TRANSMISSION APPARATUS AND METHOD FOR EXAMINING AT LEAST ONE SAMPLE IN A MICROTITER PLATE BY MEANS OF TRANSMISSION

Abstract

A transmission device for examining at least one sample in a microtiter plate, the transmission device including: an illumination device; and a detection device, an intermediate space being formed between the illumination device and the detection device, the intermediate space being configured to receive a microtiter plate. The illumination device including at least one emission source, the illumination device being configured to guide emission light generated by the emission source through the intermediate space. The detection device including at least one detector configured to measure light signals received from the intermediate space; and the detection device includes an angle-dependent filter arranged between the illumination device and the at least one detector in a beam path of the emission light, the angle-dependent filter being configured to substantially only let through light beams having an angle of incidence smaller than a predetermined critical angle.

Claims

1. A transmission device for examining at least one sample in a microtiter plate, the transmission device comprising: an illumination device; and a detection device, an intermediate space being formed between the illumination device and the detection device, the intermediate space being configured to receive a microtiter plate: wherein the illumination device comprising at least one emission source, the illumination device being configured to guide emission light generated by the emission source through the intermediate space; the detection device comprising at least one detector configured to measure light signals received from the intermediate space; and the detection device comprises an angle-dependent filter arranged between the illumination device and the at least one detector in a beam path of the emission light, the angle-dependent filter being configured to substantially only let through light beams having an angle of incidence smaller than a predetermined critical angle.

2. The transmission device according to claim 1, wherein the angle-dependent filter is configured as a film.

3. The transmission device according to claim 1, wherein the angle-dependent filter is configured as a monitor filter having parallel lamellae.

4. The transmission device according to claim 1, wherein the intermediate space is formed as a rectangular opening in the transmission device such that the transmission device is configured as an open measuring assembly and the microtiter plate inserted in the intermediate space is accessed without the need for confirmation of a closure element.

5. The transmission device according to claim 1, wherein the intermediate space substantially matches a shape of the microtiter plate inserted in the intermediate space.

6. The transmission device according to claim 1, wherein the illumination device is configured to split the emission light generated by the emission source onto a plurality of partial beam paths, each of the plurality of partial beam paths extending as transmission beam paths through the intermediate space to a corresponding detector of the detection device, each detector comprising the at least one detector.

7. The transmission device according to claim 6, wherein at least one of the plurality of partial beam paths is a reference beam path provided for guiding the emission light to a reference detector arranged in the illumination device.

8. The transmission device according to claim 6, wherein the illumination device comprises a light mixer configured to homogenize the emission light generated by the emission source and to distribute the emission light with equal intensity onto the plurality of partial beam paths

9. The transmission device according to claim 8, wherein the light mixer having a rectangular cross-section.

10. The transmission device according to claim 8, wherein the plurality of partial beam paths in the illumination device each extend in an optical waveguide, an entry side of each optical waveguide adjoins the light mixer so as to be bundled together, the optical waveguides in which the transmission beam paths extend being configured to guide a portion of the emission light from the light mixer to a corresponding emission opening of the illumination device.

11. The transmission device according to claim 10, wherein the emission openings are formed as cut-outs in a holding plate.

12. The transmission device according to claim 10, further comprising a spherical lens arranged in each emission opening.

13. The transmission device according to claim 8, wherein the emission source comprises at least two light emitting diodes, emission light from the at least two light-emitting diodes being gathered in the light mixer, an interference filter being arranged between each of the at least two light-emitting diodes and the light mixer.

14. The transmission device according to claim 13, further comprising a first spherical lens arranged in front of each interference filter and a second spherical lens being arranged behind each interference filter.

15. The transmission device according to claim 13, wherein a wavelength of each of the at least two light-emitting diodes being selected from a group consisting of 405 nm, 450 nm, 540 nm and 630 nm.

16. A method for examining at least one sample in a microtiter plate by transmission of emission light generated during a first period of time in an illumination device from an emission source, the emission light being guided through at least one cavity of the microtiter plate in which the at least one sample is located, light signals received from the at least one cavity being measured by at least one detector arranged in a detection device during the first period of time, that the method comprising: protecting the at least one detector from incident scattered light by an angle-dependent filter arranged between the illumination device and the at least one detector in a beam path of the emission light; and substantially only letting through light beams of which an angle of incidence is smaller than a predetermined critical angle.

17. The method according to claim 16, further comprising: measuring the light signals during the first period of time where emission light is guided through the at least one cavity; measuring the light signals during a second period of time during a dark measurement where no emission light is guided through the at least one cavity; and subtracting the light signals measured during the second period of time from the light signals measured during the first period of time.

18. The method according to claim 17, further comprising repeating the measuring steps and the subtracting step for each of a plurality of cycles.

19. The method according to claim 16, further comprising splitting the emission light up; guiding the split emission light through a plurality of cavities of the microtiter plate at a same time, and measuring the light signals of each cavity by a corresponding detector comprising the at least one detector.

20. The method according to claim 16, further comprising: measuring one or more of an aging of the emission source and a change in an intensity of the emission light from the emission source using a reference measurement, the emission light being guided along a reference beam path to a reference detector arranged in the illumination device to detect the intensity of the emission light; and comparing the intensity of the emission light with one or more of previously measured values and predefined values for the intensity of the emission light.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0052] Further features will become apparent from the description of embodiments together with the claims and the attached drawings. Embodiments can fulfill individual features or a combination of several features.

[0053] The embodiments are described below, without restricting the general idea of the invention, using exemplary embodiments with reference to the drawings, express reference being made to the drawings with regard to all details that are not explained in greater detail in the text. In the following:

[0054] FIG. 1 illustrates a diagram of a transmission device for examining at least one sample in a microtiter plate,

[0055] FIG. 2 illustrates a diagram of a microtiter plate having ninety-six cavities,

[0056] FIG. 3 illustrates a diagram of an illumination device,

[0057] FIG. 4 illustrates a diagram showing the internal structure of an illumination device comprising an emission source,

[0058] FIG. 5 illustrates the diagram from FIG. 4 with optical waveguides also shown,

[0059] FIG. 6 illustrates a diagram of a detection device,

[0060] FIG. 7 illustrates an exploded diagram of a detection device,

[0061] FIG. 8 illustrates a diagram showing the functioning of a monitor filter.

[0062] In the drawings, the same or similar elements and/or parts are provided with the same reference numbers in order to prevent the item from needing to be reintroduced.

DETAILED DESCRIPTION

[0063] FIG. 1 schematically shows an exemplary embodiment of a transmission device 1. The transmission device 1 comprises an illumination device 2 and a detection device 4, between which there is an intermediate space 6 formed as a rectangular opening. The intermediate space 6 is configured such that a microtiter plate 8 of the like shown in FIG. 2 can be inserted so as to fit exactly therein. The dimensions of the intermediate space 6 therefore substantially correspond to the dimensions of the microtiter plate 8, as a result of which the transmission device 1 has a compact design. Furthermore, the transmission device 1 comprises a plurality of status lights 3. Said status lights 3 are in each case assigned to one light-emitting diode arranged in the illumination device 2. The light-emitting diodes are hidden in FIG. 1. When one of the light-emitting diodes emits light, the assigned status light 3 also lights up. For reasons of clarity, only one of the status lights 3 has been provided with a reference sign.

[0064] The microtiter plate 8 shown by way of example in FIG. 2 is of a format having ninety-six cavities 80, and once again only one of these cavities 80 has been provided with a reference sign. The samples to be examined are arranged in these cavities 80 before the microtiter plate 8 is inserted into the intermediate space 6. Since the dimensions of microtiter plates 8 meet an ANSI standard, the intermediate space 6 can be configured to be complementary in shape to these dimensions.

[0065] FIG. 3 is a diagram of the illumination device 2, whereby a view obliquely from below has been selected for FIG. 3. The illumination device 2 comprises an ejection device 29, by means of which the microtiter plate 8 can be quickly and simply ejected from the intermediate space 6. A holding plate 28 comprising a number of emission openings 27, of which only one has been provided with a reference sign, is arranged directly above the inserted microtiter plate 8. The number of emission openings 27 corresponds to the number of cavities 80 in the microtiter plate 8. Therefore, in the example shown in FIG. 3, there are ninety-six emission openings 27. The emission openings 27 are arranged such that, when the microtiter plate 8 is inserted, each emission opening 27 is arranged centrally over a cavity 80.

[0066] The internal structure of the illumination device 2 is shown in FIGS. 4 and 5. The view selected for FIGS. 4 and 5 corresponds to the view in FIG. 1, and therefore the bottom of the holding plate 28 hidden in FIGS. 4 and 5 corresponds to the bottom of the holding plate 28 shown in FIG. 3. The illumination device 2 comprises an emission source 20, which comprises four light-emitting diodes 21a, 21b, 21c, 21d in the example shown in FIG. 4. By way of example, the emission light of the light-emitting diode 21a has a wavelength of 405 nm, the emission light of the light-emitting diode 21b has a wavelength of 450 nm, the emission light of the light-emitting diode 21c has a wavelength of 540 nm and the emission light of the light-emitting diode 21d has a wavelength of 630 nm. By providing a plurality of light-emitting diodes with different wavelengths, various examinations can be performed using the same transmission device 1. A spherical lens 23 that parallelizes the exiting emission light is in each case arranged directly behind the light-emitting diodes 21a to 21d. For reasons of clarity, again only one of the spherical lenses 23 has been provided with a reference sign. An interference filter 22 that restricts the wavelength spectrum of the emission light from the light-emitting diodes 21a to 21d is arranged behind each spherical lens 23. According to another embodiment not shown in FIG. 4, an additional spherical lens that focuses the emission light is arranged behind each interference filter 22.

[0067] A light mixer 24 is arranged behind the interference filters 22 or the additional spherical lenses. Said light mixer 24 homogenizes the incident emission light such that it is distributed with equal intensity in the cross-section of the light mixer 24. For this purpose, according to the embodiment shown in FIG. 4, the light mixer 24 has a rectangular cross-section. If only one individual light-emitting diode 21a is provided, the light mixer 24 for example has the shape of a rod with a rectangular cross-section. However, if a plurality of light-emitting diodes 21a to 21d are provided, as shown in FIG. 4, the light mixer 24 gathers the emission light from the light-emitting diodes 21a to 21d. As shown in FIG. 4, this may for example be done by means of four converging arms. Alternatively, the light mixer 24 may have a substantially triangular base surface, which, when compared with the embodiment shown in FIG. 4, occupies the area between the arms.

[0068] FIG. 5 shows the diagram from FIG. 4 enlarged. Partial beam paths 25 are also schematically shown, onto which the emission light of the light-emitting diodes 21a to 21d exiting the optical waveguide 24 is split. For this purpose, a bundle of optical waveguides 26 into which an equal portion of the emission light is coupled in each case is arranged at the exit of the light mixer 24. Said optical waveguides 26 each lead from the exit of the light mixer 24 to an emission opening 27 in which a spherical lens (not shown) for focusing the emission light is arranged in each case. The partial beam paths 25 that extend in the optical waveguides 26 to the emission openings 27 are transmission beam paths. An additional optical waveguide 26, as a reference beam path 30, leads back to a reference detector unit 32, which is arranged next to the light-emitting diodes 21a to 21d. By means of this reference detector unit 32, aging of the light-emitting diodes 21a to 21d and/or a change in the intensity of the emission light can be determined.

[0069] FIG. 6 schematically shows a detection device 4 that is arranged below the illumination device 2 and the inserted microtiter plate 8. In a region of the surface of the detection device 4 that substantially corresponds to the surface area of the inserted microtiter plate 8, the detection device 4 comprises an angle-dependent filter 42 that is configured as a film in the diagram in FIG. 6. Said angle-dependent filter 42 is configured to substantially only let through light beams of which the angle of incidence is smaller than a predetermined critical angle. The critical angle is related to the transmission beam paths of the emission light in the intermediate space 6, which corresponds to a vertical line on the angle-dependent filter 42. In this way, scattered light, which is incident in the intermediate space 6 at an oblique angle, is prevented from passing through the angle-dependent filter 42, and therefore only the light signals from the samples in the intermediate space 6 can pass through.

[0070] FIG. 7 shows an exploded diagram of the detection device 4 from FIG. 6. FIG. 7 shows that a detector plate 49 is arranged below the angle-dependent filter 42, which detector plate comprises a series of detector openings 41 arranged centrally below the emission openings 27 and cavities 80 in each case. A detector unit having at least one detector 40 is arranged in each of these detector openings 41. Said detector units are hidden due to the perspective in FIG. 7. The detectors 40 are for example photodiodes that are sensitive to different wavelength ranges. Spherical lenses 43 are in each case arranged in the openings in order to focus the emission light or the light signals onto the detectors 40.

[0071] Taking FIGS. 3, 5 and 7 together, it is clear that each of the transmission beam paths extends from the light mixer 24 through an optical waveguide 26, an emission opening 27, the intermediate space 6 or a cavity 80, and the angle-dependent filter 42 to a detector 40 or detector unit. After exiting the emission openings 27, the transmission beam paths extend in parallel with one another.

[0072] The functioning of a monitor filter is shown schematically in FIG. 8. A monitor filter of this kind may for example be used as an angle-dependent filter 42. The monitor filter comprises a series of lamellae 44 arranged in parallel with one another. When light is incident along a vertical line 47 in the monitor filter, it can pass unhindered through the monitor filter on account of the small width of the lamellae 44. However, if the angle of incidence 46 of a light beam 45 in the transverse direction of the lamellae is greater than a critical angle 48, the light beam 45 cannot pass through the monitor filter.

[0073] In order to prevent the incidence of scattered light, the monitor filter can be arranged in the transmission device 1 such that the transverse direction of the lamellae 44 corresponds to the direction of the opening of the intermediate space 6.

[0074] While there has been shown and described what is considered to be preferred embodiments, it will, of course, be understood that various modifications and changes in form or detail could readily be made without departing from the spirit of the invention. It is therefore intended that the invention be not limited to the exact forms described and illustrated, but should be constructed to cover all modifications that may fall within the scope of the appended claims.

LIST OF REFERENCE SIGNS

[0075] 1 Transmission device

[0076] 2 Illumination device

[0077] 3 Status light

[0078] 4 Detection device

[0079] 6 Intermediate space

[0080] 8 Microtiter plate

[0081] 20 Emission source

[0082] 21a, 21b, 21c, 21d Light-emitting diode

[0083] 22 Interference filter

[0084] 23 Spherical lens

[0085] 24 Light mixer

[0086] 25 Partial beam paths

[0087] 26 Optical waveguide

[0088] 27 Emission opening

[0089] 28 Holding plate

[0090] 29 Ejection device

[0091] 30 Reference beam path

[0092] 32 Reference detector

[0093] 40 Detector

[0094] 41 Detector opening

[0095] 42 Angle-dependent filter

[0096] 43 Spherical lens

[0097] 44 Lamella

[0098] 45 Light beam

[0099] 46 Angle of incidence

[0100] 47 Vertical line

[0101] 48 Critical angle

[0102] 49 Detector plate

[0103] 80 Cavity