blister is automatically moved by the actuating device, for example by means of a stepper motor, to automatically select the next required reagent for release. Thus, once again compliance with a required reagent input can be guaranteed.
    In order to ensure compliance with the order of the sample delivery can be provided that each depot is associated with an actuating element, wherein the actuating elements are provided with a sequence identifier. This may be provided, for example, by a color coding in the sense of a traffic light system, with regard to a disposable sample dispensing device, a mechanical locking or unlocking device may be provided, so that the operator must deliver the reagents in any case in the correct order. It is also advantageous for the application security if the control module is operatively connected to an outlet device of the sample delivery device, since a targeted delivery of the sample chemistry to the sample carrier, in particular to the delivery section or, if applicable, into the microfluidics, is possible. Since drainage chains may also have to be adhered to when carrying out the measurement, the control module can also be designed in such a way that the sample chemistry is dispensed from the sample delivery device into the delivery section of the sample carrier in a specific chronological sequence. The outlet device may be formed by a controllable valve, for example a solenoid valve, or a pulse-controlled dispensing device similar to that of an ink jet printer. In a further development, the flow through the outlet device can also be specifically adjusted, for example by a variable delivery opening.
    The previous developments have the particular advantage that the operating safety is increased by a sequence or a chronological order is maintained safely, in particular, provided that this delivery can take place with the cap closed, so that the light-tight completion of the sample carrier even at the addition of the sample chemistry is ensured. The cap or the meter may have externally accessible actuators to operate the sample dispenser accordingly. N2010 / 24400
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    In a development, it can be provided that the depot is arranged pivotably under the actuating element. For example, the depot may be a circular blister, which is inserted into the dispenser and is gradually pivoted, so that in any case the required order of reagent dispensing is met. For this purpose, the dispensing device or the depot may have a direction-giving structure which specifies a starting point and the direction of rotation. This can be formed, for example, by a starting knot and a sawtooth-like structure. It is also a strip-shaped design of the depot possible, with a start position and the progress direction can be fixed here,
    After inserting the sample carrier into the receiving device, for example, the microfluidics can be filled with a preparatory sample chemistry in order to prepare the test sections for the subsequent measurement. For this purpose, it is advantageous if the sample carrier is already inserted in the receiving device and in particular the cap is closed, so that according to a further development, the cap has a feed section, which contacts the delivery section of the sample carrier. This makes it possible to supply the sample chemistry or the sample to be analyzed from the outside, without having to handle the inserted sample carrier. Since the chemical reaction can be carried out quite quickly after addition of the sample to be analyzed, it is important if the sample holder is light-tight after the sample is dispensed, and if it is dispensed onto the sample holder with the cap open, there is always a risk of misoperation in dispensing the sample and the cap is not closed in time, so it can lead to a wrong measurement. With regard to a disposable use, the feed section can also be designed as a Bnwegvorrichtung and be disposed of after performing the measurement together with the sample carrier.
    Since an identification or identity feature can be arranged on the sample carrier, according to a development on the measuring device, a contactless acting triggering device is present. This read-out device can be formed, for example, by an optical 1D or 2D detection sensor or an RFID transmitting and receiving unit.
    In order to reduce the thickness of the air gap and thereby ensure a better coupling of the sample carrier to the photosensitive sensor is provided according to a development that in the cap, a pressure means for exerting a force on the sample carrier is arranged. This can be formed for example by an elastic material which exerts a force on the carrier layer and thus the sample position on N2010 / 24400 14/12 2010 DI 15:20 [SE / EM NR 7775] ®017 15:26:47 14-12 -2010 18/44 -14-the top layer of the photosensitive sensor presses. The elastic material may for example be formed by a foam material or by a spring-actuated biasing element.
    For a better understanding of the invention, this will be explained in more detail with reference to the following figures.
    Each shows in a highly schematically simplified representation:
    Fig. 1 is a sectional view of the measuring arrangement according to the invention;
    Fig. 2 a) A representation of the signal distribution of a test section on the photo-sensitive sensor. b) the measured dependence of the signal width on the photosensitive sensor, as a function of the distance between the test section and the photodetector;
    3 shows the number of illuminated photodetectors as a function of the distance between the test section and the photodetector;
    4 shows a representation of the intensity distribution on the photodetectors as a function of the center distance of the test sections;
    FIG. 5 shows an exposition of the measuring arrangement according to the invention; FIG.
    Fig. 6 a) A representation of an embodiment of the measuring device according to the invention; b) and c) Another possible embodiment of the measuring device according to the invention.
    By way of introduction, it should be noted that in the differently described embodiments the same Telle be provided with the same reference numerals and the same component names, the revelations contained in the entire description can be mutatis mutandis to the same parts with the same reference numerals or identical component names. Also, the location information chosen in the description, such as top, bottom, side, etc. related to the immediately described and presented figure and are to be transferred to the new situation in a change in position mutatis mutandis. Furthermore, individual features or combinations of features from the different exemplary embodiments shown and described can also represent independent, inventive or inventive solutions. N2010 / 24400 14/12 2010 Tue 15:20 [SE / EM NR 7775] 0018 5 15:27:01 14-12-2010 19/44 ····································································· * * * * * - 15- All information on value ranges in representational description should be understood to include any and all subsections thereof, eg the indication 1 to 10 should be understood to include all the parts ranging from the lower limit 1 and the upper limit 10, i. all subregions begin with a lower limit of 1 or greater and end at an upper limit of 10 or less, e.g. 1 to 1.7, or 3.2 to 8.1 or 5.5 to 10.
    Fig. 1 shows a Schnittdarsteliung the measuring device according to the invention, wherein the orders of magnitude for the representation of the features essential to the invention have been changed to an uneven scale. In particular, layer thicknesses or geometrical configurations are shown not to scale.
    The measuring arrangement 1 according to the invention has a sample carrier 2 with a carrier layer 3 and a sample layer 4. Further, a photosensitive sensor 5 is provided, which has a plurality of photodetectors 6, above which a transparent cover layer 7 is arranged. On a Anaiyseseite 8 of the sample layer 4 is spaced from each other arranged a plurality of test sections 9, the sample layer 4 is arranged with the analysis page 8 on the support layer 3 that the Testabschnrtte 9 are facing a volume of the microfluidic 10, in particular these arranged in the channel 23.
    The reaction of the sample material transported in the microfluidics 10 with the reagents in the respective test section 9 results in a change in the optical property or a chemiluminescence-based Uch-setting in the test sections 9, such that the photodetectors associated with the respective test section have a Change the incident light intensity. The advantage of the invention lies in the fact that the distance 11 between the test sections 9 and the photodetectors 6 is less than 700 pm. According to the invention, this is achieved, for example, by the thickness 12 of the cover layer 7 being less than 500 .mu.m and, furthermore, the thickness 13 of the sample layer 4 being less than 200 .mu.m.
    The transition from the light exit side 14 of the sample layer 4 to the cover layer 7 of the photosensitive sensor 5 can lead to refraction and scattering effects, which has the effect that the emission characteristic of the light emitted by the test section corresponds to a point light source. Therefore, the light of a test section 9 will not only fall on a photodetector 6 arranged directly underneath, but it will also expand, whereby the light emitted by the associated photodetector will also expand.
    N2010 / 2440Q 14/12 2010 Tue 15:20 [SE / EM NR 77751 @ 019 15:27:18 14-12-2010 20/44 5
    In addition, a radiation component will arrive. However, due to the formation of the distance 11 between the test sections 9 and the photodetectors 6 according to the invention, it is ensured that the majority of the radiation intensity only arrives at a photodetector, the majority of the radiation intensity being incident on a maximum of three photodetectors.
    Since the brightness signal to be detected often turns out to be very small and thus may be covered by the unavoidable inherent noise of each individual photodetector, it is of particular importance if the largest possible proportion of the radiation intensity emanating from a test section falls on a single photodetector or if the total Outgoing radiation intensity is limited to the smallest possible number of photodetectors. Only in this way can the largest possible signal-to-noise ratio or a lower lower detection limit be achieved. The support layer 3 is formed mostly transparent, for example, the test sections 9 opposite boundary surface 43 of the channel 23 may be formed optically reflective. However, it is also possible that the carrier layer 3 itself is formed optically reflective.
    In the course of investigations leading to the invention, it has been found that the signal distribution or the signal width on the photosensitive sensor gives information on how many strips on a photosensitive sensor with a dynamic range of> 100, ie a crosstalk (your 1% The most important parameter is the distance from test section to photodetector because the signal width is directly proportional to this distance The aim of the measurements was to get an overview of the distribution of the light signal from the test sections printed, for example, by a capillary printing method.
    The measurement resulted in a Gaussian distribution of the signal on the photosensitive sensor. A characteristic variable for a Gaussian curve is the 1 / e width, which is designated here by c. For such signals are within a width of 2 * c 04.2% of the signal. At a width on the 4 * c photosensitive sensor, 99.5% of the signal of a printed test step is distributed. Fig. 2a shows the typical signal distribution for a non-inventive test configuration of a slide with a printed test section (2x1 mm) on a 190pm thick sample layer over a photosensitive sensor, with the distance from the test section to the photodetectors being 1.54 mm. Here are 99.5% of the signal within 4 * c = 6.03 pixel. So let N2010 / 24400 14/12 20.10 Tue 15:20 [SE / EM NR 7775] @] 020 5 ► * * 15:27:36 14-12-2010 21/44 -17-estimate that in this Configuration can detect a maximum of 4-5 different strips with acceptable crosstalk and dynamic range.
    Measurements were made at a distance of 1.3.1.5, 2.5 and 3.5 mm between the photodetector test section. Applying the average {3 measured values) width of the detected signal (99.5%, ie 4 * c) on the photosensitive sensor to the distance between the test section and the sensor gives the dependency shown in FIG. 2b. So if you detect the brightness signal of a 1mm wide test section at a distance of 1.5mm (0.19mm film +1.35 mm glass to photosensitive tube (according to the sensor manufacturer)) 99.5% of the signal is distributed over 6 pixels. In this case you would have to print the test section with at least 6 pixel = 6 mm distance. In the preferred channel structure on a standard laboratory support (173M) with a channel length of 30 mm, a maximum of 5 bands could be detected if at least a dynamic range of 100 (ie a crosstalk <1%) should be covered.
    With this method, the possible number of detected test sections can be determined, as a result of these investigations one obtains the dependencies shown in FIG. Plotted over the distance 15 between the test section and the photodetector are two curves, a quasi-linear curve 16 and a substantially exponential curve 17 resulting from this curve. The quasi-linear curve 16 shows the dependence on which distance 15 between a test section and the photosensitive sensor, 99.5% of the total intensity of the light emitted by the test section, which number 18 of photodetectors is incident on. It can be seen from this diagram, for example, that at a distance of 1 mm between test section and photodetector, 99.5% of the total intensity strike almost 5 photodetectors. Dividing the channel length (ie 30 mm) by the '99.5%' width (in mm) of the bright signal of a single test section yields the second curve 17. This curve now indicates how many test sections 18 at which distance 15 between Test section and sensor are possible.
    Due to the preferred channel length of 30 mm, the desired measurement result was optimized so that at least eight test sections can be detected and evaluated with the detection device according to the invention. The shaded area indicates below which distance from test section to photodetector more than 8 strips can be detected. From the diagram, for eight strips, by analysis of curve 17, a value of about 0.7 mm is obtained. N2010 / 24400 14/12 2010 Tue 15:20 [SE / EM NR 7775] ®021 15:27:54 14-12-2010 22/44 I «· ··« II · * · · · · «« « * * * 1 · · · * * · '1 # ί »« * I «* * *» «·» * ·· * * · - 18- Ιη Fig. 4 shows the so-called signal crosstalk, ie how strong the brightness signal acts on the adjacent photodetectors due to its intensity distribution from one test section. In particular, here is the distance 19 between the test sections 9 of importance, because the greater this distance 19, the fewer signal components of a test section will fall into the detection range of each adjacent test sections and thus the associated photodetectors - assuming an equal distance between test section and photodetector. The situation in which each test section 9 emits a maximum brightness signal is shown in the lower diagram in each case in FIGS. 4a and 4b, with the usual intensity distribution of the brightness signal being shown in dashed lines 4b, this distance is 4 mm, so that only very small proportions of the radiation intensity of one test section act on adjacent test sections A small crosstalk is of particular importance in particular if very different intensity reactions occur in two adjacent test sections The limit range is given by the fact that the maximum brightness reaction takes place on one test section, the smallest possible detectable sample reaction takes place at the adjacent test section nd less than 700 pm between the test section and the photodetector, it is ensured in this case too that the brightness product of the intensive reaction does not cover that of the very weak reaction, and thus a clear separation of the two Reaktton products is possible.
    A large distance between the test sections has the further advantage that even inaccuracies which result when applying the test sections to the sample layer, for example when printing, as well as inaccuracies resulting from the insertion of the sample carrier in the receiving device, no or only a very small impact The detection characteristics, in particular on the signal-to-noise ratio, effect the lower detection limit and the crosstalk. In particular, this training yields a standard deviation of 1.5% at the determined concentration value, whereby the concentration value is practically independent of the positioning accuracy of the test sections or the arrangement in the recording device is. This design has the particular advantage that an application by unskilled personnel is thus possible, since alignment errors will essentially not affect the measurement result. N2010 / 24400 14/12 2010 Tue 15:20 [SE / EM NR 7775] @ 022 - 19- 15:28:13 14-12-2010 23/44 · * ·· · * &gt; »« · · · · · · ♦ · • I «1 · 1« ♦ ♦ 1 »« * · * · + «
    5 shows an exploded view of the measuring arrangement 1 according to the invention comprising the sample carrier 2 with the support layer 3 and the sample layer 4. The sample carrier 2 is detachably arranged in a receiving device 20 so that the light exit side 14 of the sample layer is arranged facing the photosensitive sensor 5. The photosensitive sensor 5 is in turn arranged in a main body 21, wherein the individual photodetectors 6 are covered by a transparent cover layer 7. On the analysis side 8 of the sample layer 4, a plurality of test sections 9 are arranged. The sample layer 4 is in turn arranged on the carrier layer, so that the test sections 9 face a volume of the microfluidic device 10, whereby, upon delivery of a sample to be analyzed at the delivery section 22, due to the geometrical characteristics of the channel 23, capillary movement of the analyte from the delivery section 22 through the channel 23 to a reservoir 24, comes. This also leads to a contact of the analyte with the test sections 9, which will lead to a chemical binding reaction in the respective test section, in the presence of a corresponding anion in the sample, leading to a change in the spectral properties or to a chemiluminescent one Light emission leads. With a channel length 25 of 30 mm for a standard Γ / 3 "sample carrier 2, the measuring arrangement according to the invention has been optimized so that eight test sections 9 of a total of 32 individual photodetectors 6 of the photosensitive sensor 5 are detected, so that 99.5% of the one test section assigned Brightness signal is detected by three photodetectors 6.
    The receiving device 20 is designed, for example, such that the sample carrier 2 is inserted into a fixed part of the receiving and is kept fixed by a second, movable and / or hinged part of the receiving device. It is also possible for a prestressed element to be arranged on one part of the receiving device, which is compressed when the sample carrier is inserted and thus fixes the sample carrier in the receiving device.
    6a shows a measuring device 26 according to the invention, comprising a measuring arrangement 1 in a base body 27, wherein a covering cap 28 is pivotably arranged about a pivot axis 29 between a measuring position and a feed and removal position 30.
    The photosensitive sensor 5 of the measuring arrangement 1 is preferably arranged in the main body 27, preferably such that the sample carrier 2 is held in the receiving device 20 such that the test sections along the channel 23 with its light exit side N2010 / 24400 14/12 2010 15:20 DI [SE / FM NR 77751 S] 023 15:28:32 14-12-2010 24/44 * * * * t * • * * * Μ · «« ♦ • · «· ·» · * «» * • i * t * * f * * * -20- are arranged above the photodetectors of the photosensitive sensor 5. For this purpose, the receiving device 20 can for example have a fixed and a longitudinally displaceable movable, spring-biased holding part, so that when inserting the sample carrier 2, the movable part can be moved in a longitudinal direction 31 to facilitate insertion of the sample carrier and this, after spring back into the Holding position, fixed accordingly. In addition to a longitudinally displaceable training but also a folding or snap mechanism can be provided. It is also possible that at least in one of the holding parts a pressure medium is present, for example, a rubber or spring element which, as described above, fixes the sample carrier after insertion.
    If the cover capa 28 is pivoted into the measuring position, the interior, in particular the sample carrier 2 and the photosensitive sensor 5, are sealed in a light-tight manner by a sealing element 32. The sealing element 32 may be formed for example by a tongue and groove connection, in the main body 27 may be provided to a circumferential groove-shaped recess into which a corresponding opposite spring of the cap 28, when pivoting the same in the measuring position, engages and closes the interior light-tight , However, the sealing element 32 may also be formed by an elastically deformable element, for example a foam material or a rubber seal, which in turn when closing the cap 28 due to a thereby caused compression of the sealing element 32 is a light-tight termination of the interior of the meter is given to the environment. The sample carrier 2 has a dispensing section 22, in which the sample to be analyzed is dispensed, which is automatically moved from the dispensing section 22 to the reservoir 24 due to the dimensioning of the channel 23 of the microfluidic device 10.
    However, the dispensing of sample material J at the delivery section 22 is problematic in that, on the one hand, the quantity to be dispensed is to be kept as precisely as possible, or an order of delivery of the sample chemistry must be observed. Furthermore, after the sample material has been dispensed by the passage of it past the test sections, the reaction and thus the change in the optical properties or the emission of light in the test sections occurs. If the cap 28 is not yet in the measuring position at this time, this can lead to incorrect measurements.
    FIGS. 6b and 6c show a further possible embodiment of the measuring device according to the invention, in which, for example, a supply device 34 can be provided in the cover cap, which supplies the delivery section 22 for liquid-tight delivery of the sample N2010 / 24400 14/12 2010 DI 15:20 [SE / EM NB 7775] @] 024 15:28:50 14-12-2010 25/44 5 4 t * I · «i * 4 · •» 4 4 4 * 4 * * «4 4 *« * * '* 44 444 * · 4 · 44 * 4 · '4 »*« 4 4 »** -21 -terials and also ensures the light-tight closure of the sample holder 2 from the environment. Thus, the sample carrier can be inserted into the receiving device 20 and then the cap 28 are closed without sample material or sample chemistry is already in the microfluidic 10, thereby ensuring that no chemical reaction is triggered in the test sections. Only then, with the cap closed and reliable production of a light-tight closure of the sample carrier, are the reagents or the sample to be analyzed delivered to the delivery device and forwarded by the latter to the delivery section 22 of the sample carrier 2. Since further reagents may additionally be required for carrying out the sample analysis, the measuring device 26 may further comprise a dispenser 35 for reagents. The dispenser 35 preferably comprises an actuation element 36 and interchangeable depot 33, which is designed, for example, as a blister and has a plurality of sealed containers in which reagents are arranged. After actuation of an actuating element 36, the seal 44 of the reagent chamber is broken in the case of a blister as depot 33, and the reagent is transferred via the feed device 34 into the dispensing section 22 and thus transferred into the microfluidic device 10.
    In order to ensure a sequence of the sample delivery, for example, a plurality of actuation elements 36 may be present, which have a sequence identifier, for example in the form of a numbering or by a color coding, for example as a type of traffic light system. This ensures that the sample is dispensed with closed cap and thus light-sealed sample carrier and that further the reagents or the sample to be analyzed can be delivered in the correct order, in the specified amount and especially when the cap is closed. Also, the depot can specify an activation direction, for example. In which the depot is rotatably received in the dispensing device and manually or automatically rotated after each reagent dispensing. An automatic indexing can be formed by a mechanical locking or snap device, which engages in a correspondingly shaped counter parts of the depot. A further development can also consist in that the control module has a Wirkverbin-fertil with the Betätigungsseiementen, and thus automatically and in the correct order dispenses the reagents. For this purpose, for example, a locking element 38 may further be formed with a contact device, whereby the closing of the cap 28 triggers the measuring process. For example, after the measurement has finished, N2010 / 24400 14/12 2010 DI 15:20 [SE / EM NR 7775] @ 025 15:29:10 14-12-2010 26/44 15:29:10 14-12-2010 26 The control module 37 controls the locking element 38 so that a mechanical latching device is deactivated and the cover cap 28 automatically engages in the latching element 38 Feeding and removal position 30 pivoted.
    In an advantageous development, the delivery device 34 may also be part of the depot 33, so that in the sense of a one-way use, the delivery device 34 is exchanged with the depot 33 and the reagents held therein after each use, so always a fresh, clean delivery device 34 for the measurement is used.
    However, the control module 37 is designed, in particular, to evaluate the individual photodetectors of the photosensitive sensor 5, in particular to evaluate the electrical signal proportional to the incident brightness signal, to condition it appropriately and to provide it to a communication connection 39. This communication port is preferably formed by a USB communication port, but further, wired or wireless communication connection from the field of data transmission are possible. Not conclusive examples are: RS-232, RS-435, Bluetooth, zigBEE, IRDA or Firewire.
    In addition to eherniiumineszenten measurements in which there is a light output due to the chemical bonding reaction in the test section, the measuring device 26 according to the invention can also perform transmissions measurements in which there is a change in the transmittance in the test section due to the chemical reaction. For this purpose, the cap 28 has a lighting device 40, which is preferably controlled by the control module 37 and emits a light having a specific wavelength or with a selectable or tunable wavelength in the direction of the sample carrier 2. The light penetrates the test sections and is attenuated to different extents according to the chemical reaction, which can be evaluated as a time course of the detected brightness signal.
    In addition, the illumination device 40 can additionally serve to calibrate the photosensitive sensor 5, in which the photosensitive sensor is illuminated before the measurement is carried out and the detected initial sacred value is stored as the calibration or zero point value. Thus, manufacturing-related irregularities or contamination of the individual photodetectors of the photosensitive sensor can be compensated, which is particularly advantageous when detecting reactions on several test sections, if the individual reactions are very different, so N2010 / 24400 14/12 2010 DI 15:20 [SE / EM NR 7775] Bl 0 26 15:29:28 14-12-2010 27/44
    If necessary, deviations would make up a relevant part of the measurement result and thus the measurement result would be significantly falsified.
    Furthermore, an identification feature 41 can be arranged on the sample carrier, which, for example, can be arranged as a unique serial number or type information in the form of a 1-resp. Applied 2-D codes Is. The identification feature 41 can also have a data memory, for example in the form of a data matrix code, for example by storing calibration data of the individual test sections or analyzer-relevant characteristic values. The identification feature 41 is read out by a read-out device 42 of the measuring device 26, wherein the read-out device 42 preferably communicates with the control module 37, which takes over the calibration or identification data, parameterizes the measuring device accordingly and performs the measurement.
    To ensure a repeat accuracy or to compensate for production-related deviations, it is advantageous that before dispensing the sample on the sample carrier, the lighting device is activated and a calibration of the photosensitive sensor is performed. By activating the illumination device, all photodetectors of the sensor are subjected to a uniform brightness signal or with a known brightness distribution, so that deviations from the desired brightness distribution can be interpreted as an interference signal and the detected halo signal corrected accordingly. In particular, slight variations in the reactivity of the applied sample chemistry may occur during the production of the test sections, or the individual photodetectors of the sensor may have slight sensitivity underscores. The arrangement of the sample carrier in the receiving section can also lead to slight misalignment or soiling, which results in a systematic error which, without correction or calibration, can significantly falsify the determined concentration values. This calibration can be performed only for the photodetectors alone, so with closed cap without inserted sample carrier, but it is also a calibration of the entire system possible, so if the sample carrier is inserted, but no sample or reagent was applied.
    The exemplary embodiments show possible embodiments of the measuring arrangement and the measuring device, wherein it should be noted at this point that the invention is not limited to the specifically illustrated embodiments of the same, but rather also various combinations of the individual embodiments with each other N2010 / 24400 14/12 2010 Dl 15: 20 [SE / EM NR 77751®027 15:29:47 14-12-2010 28/44 -24-possible, and this possibility of variation is due to the teaching of technical action by objective invention in the skill of those skilled in this technical field. So are all conceivable embodiments, which are possible by combinations of individual details of the illustrated and described embodiment variant, includes the scope of protection.
    FIGS. 6b and 6c show a further embodiment of the measuring device, which may be independent of itself, wherein the same reference numerals or component designations are used again for the same parts as in the preceding figures. In order to avoid unnecessary repetition, reference is made to the detailed description in the preceding pages.
    For the sake of order, it should finally be pointed out that for a better understanding of the structure of the measuring arrangement or of the measuring device, these or their components have been shown partially unequal-sized and / or enlarged and / or reduced in size.
    The task underlying the independent inventive solutions can be taken from the description.
    Above all, the individual embodiments shown in FIGS. 1 to 7 can form the subject of independent solutions according to the invention. The relevant tasks and solutions according to the invention can be found in the detailed descriptions of these figures. N2010 / 24400 14/12 2010 DT 15:20 [SE / EM NR 7775] ®028 IS; BO: 59 14-12-2010 34/44
    Reference numeral 41 Identifier 42 Read-out device 43 Boundary surface 44 Sealing
    Measuring arrangement Sample carrier Carrier layer Sample position Photosensitive sensor
    photodetector
    topcoat
    analysis layer
    test section
    Mikrofluldik
    distance
    thickness
    thickness
    Llchtaustrittsseite
    distance
    curve
    curve
    Number of sample intervals
    Aufnahmevorrichfung
    body
    dispensing portion
    channel
    Reservoir length
    gauge
    body
    cap
    swivel axis
    Feeding and removal position longitudinal direction
    Dichteiement
    depot
    Feeding device Dispensing device for reagents
    actuators
    control module
    locking element
    Communication Interface
    Illumination device N2010 / 24400 14/12 2010 DI 15:20 [SE / EM NR 7775] © 034
    权利要求:
    Claims (33)
    [1]
    25 15:29:58 14-12-2010 29/44 - 1 - Claims 1. Measuring arrangement (1) for the quantitative optical evaluation of a chemical reaction, comprising a sample carrier (2) with a carrier layer (3) and a sample layer (4) a photosensitive sensor (5) having a plurality of photodetectors (6) on a support body and with a transparent cover layer (7) arranged above the photodetectors (6), the support layer (3) having a delivery section (22) which extends over a Mlkrofluldik (10) with a reservoir (24) is connected, wherein the sample layer (4) has an analysis side (8) and this opposite a light exit side (14), wherein on the analysis side (8) in a longitudinal direction of the sample layer (2) spaced from each other, a plurality of test sections (9) are arranged and wherein the sample layer (4) with the analysis side (8) on the carrier layer (3) is arranged such that the test sections (9) facing a volume of the microfluidic (10)and wherein the sample carrier (2) is detachably arranged in a receiving device (20) so that the light exit side (14) faces the photosensitive sensor (5) and the test sections (9) are arranged above the photodetectors (6), characterized in that the distance (11) between the test sections (9) and the photodetectors (6) is less than 700pm.
    [2]
    2. Measuring arrangement according to claim 1, characterized in that the thickness (12) of the cover layer (7) is less than 500 pm.
    [3]
    3. Measuring arrangement according to one of claims 1 or 2, characterized in that the thickness (13) of the sample layer (4) is less than 200 pm.
    [4]
    4. Measuring arrangement according to one of claims 1 to 3, characterized in that the photosensitive sensor (5) has at least 32 photodetectors (6).
    [5]
    5. Measuring arrangement according to one of claims 1 to 4, characterized in that the gap between two adjacent photodetectors (6) is smaller than 150 pm. N2010 / 24400 14/12 2010 Tue 15:20 [SE / EM NR 7775] @) 029 15:30:11 14-12-2010 30/44 * * · -2-
    [6]
    6. Measuring arrangement according to one of claims 1 to 5, characterized in that at least 99.5% of a test section (9) outgoing and on the photosensitive sensor (5) incident electromagnetic radiation incident on a maximum of three photodetectors (6),
    [7]
    7. Measuring arrangement according to one of claims 1 to 6, characterized in that the photosensitive sensor (5) has at least two juxtaposed spaced rows of photodetectors (6),
    [8]
    8. Measuring arrangement according to one of claims 1 to 7, characterized in that the above the photodetector (5) arranged channel (23) of the Mlkrofluidik (10) has a length of 30 - 50mm, a width of 1 - 4mm and a height of 10 -200pm.
    [9]
    9. Measuring arrangement according to one of claims 1 to 8, characterized in that upon delivery of a sample at the Abgabeabschnftt (22) in the channel (23) forms a pressure gradient with a resulting capillary force in the direction of the reservoir (24).
    [10]
    10. Measuring arrangement according to one of claims 1 to 9, characterized in that the cover layer (7) of the photodetector (5) in the spectral range of 400 -600nm has a transparency maximum.
    [11]
    11. Measuring arrangement according to one of claims 1 to 10, characterized in that the center distance between two adjacent test sections (9) is greater than or equal to 3 times the center distance of the photodetectors (6).
    [12]
    12. Measuring arrangement according to one of claims 1 to 11, characterized in that the photosensitive sensor (5) arranged opposite boundary surface (43) of the channel (23), is optically reflective and / or that the carrier layer (3) optically reflective is finished.
    [13]
    13. Measuring arrangement according to one of claims 1 to 12, characterized in that the channel (23) for a photosensitive sensor (5) aligned concave N2010 / 24400 14/12 2010 DI 15:20 [SE / EM NR 77751 ®030 -3 - 15: 30.25 14-12-2010 31/44 -3- 15: 30.25 14-12-2010 31/44 • * • * * * • «4 · * t · * * • t 4 * · * • * · Has a cross-section or the channel (23) is concave in sections along its length.
    [14]
    14. Measuring arrangement according to one of claims 1 to 13, characterized in that the light exit side (14) at least partially has a light-guiding structure.
    [15]
    15. Measuring arrangement according to one of claims 1 to 14, characterized in that the Probeniage (4) and / or the cover layer (7) is formed as an optical fiber board, as a dense packing juxtaposed optical fibers.
    [16]
    16. Measuring arrangement according to one of claims 1 to 15, characterized in that the sample layer (4) in the direction of its thickness at least partially has a refractive index step profile.
    [17]
    17. Measuring arrangement according to one of claims 1 to 16, characterized in that the Probeniage (4) in the direction of their thickness at least in sections, a Bre-chungsindex Gradientenprofii.
    [18]
    18. Measuring arrangement according to one of claims 1 to 17, characterized in that on the light exit side (14) or on the cover layer (7) an immersion layer is applied.
    [19]
    19. Measuring arrangement according to one of claims 1 to 18, characterized in that on the sample carrier (2) an identity or Identmerkmerkmai (41) is arranged.
    [20]
    20. Measuring arrangement according to one of claims 1 to 19, characterized in that the sample layer (4) and / or the carrier layer (3) is designed as an optical polarizer.
    [21]
    21. Measuring device (28) for the optical evaluation of a chemical reaction comprising a measuring arrangement (1) with a photosensitive sensor (5) and a sample N2010 / 24400 14/12 2010 Dl 15:20 [SE / EM NR 7775] @ 031 15 : 30: 36 14-12-2010 32/44 25 -4-carrier (2), a base body (27), a pivotable about a pivot axis (29) between a measuring position and a feed and removal position (30) cap ( 28), furthermore a control module (37) for processing the brightness information detected by the sensor (5), wherein the sensor (5) is arranged in the base body (27) and wherein the cover cap (28) in the measuring position the sample carrier (2) and a Section of the base body (27) terminates light-tight against the environment, characterized in that the measuring arrangement (1) is designed according to one of claims 1 to 20.
    [22]
    22. Measuring device according to claim 21, characterized in that in the cover cap (28), a lighting device (40) is present.
    [23]
    23. A meter according to claim 21 or 22, characterized in that the illumination device (49) selectively controllable, emits light in several wavelengths and / or at different positions.
    [24]
    24. Measuring device according to one of claims 21 to 23, characterized in that the illumination device (49) has a polarizer.
    [25]
    25. Measuring device according to one of claims 21 to 24, characterized in that in the cap (28) or in the base body (27) is arranged a dispenser (35) for reagents.
    [26]
    26. Measuring device according to one of claims 21 to 25, characterized in that the dispensing device (35) has an actuating element (36) and a depot (33) for reagents.
    [27]
    27. A meter according to claim 26, characterized in that the depot is formed by a biister, wherein in each closed chambers reagents are present.
    [28]
    28. A meter according to any one of claims 26 or 27, characterized in that each depot is associated with an actuating element (36), wherein the actuating elements (36) are provided with a flow identifier. N2010 / 24400 14/12 2010 Tue 15:20 [SR / ΕΜ NR 7775] @ 032 15:30:50 14-12-2010 33/44 • Λ • · · -5
    [29]
    29. Measuring device according to one of claims 2 to 28, characterized in that the control module {37) with the actuating element (36), in particular a controllable contact means, is operatively connected.
    [30]
    30. Measuring device according to one of claims 26 to 29, characterized in that the depot (33) under the actuating element (36) is arranged pivotably.
    [31]
    31. A meter according to any one of claims 21 to 30, characterized in that the cover cap (28) has a feed section (34) which contacts the discharge section (22) of the Probentröger (2).
    [32]
    32. Measuring device according to one of claims 21 to 31, characterized in that for reading the identity feature (41), a non-contact readout device (42) is present.
    [33]
    33. Measuring device according to one of claims 21 to 32, characterized in that in the cover cap (28) a pressure means for exerting a force on the sample carrier (2) is arranged. Greiner Bio - One GmbH by Attorneys ^ uraerÄPartner Rechtsanwalt GmbH N2010 / 24400 14/12 2010 DI 15:20 ISE / EM NR 77751 @ 033
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    法律状态:
    2018-03-15| PC| Change of the owner|Owner name: GREINER BIO-ONE GMBH, AT Effective date: 20180201 |
    优先权:
    申请号 | 申请日 | 专利标题
    ATA2066/2010A|AT510750B1|2010-12-14|2010-12-14|Measurement arrangement for the quantitative optical evaluation of a chemical reaction|ATA2066/2010A| AT510750B1|2010-12-14|2010-12-14|Measurement arrangement for the quantitative optical evaluation of a chemical reaction|
    EP11799157.0A| EP2652479B1|2010-12-14|2011-12-14|Measuring arrangement for quantitative optical evaluation of a chemical reaction|
    PL11799157T| PL2652479T3|2010-12-14|2011-12-14|Measuring arrangement for quantitative optical evaluation of a chemical reaction|
    DK11799157.0T| DK2652479T3|2010-12-14|2011-12-14|Measurement equipment for quantitative optical evaluation of a chemical reaction|
    CN201180060060.7A| CN103430011B|2010-12-14|2011-12-14|For the measurement mechanism that the quantitative optical of chemical reaction is evaluated|
    US13/993,799| US9557260B2|2010-12-14|2011-12-14|Measuring arrangement for optically evaluating a chemical reaction quantitatively|
    PCT/EP2011/072763| WO2012080339A1|2010-12-14|2011-12-14|Measuring arrangement for optically evaluating a chemical reaction quantitatively|
    BR112013014930-2A| BR112013014930B1|2010-12-14|2011-12-14|measuring circuit for the optical quantitative evaluation of a chemical reaction|
    ES11799157.0T| ES2526075T3|2010-12-14|2011-12-14|Measurement arrangement for quantitative optical evaluation of a chemical reaction|
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