Filter device for an optical analysis device, and method for operating the optical analysis device

Abstract

The invention relates to a filter device comprising: a first filter carrier (10) having x first optical filters (11, 12); and a second filter carrier (20) having y second optical filters (21-23), wherein x and y each independently have a value of at least 2, and wherein the filter carriers (10, 20) are each designed such that one filter (11, 12, 21-23) of each filter carrier (10, 20) can be positioned in an optical path of the filter device. Each first optical filter (11, 12) transmits light in a first wavelength band (71, 72), and each second optical filter (21-23) transmits light in x second wavelength bands (81-86), wherein the first wavelength bands (71, 72) do not overlap, the second wavelength bands (81-86) do not overlap, and each first wavelength band (71, 72) contains a second wavelength band (81-86) from each of the second optical filters (21-23). An optical analysis device comprises a light source (41), a sample carrier (42), and an optical sensor (43). The filter device is arranged in an optical path between the light source (41) and the sample carrier (42) and / or in an optical path between the sample carrier (42) and the optical sensor (43). In a method for operating the optical analysis device, a sample (50) is arranged on the sample carrier (42), is excited to fluoresce by means of the light source (41), and light emitted by the sample (50) is detected by the optical sensor (43), wherein a fluorescence analysis of the sample is carried out in x · y optical channels.

Description

[0001] R. 415711

[0002] - 1 -

[0003] Description

[0004] title

[0005] Filter device for an optical analysis device and method for operating the optical analysis device

[0006] The present invention relates to a filter device. Furthermore, the present invention relates to an optical analysis device comprising the filter device. Finally, the present invention relates to a method for operating the optical analysis device.

[0007] State of the art

[0008] In devices for decentralized diagnostics, particularly PCR tests, multiplex assays can simultaneously detect a large number of different pathogens. These multiplex assays typically employ different fluorophores with specific excitation and emission spectra. To prevent cross-referencing of fluorophore emissions, such devices can only have a limited number of optical channels. An optical channel is defined as a combination of optical filters with a defined excitation and emission spectrum. The transmission spectrum of each excitation filter is typically assigned to only one transmission spectrum of an emission filter, with the transmission spectra being shifted relative to each other by the Stokes shift of the fluorophore being analyzed by the optical channel.Such optical channels are called diagonal or conventional channels. R. 415711.

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[0010] Disclosure of the invention

[0011] The filter device comprises a first filter carrier with x first optical filters and a second filter carrier with y second optical filters. x and y are natural numbers, each independently possessing a value of at least 2. The filter carrier is configured to position one filter from each filter carrier in a beam path of the filter device. Each first optical filter allows light of a specific first wavelength band to pass through. Each second optical filter allows light from x different second wavelength bands to pass through. The first wavelength bands do not overlap. The second wavelength bands also do not overlap. Each first wavelength band contains one second wavelength band of each of the second optical filters.

[0012] This filter device is particularly useful when the excitation wavelength band of one optical channel needs to be combined with the emission wavelength band of another optical channel. This creates so-called off-diagonal optical channels, which increase the total number of available optical channels in a multiplex measurement. Using such off-diagonal channels with conventional filter devices increases crosstalk between the channels. While this effect can be partially compensated for by calibration using an overflow matrix, it still increases the risk of misinterpreting an emission signal.Compared to a filter device with only one filter carrier with y optical filters, the present filter device increases both the number of diagonal optical channels and the number of non-diagonal optical channels available for multiplex analysis.

[0013] The optical filters are specifically designed as bandpass filters, whereby the first optical filters can be designed as longpass and shortpass filters, and the second optical filters can be designed as multibandpass filters. By selecting from the second wavelength bands of every second optical R. 415711

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[0015] By placing one of the first optical filters in the beam path, a specific second wavelength band can be selected while the other second wavelength bands are blocked. x • y wavelength bands can be unlocked using the filter device.

[0016] For a compact design of the filter device, it is advantageous that the filter holders are designed as filter slides.

[0017] In a preferred embodiment of the filter device, x = 2 and y = 3. The three second optical filters each allow the transmission of two different wavelength bands. By combining one of the second optical filters with one of the two first optical filters, one of the two wavelength bands of the second optical filter can be selected. In total, such a filter device thus provides six wavelength bands.

[0018] However, filter devices with more first and second optical filters are also possible. For example, if the values ​​x = 3 and y = 4 are chosen, 12 different wavelength bands are available.

[0019] The optical analysis device comprises a light source, a sample carrier, and an optical sensor. A filter device, as described above, is arranged in a beam path between the light source and the sample carrier and / or in a beam path between the sample carrier and the optical sensor. By arranging the filter device between the light source and the sample carrier, a specific wavelength range can be selected from the, for example, white light of the light source. By using the filter device between the sample carrier and the optical sensor, only fluorescence light of a predetermined wavelength band from a sample placed on the sample carrier and excited to fluorescence by the light source can reach the optical sensor. R. 415711

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[0021] To capture as much fluorescence light as possible, the beam path between the sample carrier and the optical sensor is preferably orthogonal to a plane formed by the sample carrier. The beam path between the light source and the sample carrier then forms an angle of less than 90° with the plane of the sample carrier. To implement this arrangement in the most space-saving way possible, it is preferred that a filter wheel be arranged in the beam path between the light source and the sample carrier, and that a filter device, as described above, be arranged in the beam path between the sample carrier and the optical sensor. The filter wheel can comprise a plurality of bandpass filters, each configured to allow light of a single wavelength band to pass through.

[0022] A space-saving design of the optical analysis device is particularly advantageous when it is implemented as a microfluidic device. Such a microfluidic device, or lab-on-a-chip device, can be used in a wide variety of applications for decentralized diagnostics.

[0023] In the method for operating the optical analysis device, a sample is first placed on the sample holder. It is then excited to fluorescence by means of the light source, and the light emitted by the sample is detected by the optical sensor. A fluorescence analysis of the sample can be performed in x • y optical channels using multiplexing.

[0024] Brief description of the drawings

[0025] Exemplary embodiments of the invention are shown in the drawings and are explained in more detail in the following description.

[0026] Figure 1 shows an optical analysis device according to an embodiment of the invention. R. 415711

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[0028] Figure 2 shows the wavelength bands of a first filter carrier used in an optical analysis device according to an embodiment of the invention.

[0029] Figure 3 shows the wavelength bands of a second filter carrier used in an optical analysis device according to an embodiment of the invention.

[0030] Figure 4 shows the interaction of two filter carriers for selecting a wavelength band in a filter device according to an embodiment of the invention.

[0031] Exemplary embodiment of the invention

[0032] An optical analysis device according to an embodiment of the invention is shown in Figure 1. It comprises a filter device consisting of a first filter carrier 10 and a second filter carrier 20. These two filter carriers are designed as filter sliders, which are slidable in the same direction. The first filter carrier 10 has two first optical filters 11, 12. These are designed as a short-pass filter 11 and a long-pass filter 12, or as band-pass filters. The second filter slider 20 has three second optical filters 21 to 23. These are each designed as multiband-pass filters for two wavelength bands, i.e., as double band-pass filters. The two first optical filters 11, 12 are configured such that they are each transparent for one wavelength band of each second optical double band-pass filter 21, 22, 23. Furthermore, the optical analysis device has a filter wheel 30 with four band-pass filters 31 to 34.The filter wheel is arranged in a beam path between a light source 41 and a sample carrier 42. The light source 41 is, for example, a white LED. The filter device is arranged in a beam path between the sample carrier 42 and an optical sensor 43. The first filter carrier 10 faces the sample carrier 42, and the second filter carrier 20 faces the optical sensor 43. A biological sample 50 to be examined is arranged on the sample carrier 42. This sample has been treated with several different fluorophores, which correspond to different pathogens in the biological R. 415711.

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[0034] The light source 41 sends excitation light 61 through one of the bandpass filters 31 to 34 of the filter wheel 30 onto the sample 50. The bandpass filter 31 used limits the wavelength range of the excitation light 61 to a predetermined wavelength band. The excitation light 61 excites at least one of the fluorophores in the sample 50 to fluorescence. The fluorescence light 62 shines through one of the first optical filters 12 and one of the second optical filters 21. The wavelengths of the fluorescence light 62 that pass through these two optical filters 12, 21 ultimately reach the optical sensor 43. The combination of the wavelength band of the excitation light 61 and the wavelength band in which the fluorescence light 62 can pass through the filter pair 12, 21 of the filter device forms an optical channel.By rotating the filter wheel 30 and by moving the two filter carriers 10, 20, the examination of the sample 50 can then be repeated in further optical channels.

[0035] Figure 2 shows in a diagram the wavelengths X at which transmission T of fluorescence light 62 through one of the first optical filters 11, 12 is possible. A first optical filter 11 allows transmission T in a first wavelength band 71, and the other first optical filter 12 of the first filter carrier allows transmission T in a further first wavelength band 72 at longer wavelengths than those allowed by the preceding first optical filter 11. As explained above, the first optical filter is, for example, a short-pass filter 11 or a band-pass filter 12, and the second optical filter is a long-pass filter 12 or a band-pass filter 12, so that, as shown in Figure 2, the wavelength bands for which the two filters 11, 12 are transparent preferably do not overlap.

[0036] Figure 3 shows in a diagram the wavelengths X at which transmission T through the second optical filters 21 to 23 of the second filter carrier 20 is possible. Three second wavelength bands 81 to 83 lie in the wavelength range of the first wavelength band of one of the first optical filters 11 of the first filter carrier 10, and three further second wavelength bands 84 to 86 lie in the wavelength range of the other of the first optical filters 12 of the first filter carrier 10. In other words, the two first optical filters 11, 12 are designed such that only one first optical filter 11, 12 is used. R. 415711

[0037] - 7 - is transparent for each of the second wavelength bands 81 to 86, where in this example each of the first optical filters 11, 12 is transparent for three of the second wavelength bands 81 to 86. Each of the second optical filters 21 to 23 of the second filter carrier 20 allows light to pass through in two of these second wavelength bands 81 to 86. Two second wavelength bands 81, 84 are assigned to one second optical filter 21, two further second wavelength bands 82, 85 are assigned to another second optical filter 22, and two further second wavelength bands 83, 86 are assigned to the last second optical filter 23.

[0038] Figure 4 shows how a first optical filter 12 of the first filter carrier 10 and a second optical filter 21 of the second filter carrier 20 interact in the arrangement shown in Figure 1 when illuminated by fluorescent light 62. First, the fluorescent light 62 falls on the first optical filter 12, which only allows light of its first wavelength band 72 to pass through. This means that fluorescent light 62 of the second wavelength bands 84 to 86, which lie within this first wavelength band 72, can pass through the first optical filter 12. The second optical filter 21 of the second filter carrier 20 then only allows light of its second wavelength band 84 to pass through within this first wavelength band 72. Thus, only fluorescent light 62 with wavelengths within this wavelength band 84 reaches the optical sensor 43.By moving the two filter carriers 10, 20 relative to each other, six different settings are possible, whereby in each setting only light of one of the second wavelength bands 81 to 86 can pass through the two optical filters of both filter carriers 10, 20 positioned in the beam path. Thus, optical channels can be formed using four different excitation light wavelength bands and six different fluorescence light wavelength bands.

Claims

R. 415711 - 8 - Claims 1. Filter device comprising a first filter carrier (10) with x first optical filters (11, 12) and a second filter carrier (20) with y second optical filters (21-23), wherein x and y each have a value of at least 2 independently of one another, and wherein the filter carriers (10, 20) are configured to arrange one filter (11, 12, 21-23) of each filter carrier (10, 20) in a beam path of the filter device, characterized in that each first optical filter (11, 12) allows light (62) of a respective first wavelength band (71, 72) to pass through and each second optical filter (21-23) allows light (62) of x respective second wavelength bands (81-86) to pass through, wherein the first wavelength bands (71, 72) do not overlap, the second wavelength bands (81-86) do not overlap, and in each first wavelength band (71 ,72) each contains a second wavelength band (81 - 86) of each of the second optical filters (21 - 23).

2. Filter device according to claim 1, characterized in that the filter carriers (10, 20) are filter slides.

3. Filter device according to claim 1 or 2, characterized in that x = 2 and y = 3.

4. Optical analysis device comprising a light source (41), a sample carrier (42) and an optical sensor (43), characterized in that a filter device according to one of claims 1 to 3 is arranged in a beam path between the light source (41) and the sample carrier (42) and / or in a beam path between the sample carrier (42) and the optical sensor (43).

5. Optical analysis device according to claim 4, characterized in that in the beam path between the light source (41) and the R. 415711 - 9 - A sample carrier (42) is arranged with a filter wheel (30) and a filter device according to one of claims 1 to 3 is arranged in the beam path between the sample carrier (42) and the optical sensor (43).

6. Optical analysis device according to claim 4 or 5, characterized in that it is designed as a microfluidic device.

7. Method for operating an optical analysis device according to one of claims 4 to 6, wherein a sample (50) is arranged on the sample carrier (42), is excited to fluorescence by means of the light source (41) and light (62) emitted by the sample (50) is detected by the optical sensor (43), wherein a fluorescence analysis of the sample is carried out in x • y optical channels.

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