PREPARATION DEVICE, DIAGNOSTIC APPARATUS, DIAGNOSTIC KIT AND DIAGNOSTIC SYSTEM

Abstract

A preparation device (1) for preparing a sample for measurement of a target biomolecule in a sample of a bodily fluid, such as anti-Mullerian hormone in blood, comprises a substrate (12) with a capillary network configured to transport the sample of the bodily fluid along the substrate, wherein the substrate (12) is provided with a fluorescent, reflective or self-luminescent marker adapted to bind with the target biomolecule, said fluorescent, reflective or self-luminescent marker being adapted, when bound to the target biomolecule and excited by an excitation source of a diagnostic apparatus, together with the target biomolecule to emit reaction radiation at an intensity proportional to a quantity of the target biomolecule in the probe of the bodily fluid. The preparation device may preferably comprise a near-field communication (NFC) chip (114) storing a unique identifier of the preparation device.

Claims

1.-36. (canceled)

37. A preparation device for preparing a sample for measurement of a target biomolecule in a probe of a bodily fluid, the preparation device comprising: a substrate with a capillary network configured to transport the probe of the bodily fluid along the substrate, wherein the substrate is provided with a fluorescent, reflective or self-luminescent marker adapted to bind with the target biomolecule to emit a reaction radiation, eventually, when excited by an excitation source, and wherein the fluorescent, reflective or self-luminescent marker is adapted, when bound to the target biomolecule and, eventually, excited by the excitation source, together with the target biomolecule to emit the reaction radiation at an intensity proportional to a quantity of the target biomolecule in the probe of the bodily fluid.

38. The preparation device of claim 37, further comprising a case housing the substrate, wherein the case is adapted to cooperate with a diagnostic apparatus comprising the excitation source, for the measurement of a quantity of the target biomolecule in the probe of the bodily fluid, based on the intensity of the emitted reaction radiation, and wherein the case preferably has a window for indicating when predefined quantity of the probe of the bodily fluid is collected.

39. The preparation device of claim 37, wherein the target biomolecule is an anti-mullerian hormone indicative of an ovarian reserve of an individual to whom the bodily fluid sample belongs, and the fluorescent, reflective or self-luminescent marker comprises an anti-mullerian hormone antibody in a known concentration.

40. The preparation device of claim 37, wherein the fluorescent, reflective or self-luminescent marker comprises a protein displaying an intrinsic fluorescence.

41. The preparation device of claim 37, further comprising a calibration marker to validate the correct functioning of the preparation device by checking on a relationship between values measured of the preparation device and corresponding known values derived from a standard function, wherein the calibration marker preferably comprises a protein, such as a -fetoprotein or Vitamin D, and wherein the calibration marker preferably is arranged in a line on the reaction area.

42. The preparation device of claim 37, wherein the fluorescent, reflective or self-luminescent marker is arranged such that, when bound to the target biomolecule and excited by the excitation source, the intensity of the emitted reaction radiation is measurable in a spectral emission curve, and wherein the power spectrum of the radiation emission comprises a peak corresponding to the quantity of the target biomolecule in the probe of the bodily fluid.

43. The preparation device of claim 37, further comprising a wireless communication arrangement storing a unique identifier of the preparation device.

44. The preparation device of claim 43, wherein the wireless communication arrangement is integral with the case.

45. The preparation device of claim 43, wherein the wireless communication arrangement is writable and is adapted to keep record of usage of the preparation device.

46. The preparation device of claim 45, wherein the wireless communication arrangement is adapted to store a quantity value of the target biomolecule in the probe of the bodily fluid measured by a diagnostic apparatus and/or a unique identifier of the diagnostic apparatus.

47. The preparation device of claim 43, wherein the wireless communication arrangement is adapted to store calibration information, information for identification of the biological ingredients used in the preparation device and information for traceability of the biological ingredients used in the preparation device.

48. A diagnostic apparatus for the measurement of a quantity of target biomolecule in a probe of a bodily fluid prepared by the preparation device according to claim 37, comprising: a seat arranged to accommodate the preparation device in a predefined position and orientation; an excitation source adapted to illuminate a substrate of the preparation device; an optical assembly adapted to measure power spectral intensity values of a reaction radiation emitted by a product of reaction on the preparation device, wherein the power spectral intensity values are proportional to a quantity of the target biomolecule in the probe of the bodily fluid; and an electronic assembly adapted to process and convert the power spectral intensity values measured by the optical assembly to a quantity value of the target biomolecule in the probe of the bodily fluid, wherein the electronic assembly comprises a data exchange equipment adapted to receive data from the preparation device and to send data to a remote handheld communication device adapted to receive and display the quantity value of the target biomolecule in the probe of the bodily fluid.

49. The diagnostic apparatus of claim 48, further comprising a database storage adapted to store quantity values of the target biomolecule in the probe of the bodily fluid.

50. The diagnostic apparatus of claim 48, wherein the data exchange equipment comprises a near field communication structure adapted to store a unique identifier of the diagnostic apparatus and adapted to exchange data with a near field communication arrangement of the preparation device.

51. The diagnostic apparatus of claim 48, further comprising a housing having the seat and, preferably a guide for sliding the preparation device relative to the housing into the predefined position and orientation.

52. The diagnostic apparatus of claim 51, wherein, when the preparation device is arranged in the seat of the housing, the optical assembly is arranged to ensure a first measurement alignment between the excitation source and the substrate of the preparation device illuminated by the excitation source and to ensure a second measurement alignment between the substrate of the preparation device emitting the reaction light and the electronic assembly.

53. The diagnostic apparatus of claim 48, wherein the optical assembly is arranged to subtract illumination light by the excitation source from a light reflected by the preparation device such that the reaction light emitted by the product of reaction on the substrate of the preparation device is isolated.

54. The diagnostic apparatus of claim 53, wherein the electronic assembly comprises a photo sensor adapted to measure the reaction light emitted by the product of reaction on the substrate of the preparation device, once isolated from the illumination light by the excitation source.

55. The diagnostic apparatus of claim 54, wherein the electronic assembly comprises a digital processor programmed to execute algorithms on a signal corresponding to the measured quantity value of the target biomolecule in the probe of the bodily fluid, and/or comprising an analog-to-digital converter cooperating with the photo sensor for digitalization of the measured quantity value of the target biomolecule in the probe of the bodily fluid.

56. The diagnostic apparatus of claim 48, wherein the electronic assembly comprises an energy storage device, such as a battery or accumulator and/or a connection to an external power supply, adapted to power electronic components of the diagnostic apparatus.

57. The diagnostic apparatus of claim 48, wherein the data exchange equipment of the electronic assembly is configured to identify the remote handheld communication device of an authorized user and to send data exclusively to the authorized remote handheld communication device, and wherein the data exchange equipment of the electronic assembly preferably is configured to identify the remote handheld communication device by providing a unique pairing identification to the remote handheld communication device and by receiving a match signal from the remote handheld communication device.

58. The diagnostic apparatus of claim 48, further comprising an imager arranged to generate image data of the quantity value of the target biomolecule in the probe of the bodily fluid, wherein the data exchange equipment of the electronic assembly is configured to send the image data to the remote handheld communication device.

59. A diagnostic system comprising: a preparation device having a substrate with a capillary network configured to transport the probe of the bodily fluid along the substrate, wherein the substrate is provided with a fluorescent, reflective or self-luminescent marker adapted to bind with the target biomolecule to emit a reaction radiation, eventually, when excited by an excitation source, and wherein the fluorescent, reflective or self-luminescent marker is adapted, when bound to the target biomolecule and, eventually, excited by the excitation source, together with the target biomolecule to emit the reaction radiation at an intensity proportional to a quantity of the target biomolecule in the probe of the bodily fluid; a diagnostic apparatus having a seat arranged to accommodate the preparation device in a predefined position and orientation, an excitation source adapted to illuminate a substrate of the preparation device, an optical assembly adapted to measure power spectral intensity values of a reaction radiation emitted by a product of reaction on the preparation device, wherein the power spectral intensity values are proportional to a quantity of the target biomolecule in the probe of the bodily fluid, and an electronic assembly adapted to process and convert the power spectral intensity values measured by the optical assembly to a quantity value of the target biomolecule in the probe of the bodily fluid, wherein the electronic assembly comprises a data exchange equipment adapted to receive data from the preparation device and to send data to a remote handheld communication device adapted to receive and display the quantity value of the target biomolecule in the probe of the bodily fluid; a server; and a mobile communication device adapted to communicate with the diagnostic apparatus and the server, wherein the server is arranged to receive data signals from the mobile communication device corresponding to measured quantity values of a target biomolecule in probes of a bodily fluid and to send data signals to the mobile communication device corresponding to an evaluation of the measured quantity values.

60. The diagnostic system of claim 59, wherein the server comprises a data storage and is adapted to anonymize data received from the mobile communication device, to store the anonymized data in the data storage, to evaluate the stored data with respect to a specific topic and to provide results of the evaluation of the stored data, wherein providing the results of the evaluation of the stored data preferably comprises sending data signals corresponding to the results of the evaluation of the stored data to the mobile communication device, and/or evaluating the stored data with respect to a specific topic preferably comprises generating a forecast of a medical outcome for a specific user.

61. The diagnostic system of claim 60, wherein the diagnostic system is arranged to be applied for pharmacovigilance or clinical trials.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0051] The preparation device according to the invention, the diagnostic apparatus according to the invention, the diagnostic system according to the invention and the diagnostic kit according to the invention are described in more detail herein below by way of an exemplary embodiment and with reference to the attached drawings, in which:

[0052] FIG. 1 shows a schematic perspective view of an embodiment of the preparation device according to the invention;

[0053] FIG. 2 shows a schematic perspective view of some interior components of the preparation device of FIG. 1;

[0054] FIG. 3 shows schematic view of an embodiment of a diagnostic system comprising an embodiment of an diagnostic apparatus according to the invention having the preparation device of FIG. 1;

[0055] FIG. 4 shows a schematic view of an embodiment of a diagnostic kit according to the invention having the preparation device of FIG. 1; and

[0056] FIG. 5 shows a graph of a measured spectrum of light reflection provided within the diagnostic system of FIG. 3.

DESCRIPTION OF EMBODIMENTS

[0057] In the following description, certain terms are used for reasons of convenience and are not intended to limit the invention. The terms right, left, up, down, under and above refer to directions in the figures. The terminology comprises the explicitly mentioned terms as well as their derivations and terms with a similar meaning. Also, spatially relative terms, such as beneath, below, lower, above, upper, proximal, distal, and the like, may be used to describe one element's or feature's relationship to another element or feature as illustrated in the figures. These spatially relative terms are intended to encompass different positions and orientations of the devices in use or operation in addition to the position and orientation shown in the figures. For example, if a device in the figures is turned over, elements described as below or beneath other elements or features would then be above or over the other elements or features. Thus, the exemplary term below can encompass both positions and orientations of above and below. The devices may be otherwise oriented (rotated 90 degrees or at other orientations), and the spatially relative descriptors used herein interpreted accordingly. Likewise, descriptions of movement along and around various axes include various special device positions and orientations.

[0058] To avoid repetition in the figures and the descriptions of the various aspects and illustrative embodiments, it should be understood that many features are common to many aspects and embodiments. Omission of an aspect from a description or figure does not imply that the aspect is missing from embodiments that incorporate that aspect. Instead, the aspect may have been omitted for clarity and to avoid prolix description. In this context, the following applies to the rest of this description: If, in order to clarify the drawings, a figure contains reference signs which are not explained in the directly associated part of the description, then it is referred to previous or following description sections. Further, for reason of lucidity, if in a drawing not all features of a part are provided with reference signs it is referred to other drawings showing the same part. Like numbers in two or more figures represent the same or similar elements.

[0059] FIG. 1 shows an embodiment of a preparation device 1 according to the invention. The preparation device 1 comprises an elongated cuboid case 11 made of a disposable rigid plastic material. From left to right a top side of the case 11 is provided with a round sample collecting opening 112, an elongated transverse window 111 and a main see-through portion 113. Through the see-through portion 113 an interior of the case 11 is visible in which a substrate 12 is arranged.

[0060] In a side wall of the case 11 a near field communication (NFC) chip 114 is embedded such that it is integral with the case 11. In the NFC chip 114 a unique ID of the preparation device 1 is stored such that it is automatically traceable and derivable which specific preparation device 1 is processed. The NFC chip 114 is writable and is adapted to keep record of usage of the preparation device 1. In particular, a quantity value derived by means of the preparation device 1 and calibration data can be stored in the NFC chip 114.

[0061] In FIG. 2 a test strip arranged in the interior of the casing 11 is shown in more detail. Thereby, it can be seen that the test strip comprises the strip shaped substrate which is partially covered by a stabilizing structure 16. In particular, the stabilizing structure comprises a back card 161 forming the bottom of the test strip on which the substrate 12 is placed. Besides both longitudinal ends of the substrate 12 a side card 163 is arranged on the back card 161 and on top of the side cards 163 and the substrate a top card 162 is arranged. The top card 162 only partially covers the top side of the substrate 12. In particular, a section of the top side of the substrate 12 corresponding to the see-through portion 113 of the case 11 is open.

[0062] On the left-hand side a sample pad 15 is positioned on the top card 162. The sample pad 15 is located beneath the sample collecting opening 112 when the test strip is inside the case 11 such that a bodily fluid, i.e. blood, provided through the sample collecting opening 112 is received and gathered by the sample pad 15 as a reservoir. The sample pad 15 is in fluid connection with the substrate 12.

[0063] The substrate 12 is equipped with a capillary network configured to transport the blood. In particular, when a probe of blood of a patient is provided through the sample collecting opening 112 into the sample pad 15, a portion of it is forwarded to the substrate 12 and transported along the substrate 12 by and via its capillary network. The substrate 12 is provided with a predefined concentration of a fluorescent marker having an antibody capable of binding to anti-mullerian hormone (AMH) as target biomolecule. Thereby, the fluorescent marker emits a reaction light as reaction radiation when excited by a light source as excitation source. In particular, when bound to AMH and excited by the light source, the fluorescent marker emits the reaction light at an intensity proportional to a quantity of AMH in the probe of blood. In particular, the substrate 12 is embodied such that the fluorescent marker bound to AMH is visible at a concentration line 13 on the top surface of the substrate 12.

[0064] The substrate 12 is further provided with a fluorescent calibration marker comprising -fetoprotein or Vitamin D. It is capable to validate the correct functioning of the preparation device 1 by checking on a relationship between measured values and corresponding known values derived from a standard function. In particular, the substrate 12 is embodied such that the calibration marker bound to AMH is visible at a calibration line 14 on the top surface of the substrate 12.

[0065] FIG. 3 shows an embodiment of a diagnostic system 5 comprising an embodiment of a diagnostic apparatus 2, the preparation device 1, a smartphone 3 as mobile communication device and a server 4. The diagnostic apparatus 2 has a housing 21 equipped with seat 211. The seat 211 is embodied as a laterally open slit dimensioned to guide the preparation device 1 from left to right into a predefined position and alignment inside the diagnostic apparatus 2.

[0066] The diagnostic apparatus 2 has two light sources 22 as radiation sources or excitation sources and an optical assembly with two photo sensors 23. The left one of the light sources 22 together with the left one of the photo sensors 23 are arranged adjacent to the concentration line 13 of the substrate 12. Thereby, the left-hand photo sensor 23 is arranged to receive light of the left-hand light source 22 reflected by the fluorescent marker bound to AMH at the concentration line 13. In particular, the optical assembly is adapted to measure power spectral intensity values of the reaction light emitted by a product of reaction on the preparation device 1, wherein the power spectral intensity values are proportional to a quantity of the AMH in the probe of blood.

[0067] Similarly, the right one of the light sources 22 together with the right one of the photo sensors 23 are arranged adjacent to the calibration line 14 of the substrate 12. Thereby, the right-hand photo sensor 23 is arranged to receive light of the right-hand light source 22 reflected by the calibration marker bound to AMH at the calibration line 13.

[0068] The diagnostic apparatus 2 further comprises a power supply 27 and an electronic assembly with a processor 25. The power supply 27 is arranged to deliver electric energy to all electronic components of the diagnostic apparatus 2. The processor 25 is arranged to process and convert the power spectral intensity values measured by the optical assembly to a quantity value of the AMH in the probe of blood. The electronic assembly further has a data Wireless Local Area Network (WLAN) adapter 24 and a NFC chip 26 as exchange equipment. The NFC chip 26 is adapted to receive data from the preparation device 1 via its NFC chip 114. The WLAN adapter 24 is embodied to send data to the smartphone 3. The smartphone 3 runs a dedicated software adapting the smartphone 3 to receive and display the quantity value of AMH in the probe of blood.

[0069] The smartphone 3 is further connected to the server 4, e.g., via the Internet. The server 4 is arranged to receive data signals from the smartphone 3 which data signals correspond to measured quantity values of the AMH in the probe of blood. It is further adapted to send data signals to the smartphone corresponding to an evaluation of the measured quantity value.

[0070] More specifically, the server 4 comprises a data storage and is adapted to anonymize data received from the smartphone, to store the anonymized data in the data storage, to evaluate the stored data with respect to a specific topic and to provide results of the evaluation of the stored data. The smartphone 3 receives data signals corresponding to the results of the evaluation of the stored data from the server 5. Such results can, e.g., be related to a forecast of a medical outcome for the patient.

[0071] In FIG. 4 a kit 6 is shown comprising a box 65 in which one preparation device 1, two lancets 63, a disinfection wipe 61, a plaster 62 and a instructions manual 64 are arranged. Thereby, the kit 6 provides a patient with everything required for a test cycle.

[0072] FIG. 5 shows a graph of the function of the energy spectrum of the reflected light detected by the left hand photo sensor 22. In particular, the intensity of the reflected light is displayed versus the wavelength of the light. To derive the concentration from this graph it would mathematically be required to integrate the curve. However, since the function has a clear and sharp peak the concentration can be correlated to the height of the peak which makes a very efficient evaluation of the concentration possible at an appropriate accuracy.

[0073] This description and the accompanying drawings that illustrate aspects and embodiments of the present invention should not be taken as limiting-the claims defining the protected invention. In other words, while the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive. Various mechanical, compositional, structural, electrical, and operational changes may be made without departing from the spirit and scope of this description and the claims. In some instances, well-known circuits, structures and techniques have not been shown in detail in order not to obscure the invention. Thus, it will be understood that changes and modifications may be made by those of ordinary skill within the scope and spirit of the following claims. In particular, the present invention covers further embodiments with any combination of features from different embodiments described above and below.

[0074] The disclosure also covers all further features shown in the FIGS. individually although they may not have been described in the afore or following description. Also, single alternatives of the embodiments described in the figures and the description and single alternatives of features thereof can be disclaimed from the subject matter of the invention or from disclosed subject matter. The disclosure comprises subject matter consisting of the features defined in the claims or the exemplary embodiments as well as subject matter comprising said features.

[0075] Furthermore, in the claims the word comprising does not exclude other elements or steps, and the indefinite article a or an does not exclude a plurality. A single unit or step may fulfil the functions of several features recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. The terms essentially, about, approximately and the like in connection with an attribute or a value particularly also define exactly the attribute or exactly the value, respectively. The term about in the context of a given numerate value or range refers to a value or range that is, e.g., within 20%, within 10%, within 5%, or within 2% of the given value or range. Components described as coupled or connected may be electrically or mechanically directly coupled, or they may be indirectly coupled via one or more intermediate components. Any reference signs in the claims should not be construed as limiting the scope.