EP3870942A2

EP3870942A2 - Filter device for an optical module for a lab-on-a-chip analysis device, optical module for a lab-on-a-chip analysis device and method for operating an optical module for a lab-on-a-chip analysis device

Info

Publication number: EP3870942A2
Application number: EP19790509.4A
Authority: EP
Inventors: Jochen Rupp; Robert SCHREINER; Karsten Seidl; Tino Frank; Genrich Siris
Original assignee: Robert Bosch GmbH
Current assignee: Robert Bosch GmbH
Priority date: 2018-10-22
Filing date: 2019-10-18
Publication date: 2021-09-01
Also published as: CA3120147A1; DE102018218046A1; US20220252513A1; WO2020083768A2; JP2022508894A; CN113167647A; WO2020083768A3; KR20210082206A

Abstract

The invention relates to a filter device (130) for an optical module for a lab-on-a-chip analysis device. The optical module comprises a light path. The filter device (130) comprises a support element (205), a filter support (210) and a drive device (215). The support element (205) can be mounted in the optical module (100). The filter support (210) is arranged so that it can move on the support element (205). The filter support (210) also has a first filter region (220) and a second filter region (225). The drive device (215) is designed such that the filter support (210) can move between a first position in which the first filter region (220) is arranged in the light path, and a second position in which the second filter region (225) is arranged in the light path.

Description

description

title

Filter device for an optical module for a chip laboratory analyzer, optical module for a chip laboratory analyzer and method for operating an optical module for a chip laboratory analyzer

State of the art

The invention is based on a device or a method according to the type of the independent claims.

In-vitro diagnostics (IVD) is a field of medical devices that consists of human samples of specific sizes such as a concentration of a molecule

Measure the presence of a specific DNA sequence or composition of blood to allow diagnosis and treatment decisions. This can be done in a chain of several laboratory steps, whereby the sample can be processed so that the target size can be measured without interference. Different laboratory methods can be used with a device suitable for the method. In-vitro diagnostic tests of this type can be mapped in one device in analysis devices for patient-related laboratory diagnostics, so-called point-of-care devices, in order to reduce the number of manual steps by the user. The sample or the sample can be entered into a disposable cartridge. After entering the cartridge into the analyzer, the diagnostic test can be carried out fully automatically. To carry out fluorescence-based detection methods, the analysis device can have optical or opto-mechanical elements.

Disclosure of the invention Against this background, the approach presented here becomes a

Filter device for an optical module for a chip laboratory analyzer

Optical module for a chip laboratory analyzer and a method for operating an optical module for a chip laboratory analyzer according to the main claims presented. The measures listed in the dependent claims allow advantageous developments and improvements of the device specified in the independent claim.

The filter device can advantageously be designed as an opto-mechanical

Device for a chip laboratory analyzer can be used. An electrically driven filter carrier of the filter device enables a quick filter change, which is advantageous with regard to diagnostic methods. The design of the filter device enables various optical detection methods to be implemented, which is advantageous for versatile uses of the chip laboratory analysis device. Advantageously, the

Filter device also a particularly compact design.

A filter device for an optical module for a chip laboratory analysis device is presented. The optics module has a light path. The filter device comprises a carrier element, a filter carrier and a drive device. The carrier element can be arranged in the optical module. The filter carrier is movably arranged on the carrier element. In addition, the filter carrier has a first filter area and a second filter area. The drive device is designed to move the filter carrier between a first position in which the first filter area is arranged in the light path and a second position in which the second filter area is arranged in the light path.

The chip laboratory analysis device can be a device for carrying out a diagnostic method, in which a chip laboratory cartridge is analyzed, which can also be referred to as chip laboratory or microfluidic system. The optics module can be used for optical diagnostics, for example to duplicate DNA using a

Observe fluorescence measurement after each polymerase chain reaction cycle, or for another fluorence-based detection method such as melting curve analysis. The light path of the optics module can be act an excitation light path or a detection light path. The

Excitation light path can lead from a light source to the chip laboratory cartridge. The detection light path can lead from the chip laboratory cartridge to an image sensor. The filter device can be used to filter the light following the light path. Advantageously, time

successively different filter areas of the filter device are positioned in the light path. As a result, different wavelengths of light can be filtered out or transmitted in succession. Two different filters, for example a color filter and a black filter, can be arranged on the first and second filter areas of the filter carrier. Also, no filter can be arranged on one of the filter areas, so that an empty position is realized. With a color filter, at least one wavelength range of light can be filtered out at the corresponding filter range. With a black filter, the light can be completely absorbed at the corresponding filter area. At a

Empty position, the light can pass through the corresponding filter area unfiltered. The drive device can be electrical, for example, and can be designed to change positions of the filter areas. For this purpose, the drive device can, for example, linearly shift or rotate the filter carrier to assume the first and second positions in order to arrange one or more of the filter areas in a light path.

According to one embodiment, the first filter area can be formed as an optical filter or as an empty position. Additionally or alternatively, the second filter area can be shaped as an optical filter or as an empty position. In addition, the filter carrier can also have further filter areas, which can also be shaped as an optical filter or empty position. Forming an empty position is advantageous in order to achieve chemiluminescence detection

enable.

According to one embodiment, the drive device can be designed as a belt drive with a toothed belt and an electric motor. The

Electric motor can be designed as a stepper motor, for example. To the

Moving the filter carrier, the toothed belt can for example be connected to a drive roller which is driven by the electric motor. For tensioners can be used to tighten the toothed belt. Such a drive of the filter carrier makes it possible to change the position of the filter areas and thus change the filter particularly quickly, for example in a time of less than half a second.

According to one embodiment, the filter device can also have a sensor that is designed to provide a sensor signal that represents a positioning of the filter carrier. The sensor can be designed, for example, as a Hall sensor or as a photoelectric sensor. A photoelectric sensor can be one that is known in measurement technology

Implement transmitted light process or incident light process. The sensor can be designed to detect the position of the filter areas of the filter carrier or a movement of the filter carrier. This advantageously enables exact monitoring of the position of the filter carrier and thus of the filter areas and of filters arranged in the filter areas. The sensor signal can be used, for example, to control the drive device, the light source and / or the image sensor.

According to one embodiment, the filter carrier can be designed as a linearly movable filter slide or as a rotatable filter wheel. The design as a linearly movable filter slide, also called a slider, enables this

Advantageously minimized travels of the filter carrier when moving the filter carrier relative to the carrier element in order to adjust the position of the filter areas. The design as a filter wheel is advantageous, for example, if the filter device is arranged in an excitation light path for fluorescence excitation.

If the filter carrier is designed as a linearly movable filter slide, the filter device can have a further filter slide. The further filter slide can be arranged movably on the carrier element. In addition, the further filter slide can have a further first filter area and a further second filter area. The drive device can be designed to move the further filter slide between a further first position in which the further first filter area is arranged in the light path and a further second position in which the further second filter area in the light path is arranged to move. The filter slide and the further filter slide can be arranged partially overlapping, which is advantageous in terms of a compact design.

The optical module for the chip laboratory analysis device can have a further light path. In this case, according to one embodiment, in the first position of the filter slide, the first filter area can be arranged in the light path and the second filter area in the further light path. Additionally or alternatively, in the further first position of the further filter slide, the further first filter area can be arranged in the light path and the further second filter area in the further light path. In addition, depending on the arrangement of the filter areas on the filter slide and the further filter slide in the first position of the filter slide, the first filter area can be arranged in the light path and the second filter area in the further light path or outside the light path and outside the further light path. Furthermore, in the second position of the filter slide, the second filter area can be arranged in the light path and the first filter area in the further light path or outside the light paths. It is therefore advantageously possible to optically influence several light paths separately.

According to one embodiment, the filter slide and the further filter slide can also be arranged at least in sections one above the other and can be displaced in relation to one another in translation. For this, the

The filter slide and the further filter slide can be arranged, for example, in a translatory manner on rails mounted on ball bearings. This arrangement is related to a quick filter change from at the filter areas

arranged filters and in relation to the smallest possible width of the

Filter device an advantage.

If the optical module has a further light path and the filter carrier is designed as a filter wheel, the filter device can have a further filter wheel according to one embodiment. The further filter wheel can be rotatably arranged on the carrier element. In addition, the further filter wheel can have a further first filter area and a further second filter area. The drive device can be designed for the further filter wheel to move between a further first position in which the further first filter area is arranged in the further light path and a further second position in which the further second filter area is arranged in the further light path. The implementation of a further filter wheel is advantageous if the filter device is arranged in the excitation light path for fluorescence excitation, for example if a cartridge with a plurality of chambers is accommodated in the optics module, which are excited separately.

According to one embodiment, if the filter device comprises the filter wheel and the further filter wheel, the filter wheels can be arranged side by side and can be rotated synchronously. This design enables a quick and uniform filter change, which is more advantageous when optically stimulating several areas at the same time.

This approach also introduces an optics module for a chip lab analyzer. The optics module comprises a light source, a receiving area for a chip laboratory cartridge, an image sensor, an embodiment of a first filter device and an embodiment of a second filter device. The first filter device is arranged in an excitation light path between the light source and the recording area. The second filter device is arranged in a detection light path between the recording area and the image sensor.

The optical module can be used, for example, for fluorescence excitation in a plurality of fluorescence wave areas in one or more areas or chambers of a chip laboratory cartridge accommodated in the recording area. In addition, the optical module can be used for fluorescence detection in several fluorescence wave areas over an image area. It is advantageously possible to enable a quick filter change in, for example, half a second.

If a chip laboratory cartridge is accommodated in the recording area, the fluorescence excitation can take place by means of a white light-emitting diode as the light source. The light-emitting diode can be temperature-stabilized, for example, and monitored for intensity using a control photodiode. An emitted light path can be called the excitation light path. The excitation light path can be directed in the direction of the first filter device; the first filter device can, for example, include the filter carrier in the form of the filter wheel. The excitation light path can be directed to a region of the chip laboratory cartridge to be excited by the first filter device and reflect or fluoresce on the chip laboratory cartridge. The emitting light can be directed as a detection path to the second filter device

can include the filter slide, for example as a filter carrier. From there, the detection light path is directed towards the image sensor. The image sensor can comprise a macro lens, for example.

A method for operating an embodiment of the optical module for a chip laboratory analysis device described above is also presented. The method comprises a step of providing a first setting signal, a step of providing a second setting signal, a step of providing a first filter change signal and a step of providing a second filter change signal. The first

Setting signal is designed to set the filter carrier of the first filter device in a position assigned to an analysis mode. The position assigned to the analysis mode can be, for example, the first position or the second position of the filter carrier. The second setting signal is designed to set the filter carrier of the second filter device in a position assigned to the analysis mode. The first

Filter change signal is designed to the filter carrier of the first

Set the filter device in a position assigned to a further analysis mode. The second filter change signal is designed to set the filter carrier of the second filter device in a position assigned to the further analysis mode. For example, the other

Analysis mode assigned position of the filter carrier of the first

Filter device, the position of the filter carrier corresponding to the analysis mode corresponding to the first filter device, in this case the set position of the filter carrier is not changed.

Embodiments of the approach presented here are shown in the drawings and explained in more detail in the following description. It shows: Figure 1 is a schematic representation of an optical module for a chip laboratory analyzer according to an embodiment.

FIGS. 2 to 4 each show a schematic representation of a filter device for an optical module for a chip laboratory analysis device according to an exemplary embodiment;

Fig. 5 is a schematic representation of an assembly with a

Filter device for an optical module for a chip laboratory analysis device according to an embodiment;

6 shows a schematic illustration of a filter device for an optical module for a chip laboratory analysis device according to an exemplary embodiment;

7 shows a schematic illustration of part of an optical module for a chip laboratory analysis device according to an exemplary embodiment;

8 shows a schematic illustration of part of a filter device for an optical module for a chip laboratory analysis device according to an exemplary embodiment;

9 shows a schematic illustration of a part of an optical module for a chip laboratory analysis device according to an exemplary embodiment;

10 shows a schematic illustration of a chip laboratory analysis device with an optical module according to an exemplary embodiment;

11 shows a flowchart of a method for operating an optical module for a chip laboratory analysis device according to an exemplary embodiment;

12 shows a schematic illustration of the use of an optical module for a chip laboratory analysis device according to an exemplary embodiment; and

13 shows a schematic illustration of the use of a chip laboratory analysis device with an optical module according to an exemplary embodiment. In the following description of advantageous exemplary embodiments of the present invention are shown in the various figures

illustrated and similarly acting elements same or similar

Reference numerals are used, a repeated description of these elements being omitted.

1 shows a schematic illustration of an optics module 100 for a chip laboratory analysis device according to an exemplary embodiment. The optical module 100 comprises a light source 105, a receiving area 110 for a chip laboratory cartridge 115, an image sensor 120, a first filter device 125 and a second filter device 130. The first filter device 125 is in one

Excitation light path 135 is arranged between light source 105 and receiving area 110. The second filter device 130 is arranged in a detection light path 140 between the recording area 110 and the image sensor 120.

The optics module 100 can also be referred to as a fluorescence optics module or as an optofluid analysis platform for in-vitro diagnostics. A chip laboratory cartridge 115 is arranged, for example, in the receiving area 110. The light source 105 is designed, for example, as a white light-emitting diode. By means of a guide cone 145 as a light guide, the light emitted by the light source 105 is guided to the first filter device 130, and then to an excitation area on the chip laboratory cartridge 115. The chip laboratory cartridge 115 has a chamber with a reaction liquid. For example, fluorescence excitation takes place in the reaction liquid in the chamber that corresponds to the excitation area. The emitted fluorescent light is then guided along a detection light path 140 to the second filter device 130 and imaged on the image sensor 120 by means of an optional macro lens 150.

A color filter, which is designed to filter a corresponding detection wavelength, is optionally arranged in the second filter device 130. In this way, wavelengths to be detected can pass through the filter device 130. The optics module can also have a plurality of light sources 105. In this case, the first filter device 125 and the second filter device 130 are shaped accordingly in order to filter or block light from a plurality of light paths conduct. Monochromatic filters, for example, are arranged on the filter devices 125, 130.

The image sensor 120 can be implemented, for example, as a CMOS detector with a larger recording field than the one or more light sources 105 is covered. The optics module 100 shown here can be used for controls, initial tests and different detection methods as well as for different recording modes and combinations of different recording modes, which is described in more detail with reference to the following figures. Advantageously, this makes it possible to implement 100 different detection methods despite the compact design of the optical module. Thanks to its modular structure, the optics module 100 offers clear design rules and

Interface requirements a high implementation variation. In addition, it is advantageously possible to use feedback systems and dynamic

Implement step sequences. Depending on the structure of the optical module 100, for example with a plurality of light sources 105 and correspondingly shaped filter devices 125, 130, it is also possible to run and record processes in parallel. For example, various

Control recordings made in the same or a different recording mode before the actual signal is measured. A control can thus be a spatially resolved image, while the actual measurement is an averaged value. In the case of irregularities, the detection mode can be changed in order to assess errors directly, as described with reference to FIG. 13.

The optical module 100 shown here can be used in conjunction with the chip laboratory analysis device for executing a measurement method such as a polymerase chain reaction (PCR), a fluorescence measurement or a pH measurement, in particular for evaluating various biochemical ones

Diagnostic methods that are fluidically processed and analyzed using a microfluidic system such as the chip laboratory cartridge 115 shown here as an example, also referred to as chip laboratory or lab-on-chip. The optical module 100 can be used, for example, to carry out a quantitative PCR (qPCR) or also real-time qPCR, in which a duplication of the DNA is observed by means of a fluorescence measurement after each PCR cycle. DNA dyes are used to detect and quantify the PCR products used. Another fluorescence-based method is the melting curve analysis, in which the DNA double strand is melted at a DNA sequence specific temperature. In doing so, a

Fluorescent dye released and a change in the fluorescence signal is detectable. The temperature is gradually passed in tenths of a degree in areas between 20 - 95 ° C, for example, and after each temperature step or during the temperature increase, the fluorescence should be measured. The use of different dyes makes multiplex tests for the detection of different DNA sequences (both with qPCR as well as melting curve or other fluorescence-based

Detection method). By means of the optical module 100 shown here, it is advantageously possible to read out the fluorescence of different dyes in a short time, for example within a few seconds, in the smallest installation space.

The arrangement of optical filter elements on the filter devices 125, 130 in the excitation light path 135 and detection light path 145 of fluorescent optics, as well as the shaping of the filter devices 125, 130, which is described in more detail with reference to the following FIGS. 2 to 5, is made possible

advantageously to achieve filter change times between two filter elements of an average of half a second, so that cycle times of less than six and a half seconds for four colors, including the image acquisition times of the image sensor 120, are possible. The fluorescence detection is carried out by means of the image sensor 120, for example over a large detection area of larger than 20 × 20 square millimeters. Depending on the structure of the optical module, the fluorescence excitation potentially takes place in several chambers of the chip laboratory cartridge 115, each with a diameter of at least 2 millimeters.

The width of the optical module 100 is less than 200 millimeters, for example. An image analysis of the recorded fluorescence image is carried out, for example, using image processing algorithms. A reagent chamber for position detection of the chamber within the image and / or a liquid plug detection and analysis can be carried out.

FIG. 2 shows a schematic illustration of a filter device 130 for an optical module for a chip laboratory analysis device according to an exemplary embodiment. The filter device 130 shown here is similar or corresponds to the second filter device described with reference to FIG. 1. The optics module has at least one light path. According to the exemplary embodiment shown, the filter device 130 has a through opening 201 for a light path and an optional further through opening 202 for a further light path. For example, the filter device 130 has a length of less than 250 millimeters and a width of less than 100 millimeters.

The filter device 130 has a carrier element 205, a filter carrier 210 and a drive device 215. The carrier element 205 can be arranged in the optics module. The filter carrier 210 is movably arranged on the carrier element 205. In addition, the filter carrier 210 has at least a first one

Filter area 220 and a second filter area 225, here the

Filter carrier also has, for example, a third filter area 230. The

Drive device 215 is designed to move the filter carrier 210 between a first position in which the first filter region 220 is arranged in the light path and a second position in which the second filter region 225 is in the

Light path is arranged to move. If the light path is guided through the first through opening 201, for example, the filter carrier 210 is shown here in the first position.

According to the exemplary embodiment shown here, the drive device 215 is designed as a belt drive with a toothed belt 235 and an electric motor. For example, the electric motor can be a stepper motor, too

Be called stepper motor. By means of the toothed belt 235 it is possible to move the filter carrier 210 quickly and to position it exactly. Additional tensioning rollers 237 are used to tighten the toothed belt 235.

According to the exemplary embodiment shown here, the filter carrier 210 is designed as a linearly movable filter slide. The filter carrier 210, which can be moved by means of the drive device 215, can correspondingly be moved along a section of the toothed belt 235, for example for setting the first, the second or a further position of the filter carrier. In addition to the filter carrier 210 as a filter slide, the filter device 130 according to the exemplary embodiment shown here has an optional further filter slide 240. The further filter slide 240 is movably arranged on the carrier element 205. The further filter slide 240 also has a further first filter area and a further second filter area. In the position shown here of the filter carrier 210 as a filter slide and the further filter slide 240, the further first filter area lies below the first filter area 220 and the further second filter area lies below the second filter area 225 another first position, in which the further first filter region is arranged in the light path, and a further second position, in which the further second filter region is arranged in the light path.

In addition, the filter carrier 210 as a filter slide and the further filter slide 240 according to the exemplary embodiment shown here are arranged at least in sections one above the other. In addition, the filter slide 210 and the further filter slide 240 can be displaced relative to one another in translation. In this way it is possible to shift one of the filter areas 220, 225, 230 or the other filter areas into the light path. It is also possible to combine the filter areas 220, 225, 230 with the other filter areas. In this case, both the filter areas 220, 225, 230 and the further filter areas can be shaped as optical filters or as an empty position according to one exemplary embodiment, as a result of which, for example, chemiluminescence in the optical module by means of the filter device 130 shown here

Chip laboratory analyzer is detectable.

According to this exemplary embodiment, the optical module has the further one

Light path on. In the first position of the filter slide 210 is the first

Filter area 220 in the light path running through the passage opening 201 and the second filter area 225 in that through the further one

Through opening 202 extending further light path arranged. Additionally or alternatively, in the further first position of the further filter slide 240, the further first filter region is arranged in the light path and the further second filter region in the further light path. In an assembled state of the filter device 130 and the optical module, it is thus possible to excite fluorescence in several

To carry out fluorescence wave regions in one or more regions or chambers of a chip laboratory cartridge accommodated in the optical module, and then to carry out fluorescence detection in several

To allow fluorescence wave areas over an image area.

Filters can be changed from filters arranged in the filter carrier or the additional filter slide 240 by means of the drive device in an average of half a second. For this purpose, the filter carrier 210 as

The filter slide and the further filter slide 240 are displaced in relation to one another in order to push a color filter received in one of the filter areas 220, 225, 230 or the further filter areas into an image area in order to enable detection by means of the image sensor of the optical module. Each filter slide 210, 240 contains at least one color filter and an empty position. According to one embodiment, the filter slides 210, 240 are shaped to slide translationally on ball-bearing rails. This enables maintenance-free operation of the filter slides 210, 240 with more than two and a half million filter changes. The position of the filter slide 210, 240 is detected and monitored by means of a sensor. In this way, minimized travels of the filter slide 210, 240 are made possible during a sequential movement of all filter elements.

3 shows a schematic illustration of a filter device 130 for an optical module for a chip laboratory analysis device according to an exemplary embodiment.

It is a top view of the embodiment shown in FIG

Filter device shown, is accordingly arranged on the carrier element 205, the filter carrier 210 as a linearly movable filter slide, and the

Filter device 130 includes the further filter slide 240 and the

Drive device 215 as a belt drive. According to what is shown here

In the exemplary embodiment, the filter slide 210 and the further filter slide 240 are driven separately by the toothed belt 235 with an electric motor on a drive roller 305, also called pulley. The position of the filter slide 210 and the further filter slide 240 is in accordance with that shown here

Embodiment monitored by means of a photoelectric sensor 310. For example, the photoelectric sensor 310 is arranged on a side wall of the carrier element 205, different positions of the filter slides 210, 240 being assigned different distances from the photoelectric sensor 310.

In addition, the first filter area 220 is in accordance with that shown here

Embodiment shaped as an optical filter 315 or as an empty position 320. Additionally or alternatively, the second filter area 225 is designed as an optical filter 315 or as an empty position 320. Here, for example, the first filter area 220 and the second filter area 225 are shaped as optical filters, and the third filter area 230 is shaped as an empty position. A filter recess is left free, for example, for shaping the empty position 320, and the optical filter 315 is arranged on the filter recess for shaping one of the filter regions 220, 225, 230 as an optical filter 315. If, in a state connected to the optical module, the filter slide 210 is positioned such that the optical filter 315, for example a color filter, arranged in the first filter area 220 is arranged in the image area, that is to say in the light path, then the further filter slide 240 is arranged in this way, for example that the empty position 320 lies below the first filter area 220. If one of the filter slides 210, 240 is positioned at the position of the optical filter 315 as a color filter in the image area, the other filter slider 210, 240 is in the position of the empty position. If both filter slides 210, 240 are set to the empty position and the area of the chip laboratory cartridge to be detected is not illuminated by the excitation light path, chemiluminescence detection, a self-illuminating reaction, can be detected. If both filter slides 210, 240 are in the empty position 320 and a different excitation wavelength is activated in the excitation path, a control image of the entire image area can be recorded.

FIG. 4 shows a schematic illustration of a filter device 125 for an optical module for a chip laboratory analysis device according to an exemplary embodiment. The filter device 125 shown here is similar or corresponds to the first filter device described with reference to FIG. 1. According to the exemplary embodiment shown here, the filter carrier 210 is designed as a rotatable filter wheel and is also referred to below as a filter wheel 210. In addition, the Filter device 125 according to the embodiment shown here an optional additional filter wheel 405. The further filter wheel 405 has a further first filter area 410 and a further second filter area 415. The filter wheel 210 and the further filter wheel 405 each have a third and a fourth filter area, for example. The drive device 215 is designed to move both the filter wheel 210 and the further filter wheel 405. The drive device 215 is thus designed to move the further filter wheel 405 between a further first position in which the further first filter region 410 is arranged in the further light path and a further second position in which the further second filter region 415 is arranged in the further light path is to move.

According to the exemplary embodiment shown here, the filter wheels 210, 405 are arranged lying side by side in one plane. In addition, the filter wheel 210 and the further filter wheel 405 by means of the toothed belt 235

Drive device 215 rotatable synchronously.

According to the exemplary embodiment shown here, filter wheel 210 and further filter wheel 405 each have four filter areas 405, 410, on which optical filters are arranged as excitation filters. In addition, the filter wheels 210, 405 each have a black position in order to switch the light of the

Block light source, for example a white-emitting excitation light-emitting diode, e.g. to enable dark or noise images to be recorded, or to carry out chemiluminescence detection.

Advantageously, the shape of the filter device 125 shown here enables a compact design with a width of, for example, less than 200 millimeters, with the possibility of forming five filter areas per filter wheel 210, 405 as shown here. For example, it is also possible to arrange six filter positions per filter wheel 210, 405 with two excitation areas on the chip laboratory cartridge with a diameter of more than 2 millimeters

Diameter. An arrangement of the filter device 125 shown here with the drive device 215 in the excitation light path of the optical module advantageously enables a filter change of on average less than half a second. Fig. 5 shows a schematic representation of an assembly with a

Filter device 125 for an optical module for a chip laboratory analysis device according to an exemplary embodiment. In addition to the filter device 125, which is similar or corresponds to the filter device described with reference to FIG. 4, the assembly includes two light sources 105 arranged in the form of light-emitting diodes on the filter device 125. On a side facing the filter device 125, each light source 105 comprises a light guide. The mechanical components of the assembly for the optical module shown here are made of plastic and aluminum, for example. The components are also anodized in black or black to minimize reflection and penetration of light.

The two light sources 105 can be realized, for example, as white light sources, which are temperature-stabilized and monitored for intensity by means of a control photodiode. In order to excite several areas or chambers of the chip laboratory cartridge, a plurality of light sources 105 and filter wheels 210, 405 are correspondingly arranged next to one another, here two as examples. For quick filter change, the filter wheels 210, 405 are by means of the

Drive device 215 moves in the form of the belt drive. The light from the white light-emitting diodes of the light sources 105 is optionally guided by means of light guides to the filters and the excitation area on the chip laboratory cartridge.

The filter device 125 includes according to that shown here

Embodiment also a sensor 510. The sensor 510 is designed here as an example as a photoelectric sensor. In addition, the sensor 510 is designed to provide a sensor signal that represents a positioning of the filter carrier. The sensor signal can be used to control the

Drive device 215 will be used. In addition, the

Filter device 125, the filter carrier 210 designed as a filter wheel and the further filter wheel 405, which are rotatably arranged on the carrier element 205.

FIG. 6 shows a schematic illustration of a filter device 125 for an optical module for a chip laboratory analysis device according to an exemplary embodiment. The filter device 125 shown here is similar or corresponds to the filter devices described with reference to FIGS. 4 and 5. The filter carrier 210 as a filter wheel and the additional filter wheel 405 each have five filter areas, one of which is implemented as a so-called black position for blocking light and four as optical filters. The optical filters are designed here, for example, as excitation color filters and are positioned centrally on the filter wheels 210, 405 and firmly glued into the filter wheels 210, 405. The filter areas and thus the color filters are positioned in the filter carrier 210 as a filter wheel and the further filter wheel 405 in such a way that the same color filter is positioned in both fields and two positions can be excited simultaneously on the chip laboratory cartridge. For example, the color filters have the colors black, gray, red, orange and blue.

FIG. 7 shows a schematic illustration of part of an optical module for a chip laboratory analysis device according to an exemplary embodiment. As part of the

Optics module, two light sources 105 are shown as examples. To each of the

Light sources 105, a light guide 705 is arranged, which is shaped conical. In addition, two lenses 710 are shown, one of which is arranged at an end of each light guide 705 facing away from the light source 105. The part of the optics module shown here also includes a section of the filter carrier 210 as a filter wheel and of the further filter wheel 405

Filter carrier 210 as the filter wheel and the further filter wheel 405 are each arranged on an end of the lens 710 facing away from the light guide 705.

According to the exemplary embodiment shown here, the optical module comprises more than one light source 105. Here, for example, two light-emitting diodes are arranged in parallel as light sources 105, each with one of the funnel-shaped light guides 705 and one of the lenses 710. The filter wheels 210, 405 are set in such a way that they are by means of Communicate gears with each other. A motor gear moves both

Filter wheels 210, 405 simultaneously, as shown in FIG. 8 below.

These subunits are combined after the filter wheels 210, 405 and share the same relay lens. However, the beam paths are locally resolved by the lens 710 in the funnel of the light guide 705. The subunits are symmetrical to each other, but can also be implemented asymmetrically. The arrangement of the light sources 105 results from the structure and the

Toothing of the filter wheels 210, 405. FIG. 8 shows a schematic illustration of part of a filter device 125 for an optical module for a chip laboratory analysis device according to one

Embodiment. The arrangement of the filter carrier 210 as a filter wheel and the further filter wheel 405 from the part of the filter device 125 for the optical module described with reference to FIG. 7 is shown. According to the exemplary embodiment shown here, the drive device 215 comprises a motor gear 805. The motor gear 805 is designed to synchronously rotate the filter carrier 210 as a filter wheel and the further filter wheel 405 in order to adjust the position of the filter areas on the filter carrier 210 and the further filter wheel 405. In this case, teeth of motor gear 805 engage directly in gear rings of filter wheels 210, 405. In this way, a toothed belt can be dispensed with.

9 shows a schematic illustration of a part of an optical module for a chip laboratory analysis device according to an exemplary embodiment. As part of the

Optics module shows a total field of view 905 of a camera or the image sensor of the optics module in combination with the macro lens. By means of a

Exposure unit, which comprises the light sources, which are based on the

Similar to or correspond to the previous figures described light sources, two homogeneous spots 910, 911 are generated. The spots 910, 911 correspond to areas of the chip laboratory cartridge accommodated in the optical module, which are illuminated by means of the light sources 105. The spots 910, 911 have a homogeneous illumination in the indicated spot regions. If you are working in a fluorescence mode, the corresponding fluorophores are visible there. If you choose an analysis filter, more of the surroundings can be seen through scattered light and the entire total field of view 905 can also be observed. In addition, spots 910, 911 show areas in which quantitative fluorescence measurements are possible. Quantitative absorption measurements are also possible in this area. For reflected light images, where local resolution is required, this can be achieved by high exposure times and stray light. The desired recording area, the field of view to be measured (English Region of Interest [ROI]) can be selected via software. The one you want

Theoretically, the recording area moves between a pixel and the total field of view 905. The dynamic field of view selection can be used to reduce the amount of data, so that the entire field of view 905 does not have to be stored and sent as a data packet. An image can be used in software can also be constructed from a combination of different desired recording areas (ROI) from different recordings.

10 shows a schematic illustration of a chip laboratory analysis device 1000 with an optics module 100 according to an exemplary embodiment. In the chip laboratory analyzer 1000 is a chip laboratory cartridge 115 in the form of a

Disposable microfluidic unit arranged. Chemical and fluidic channels are located on the chip laboratory cartridge 115. Control, condition, function and detection units are integrated in the chip laboratory analyzer 1000 in the form of fixed interfaces, for example between the optics module 100 and the chip laboratory cartridge 115. A central control unit 1005 orchestrates all other units of the chip laboratory analyzer 1000. This is the

Control unit 1005 capable of signal transmission connected to the following units of the chip laboratory analysis device 1000: the optical module 100, which is also designed as a central detection unit, an acoustic unit 1010 that can generate or measure sound waves, a temperature unit 1015, a user interface 1020, a pneumatic unit 1025 and a library 1030 with various pieces of software, e.g. an assay specific

Evaluation algorithm and a data storage. The control unit 1005 processes an assay-specific protocol of predefined steps. The control unit 1005 activates the corresponding units in a time-controlled process. The control unit mainly sends out commands. However, it is also possible for the control unit 1005 to receive data as a response, to evaluate it, and then to decide on a continuation in the assay protocol and to adapt the protocol dynamically.

In addition to a system such as the embodiment shown here

Chip laboratory analyzer 100 with the capacity to process a microfluidic unit such as the chip laboratory cartridge 115 shown here, it is possible to create a scaled system with the same architecture and the capacity to process several microfluidic units. Each microfluidic unit can have its own identical optical unit in the form of the optical module 100. Alternatively, the microfluidic units can be arranged in such a way that the optics module 100 by means of a motorized xy- Stage, i.e. a frame that can be moved in two directions, is moved back and forth and serial images are recorded.

11 shows a flowchart of a method 1100 for operating an optical module for a chip laboratory analysis device according to an exemplary embodiment. The method 1100 shown here can be used to do one of the above

to operate the described embodiment of the optical module. The

Method 1110 comprises a step 1105 of providing a first setting signal, a step 1110 of providing a second

Setting signal, a step 1115 of providing a first

Filter change signal and a step 1120 of providing a second filter change signal. The first setting signal in step 1105 is designed to set the filter carrier of the first filter device in a position assigned to an analysis mode. The position assigned to the analysis mode can be, for example, the first position or the second position of the filter carrier, as described above with reference to FIGS. 2 and 3. The second setting signal in step 1110 is configured to the filter carrier of the second filter device in an analysis mode

set assigned position. The first filter change signal in step 1115 is designed to set the filter carrier of the first filter device in a position assigned to a further analysis mode. The second

The filter change signal in step 1120 is designed to set the filter carrier of the second filter device in a position assigned to the further analysis mode.

An exemplary embodiment of the method 1100 and thus an exemplary setting and filter change possibility of the first and second filter device of the optical module is explained below using various modes for image recordings: In an analysis mode “blocked”, the light path is from the direction of the light unit and in the direction covered by the detection unit, the filter supports of the first filter device, also called filter LED, and of the second filter device, also called filter camera, are accordingly in a “shutter position”. The “blocked” analysis mode is used, for example, to measure noise from a CMOS chip (Salt and Pepper Noise). In an analysis mode "no light is not filter or an analysis filter placed in front of the LED and camera. In front of the LED, various LED filters can also be recorded one after the other and summed up accordingly. In the analysis mode "reflected light is in the illuminated

An analysis or excitation filter is arranged correspondingly to the filter area of the filter carrier of the first filter device, and an analysis filter or no filter insert is arranged in the illuminated filter area of the filter carrier of the second filter device. For fluorescence, the corresponding

Excitation and emission filters set. In an analysis mode “fluorescence”, an excitation filter is the first in the corresponding filter area

Filter device and an emission filter in the filter area of the second

Filter device arranged. For a chemiluminescence measurement, the light source is blocked and the analysis filter is used. In a “chemiluminescence” analysis mode, there is a “shutter” in the corresponding filter area of the first filter device, and an analysis filter or no filter insert in the filter area of the second filter device. These modes can be combined with dynamic fields of view (Rol).

12 shows a schematic illustration of the use of a

Optical module for a chip laboratory analysis device according to an embodiment. Combinations of different recording modes with different fields of view are shown in one sequence of the method. The first recording mode 1205 shows an example of a total field of view. For example, a position of the microfluidic unit, ie the chip laboratory cartridge, can be checked. With this information, a relative coordinate system can be created for the chip laboratory cartridge. This is of interest since, due to manufacturing and mechanical conditions, each chip laboratory cartridge can lie slightly shifted in the analysis unit, the chip laboratory analyzer. This information must be measured once and the ROI for subsequent recordings with the same chip laboratory cartridge can be dynamically adjusted. Such a picture can also be used to determine whether fluids are present in microfluidic channels. A second recording mode 1210 shows how an assay result can be read out by fluorescence. In a next step, when the first measuring method of the first part has been completed and the sample is processed further, an image recording in transmitted light mode, as shown by means of a third recording mode 1215, can be used to check whether the Transition from the first method to the second has been successful, or whether, for example, air has entered the system or has not been mixed. In the next step, the second method can then use a different recording mode, a fourth recording mode 1220 shown here

be included. In all steps can be different

Filter positions and fields of view can be recorded with the same optical unit, the optical module. As an example, an assay is listed here in which, in a first step, sample material is cleaned up, amplification takes place by means of PCR and the specificity of the PCR products is detected by means of a DNA microarray. In addition to the universal situation picture, it can also be repeatedly measured in the bright field whether bubbles are in the analyte. A PCR can then be followed using fluorescence. For example in real time or with a start and end point measurement. The microarray can then be read out by means of chemiluminescence. Microarrays, which are often spatially separated from PCR reaction vessels, can simply be arranged on a chip laboratory cartridge according to the described arrangement of the analysis unit system and connected by means of channels.

FIG. 13 shows a schematic illustration of the use of a chip laboratory analysis device with an optical module according to an exemplary embodiment. In this case, for example, a chip laboratory analysis device is used, as is described with reference to FIG. 10. As an example, use of the chip laboratory analyzer for dynamic progress monitoring of a LoC assay is shown here. For this purpose, a recording mode 1305 shown here is recorded. An evaluation then takes place, here marked by a first block 1310. If a quantitative measurement, e.g. a fluorescence measurement is carried out, then the result is evaluated in situ. If the signal corresponds to the assay according to the usual values, the test procedure or measurement is continued, and the test continues accordingly

Record mode 1305 executed. If an anomaly is found in the measured value, the measurement field is analyzed in another analysis mode 1315, e.g. Incident light instead of fluorescence, measured to analyze what led to the anomaly. There is a deviation measurement and a comparison with known anomalies, here marked by a second block 1320. The

Deviation measurement is done with a library of possible errors adjusted. Each assay has different causes for an anomaly. These can be checked and analyzed using different recording modes. The error analysis can then be compared with the library and a corresponding error message can be returned, here marked by a third block 1325 “error code”. Is the mistake in the

If the library is not noted, it can also be sent back to a platform provider via communication interfaces, analyzed and added to the library as a new element. The method is then continued according to instructions from the library corresponding to the error message, which is marked here by a fourth block 1330.

If an exemplary embodiment comprises an “and / or” link between a first feature and a second feature, this is to be read in such a way that the exemplary embodiment according to one embodiment has both the first feature and the second feature and according to a further embodiment either only that has the first feature or only the second feature.

Claims

Expectations

1. Filter device (125, 130) for an optical module (100) for a chip laboratory analysis device (1000), the optical module (100) having a light path, the filter device (125, 130) having the following features: a carrier element (205) that can be arranged in the optical module (100); a filter carrier (210) which is movably arranged on the carrier element (205) and has a first filter region (220) and a second filter region (225); a drive device (215) which is designed to move the filter carrier (210) between a first position in which the first filter region (220) is arranged in the light path and a second position in which the second filter region (225) in the Light path is arranged to move.

2. Filter device (125, 130) according to claim 1, wherein the first

Filter area (220) and / or the second filter area (230) is formed as an optical filter (315) or as an empty position (320).

3. Filter device (125, 130) according to one of the preceding

Claims, wherein the drive device (215) is designed as a belt drive with a toothed belt (235) and an electric motor.

4. Filter device (125, 130) according to one of the preceding

Claims, with a sensor (310; 510), which is designed to represent a positioning of the filter carrier (210)

Provide sensor signal.

5. Filter device (125, 130) according to one of the preceding claims, wherein the filter carrier (210) as a linearly movable

Filter slide or is designed as a rotatable filter wheel.

6. Filter device (125, 130) according to one of the preceding

Claims, wherein the filter carrier (210) as a linearly movable

Filter slide is designed and with a further filter slide (240) which is movably arranged on the carrier element (205) and has a further first filter area and a further second filter area, wherein the drive device (215) is designed to the further filter slide (240) to move between a further first position in which the further first filter area is arranged in the light path and a further second position in which the further second filter area is arranged in the light path.

7. The filter device (125, 130) according to claim 6, wherein the optical module (100) has a further light path, wherein in the first position of the filter slide, the first filter area (220) in the light path and the second filter area (225) in the further light path is arranged and / or in the further first position of the further

Filter slide (240) the further first filter area is arranged in the light path and the further second filter area is arranged in the further light path.

8. Filter device (125, 130) according to one of claims 6 or 7, wherein the filter slide and the further filter slide (240) are arranged at least in sections one above the other and are translationally displaceable against each other.

9. Filter device (125, 130) according to one of claims 1 to 5, wherein the optics module (100) has a further light path, wherein the filter carrier (210) is designed as a filter wheel and with a further filter wheel (405) which is rotatable on the Carrier element (205) is arranged and has a further first filter area (410) and a further second filter area (415), the drive device (215) being designed to place the further filter wheel (405) between a further one first position, in which the further first filter area (410) is arranged in the further light path, and a further second position, in which the further second filter area (415) is arranged in the further light path.

10. The filter device (125, 130) according to claim 9, wherein the filter wheels (405) are arranged side by side and can be rotated synchronously.

11. Optics module (100) for a chip laboratory analysis device (1000), the optics module (100) having the following features: a light source (105); a receiving area (110) for a chip laboratory cartridge (115); an image sensor (120); a first filter device (125) according to one of the preceding claims, which is arranged in an excitation light path (135) between the light source (105) and the receiving region (110); and a second filter device (130) according to one of the preceding claims, which is arranged in a detection light path (140) between the recording region (110) and the image sensor (120).

12. Method (1100) for operating an optical module (100) for a

The chip laboratory analyzer (1000) according to claim 11, wherein the method (1100) comprises the following steps:

Providing (1105) a first setting signal, which is designed to set the filter carrier (210) of the first filter device (125, 130) in a position assigned to an analysis mode;

Providing (1110) a second setting signal which is designed to set the filter carrier (210) of the second filter device (125, 130) in a position assigned to the analysis mode; Providing (1115) a first filter change signal, which is designed to set the filter carrier (210) of the first filter device (125, 130) in a position assigned to a further analysis mode; and

Providing (1120) a second filter change signal, which is designed to set the filter carrier (210) of the second filter device (125, 130) in a position assigned to the further analysis mode.