Automated PCR analyzer

Abstract

An automated polymerase chain reaction (PCR) analyzer (110) for analyzing at least one sample (112) and a method of automated PCR analysis is disclosed. The automated PCR analyzer (110) comprises: - at least one controller (114); - at least one thermocycling apparatus (116) configured for subjecting the sample (112) to at least one temperature modulation controlled by the controller (114); and - at least one photometer (118) configured for detecting at least one optically detectable property of the sample (112), the photometer (118) comprising at least one excitation light source (120) configured for illuminating the sample (112) with excitation light (122), the photometer (118) further comprising at least one photodetector unit (124) configured for detecting light (123) emitted from the sample (112), the photometer (118) further comprising a movable filter cell (126) controllable by the controller (114), the movable filter cell (126) comprising a plurality of filter cell units (128), each filter cell unit (128) comprising at least one optical excitation filter element (130), at least one dichroic filter (132), at least one optical detection filter element (134) and at least one the aperture stop (174), wherein the photometer (118) comprises a working position for the filter cell units (128), wherein the movable filter cell (126) is configured for selectively positioning a selected filter cell unit (128) selected from the plurality of filter cell units (128) in the working position, wherein, in the working position, the selected filter cell unit (128) is positioned such that the excitation light (122) interacts with the optical excitation filter element (130), the dichroic filter (132) and the aperture stop (174) of the selected filter cell unit (128) and that the light (123) emitted from the sample (112) interacts with the dichroic filter (132), the aperture stop (174) and the optical detection filter element (134) of the selected filter cell unit (128).

Description

[0001] Automated PCR analyzer

[0002] Technical Field

[0003] The present invention relates to an automated polymerase chain reaction (PCR) analyzer and to a method of automated PCR analysis. The present invention further relates to a computer program and a computer-readable storage medium for performing the method. The devices and the method may specifically be used in the field of in-vitro diagnostics for analyzing sample, e.g. for determining a presence of at least one pathogen in the sample. However, other fields of application are also feasible.

[0004] Background art

[0005] In the field of in-vitro diagnostics, automated analyzers are generally widely used to perform analysis of samples without user interaction. Specifically, analyzers are known which perform polymerase chain reaction (PCR) processes fully automatically. For example, WO 97 / 46707 Al discloses a thermal cycling method and device. The device comprises a sample chamber whose temperature can be rapidly and accurately modulated over a range of temperatures needed to carry out a number of biological procedures, such as the DNA polymerase chain reaction. Biological samples are placed in glass micro capillary tubes and then located inside the sample chamber. A programmable controller regulates the temperature of the sample inside the sample chamber. Monitoring of the DNA amplification is monitored by fluorescence once per cycle or many times per cycle.

[0006] US 11,307,211 B2 describes a PCR tube that can reliably perform management of a sample, and an RFID sample management system and an RFID sample management method using the PCR tube. The PCR tube includes a tube body that has an opening at one end and has a collar part around the opening, and a lid part that is attachably and detachably mounted on the tube body and seals the opening of the tube body at the time of the mounting. An RFID tag having a passive antenna built therein is provided at the collar part or the lid part, and the antenna has directivity in a direction opposite to a bottom face of the tube body.

[0007] US 11,369,965 B2 discloses a PCR amplification and product detection system and method. The system utilizes a uniform and direct photonic heating subsystem to mediate reaction-by- reaction, high-throughput PCR amplification detectable by a fluorescence detection subsystem. Reaction-by-reaction temperature monitoring is used for dynamic feedback heat regulation.

[0008] US 10,222,598 B2 discloses an inverted microscope including: an epifluorescence illumination optical system configured to irradiate a specimen on a stage with epi-illumination light from below the stage; a transmitting illumination optical system configured to irradiate the specimen on the stage with transmitting illumination light from above the stage; an objective lens arranged below the stage and configured to collect the epi-illumination light on the specimen; and a light blocking unit configured to be arranged between the stage and the transmitting illumination optical system so as to be located on or deviated from an observation optical axis of the inverted microscope, and configured to be located at a light blocking position separated from the stage so as to block all direct light entering the objective lens at an angle not larger than an aperture angle of the objective lens.

[0009] US 10,274,713 B2 discloses a microscope including a stage on which a specimen is configured to be placed, an epi-illumination optical system having a fluorescence illumination light source configured to irradiate the specimen with excitation light of a predetermined wavelength, a transmitted-light illumination optical system, and a light shielding member. The transmitted-light illumination optical system includes a transmitted-light illumination light source having a white LED, and a condenser having a condenser lens configured to collect light emitted from the transmitted-light illumination light source onto the specimen and configured to move in a direction orthogonal to an illumination optical path so as to be insertable onto and removable from the illumination optical path. The light shielding member is configured to move in the direction orthogonal to the illumination optical path along with the condenser lens to block incidence of the excitation light from the epi-illumination optical system to the transmitted-light illumination optical system. EP 2 551 713 Al discloses a method involving analyzing a sample alternately or simultaneously in transmitted light bright field illumination and in incident light fluorescence illumination, and using a white light light-emitting diode as a light source for the transmitted light bright field illumination. A correction filter is activated both in transmitted light bright field illumination and in incident light fluorescence illumination at a location in an illumination beam path of the transmitted light bright field illumination. A spectral transmission profile of the correction filter is turned to the white light light-emitting diode.

[0010] DE 10 2007 022 666 Al discloses an optical illumination system for use in a microscope or electronic endoscope, including a solid-state illumination element that generates light having a spectral profile with peak intensities at a plurality of wavelengths such that the light emitted by the solid-state illumination element is perceived by an observer as white light, and a wavelength distribution converter element with a spectral transmittance profile containing specified wavelength ranges within which the transmittance is almost constant with increasing wavelength, such that a step of almost uniform intensity is formed, and having specified wavelength ranges within which the transmittance changes with increasing wavelength to form a transition region. Due to the combined effect of the solid-state lighting element and wavelength distribution converter element, the wavelength distribution of the light generated by the optical lighting system comes closer to the wavelength distribution of daylight than light generated by the solid-state lighting element alone.

[0011] US 8,097,865 B2 discloses an illumination device includes at least four semiconductor radiation sources for emitting optical radiation in respectively different emission wavelength ranges. At least one color splitter, which is reflective for optical radiation of the respective semiconductor radiation source, is assigned to each of at least three of the semiconductor radiation sources. The semiconductor radiation sources and the color splitters are arranged such that the optical radiation, which is emitted in each case from each of the semiconductor radiation sources, is coupled into a common illumination beam path section. In each case, one collimating unit, which collimates the optical radiation emitted by the respective semiconductor radiation source, is arranged in the beam path sections from the semiconductor radiation sources to the color splitters.

[0012] US 2023 / 125059 Al describes a fluorescence detection system, including apparatus and methods, suitable for qPCR and other fluorescence-based analyses. The system may comprise various components, including a stage, an illumination module, a detection module, and an optical relay structure. The stage may be configured to support a sample holder. The illumination module may include one or more discrete light sources configured to produce excitation light. The detection module may be configured to detect fluorescence emission light produced, in response to the excitation light, by a fluorescent sample positioned in the sample holder. The optical relay structure may include a beamsplitter assembly configured to direct the excitation light from the illumination module along an illumination path to the sample holder and to direct the fluorescence emission light from the sample holder along a response path to the imaging module. The system may enhance the quality of excitation light hitting samples in the sample holder.

[0013] WO 2005 / 068976 A2 describes a fluorometry device and method adapted to determine concentration of spectrally distinguishable species in a biological sample with a plurality of movable optical devices.

[0014] US 2005 / 151972 Al describes a fluorometry device and method adapted to determine concentration of spectrally distinguishable species in a biological sample with a plurality of movable optical devices.

[0015] Despite the advantages achieved by known methods and devices, several technical challenges remain. Specifically, known photometers in automated analyzers may use different measurement channels in different wavelength ranges. Each measuring channel usually has a different and possibly ill-defined optical path, and may require separate light sources and separate detectors. Further, a device-to-device variation of the performance of photometers may generally be very high due to the complexity of the concept and the disregard of fundamental optical design rules.

[0016] Problem to be solved

[0017] It is therefore desirable to provide methods and devices which at least partially address above-mentioned technical challenges. Specifically, an automated PCR analyzer and a method of automated PCR analysis shall be proposed which reduce the complexity and provide well-defined optical paths for different measuring channels. Summary

[0018] This problem is addressed by an automated polymerase chain reaction (PCR) analyzer, a method of automated PCR analysis, and a computer program and a computer-readable storage medium for performing the method, with the features of the independent claims. Advantageous embodiments which might be realized in an isolated fashion or in any arbitrary combinations are listed in the dependent claims as well as throughout the specification.

[0019] As used in the following, the terms “have”, “comprise” or “include” or any arbitrary grammatical variations thereof are used in a non-exclusive way. Thus, these terms may both refer to a situation in which, besides the feature introduced by these terms, no further features are present in the entity described in this context and to a situation in which one or more further features are present. As an example, the expressions “A has B”, “A comprises B” and “A includes B” may both refer to a situation in which, besides B, no other element is present in A (i.e. a situation in which A solely and exclusively consists of B) and to a situation in which, besides B, one or more further elements are present in entity A, such as element C, elements C and D or even further elements.

[0020] Further, it shall be noted that the terms “at least one”, “one or more” or similar expressions indicating that a feature or element may be present once or more than once typically will be used only once when introducing the respective feature or element. In the following, in most cases, when referring to the respective feature or element, the expressions “at least one” or “one or more” will not be repeated, non-withstanding the fact that the respective feature or element may be present once or more than once.

[0021] Further, as used in the following, the terms "preferably", "more preferably", "particularly", "more particularly", "specifically", "more specifically" or similar terms are used in conjunction with optional features, without restricting alternative possibilities. Thus, features introduced by these terms are optional features and are not intended to restrict the scope of the claims in any way. The invention may, as the skilled person will recognize, be performed by using alternative features. Similarly, features introduced by "in an embodiment of the invention" or similar expressions are intended to be optional features, without any restriction regarding alternative embodiments of the invention, without any restrictions regarding the scope of the invention and without any restriction regarding the possibility of combining the features introduced in such way with other optional or non-optional features of the invention. In a first aspect of the present invention, an automated polymerase chain reaction (PCR) analyzer for analyzing at least one sample is disclosed.

[0022] The term “automated” or “automatically” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a feature of a process of being performed completely by means of at least one device and / or computer and / or computer network, in particular without manual action and / or interaction with a user.

[0023] The term “analyzer” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a device configured for analyzing one or more samples. Specifically, the analyzer may be configured for analyzing one or more biological samples, such as samples comprising a bodily fluid, such as blood, plasma, serum, urine, saliva, interstitial fluid, or other types of body fluids. The analyzer may be configured for quantitatively and / or qualitatively analyzing the one or more sample, such as for determining a presence and / or a concentration of at least one analyte in the sample. The analyte may specifically comprise at least one pathogen in the sample of bodily fluid or any part thereof, such as a specific DNA fragment of the pathogen. The analyzer may be or may comprise a clinical diagnostic analyzer. For possible embodiments of the analyzer, reference may be made to commercially available analyzers, such as analyzers of the Roche cobas systems, e.g. the cobas® liat System. Other embodiments are also feasible.

[0024] Consequently, the term “analyzing”, as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a quantitative and / or qualitative determination of at least one analyte in the sample. The result of the analysis, as an example, may be a concentration of the analyte and / or the presence or absence of the analyte to be determined.

[0025] The term “polymerase chain reaction” or “PCR” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process of determining DNA fragments. Specifically, the PCR process may comprise performing consecutive amplification cycles such that DNA fragments present in the sample are amplified. For details on the PCR process, as an example, reference may be made to US 6,814,934 Bl.

[0026] The PCR analyzer may be or may comprise at least one instrument based on the polymerase chain reaction (PCR) process. The automated PCR analyzer may specifically be configured for automatically performing at least one PCR process for determining a presence of at least one pathogen in the sample. For example, the automated PCR analyzer may be configured for determining a presence of at least one pathogen in the sample selected from the group consisting of hepatitis B virus (HBV); hepatitis C virus (HCV); human immunodeficiency viruses (HIV), in particular HIV-1 and / or HIV-2; West Nile virus (WNV); hepatovirus A (HAV); parvovirus B19 (parvo B 19); hepatitis E virus (HEV); Chikungunya virus (CHIKV); dengue virus (DENV); Babesia; Zika virus; Usutu virus; Herpes simplex virus 1 (HSV-1) and (HSV-2); monkeypox (mpox); hepatitis delta virus (HDV); human papillomavirus (HPV); Chlamydia trachomatis (CT); Neisseria gonorrhoeae (NG); Trichomonas vaginalis (TV); Mycoplasma genitalium (MG); Piling inverting protein gene Neisseria gonorrhoeae (Piv NG); Cytomegalovirus (CMV); Epstein-Barr virus (EBV); BK polyomavirus (BKV); Mycobacterium tuberculosis (MTB); M. avium complex (MAC); M. avium-intra- cellulare (MAI); SARS-CoV-2; Influenza A; Influenza B; respiratory syncytial virus (RSV); C. difficile; Norovirus; Adenovirus (ADV); human Metapneumovirus (hMPV); Enterovirus- Rhinovirus (EV-RV); human parainfluenza viruses 1 - 4 (HPIV); Methicillin-resistent Staphylococcus aureus (MRSA); Staphylococcus aureus (SA); human leukocyte antigen B27 (HLA-B27); Group A Strep. However, other examples of pathogens are also feasible.

[0027] The automated PCR analyzer, as an example, may be a benchtop PCR analyzer. However, other examples, such as stand-alone PCR analyzer may also be feasible.

[0028] The term “sample” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to one or more biological samples. Specifically, the sample may comprise at least one aliquot or aliquant of a bodily fluid. The sample may comprise one or more of a sample of body fluid, a sample from a tissue or an organ, or a sample of wash / rinse fluid or a swab or smear obtained from an outer or inner body surface. The sample may be suspected to comprise an analyte. The sample may comprise a fluid sample obtained from, for example, a bodily fluid such as blood, plasma, serum, urine, saliva, interstitial fluid, or other types of body fluids. The sample may be obtained by use of brushes, (cotton) swabs, spatula, rinse / wash fluids, punch biopsy devices, puncture of cavities with needles or lancets, or by surgical instrumentation. The sample may be obtainable by dissolving, suspending or dispersing a sample of bodily fluid in an appropriate liquid such as water, optionally comprising one or more reactants.

[0029] The automated PCR analyzer comprises: at least one controller; at least one thermocycling apparatus configured for subjecting the sample to at least one temperature modulation controlled by the controller; and at least one photometer configured for detecting at least one optically detectable property of the sample, the photometer comprising at least one excitation light source configured for illuminating the sample with excitation light, the photometer further comprising at least one photodetector unit configured for detecting light emitted from the sample, the photometer further comprising a movable filter cell controllable by the controller, the movable filter cell comprising a plurality of filter cell units, each filter cell unit comprising at least one optical excitation filter element, at least one dichroic filter, at least one optical detection filter element and at least one aperture stop, wherein the photometer comprises a working position for the filter cell units, wherein the movable filter cell is configured for selectively positioning a selected filter cell unit selected from the plurality of filter cell units in the working position, wherein, in the working position, the selected filter cell unit is positioned such that the excitation light interacts with the optical excitation filter element, the dichroic filter and the aperture stop of the selected filter cell unit and that the light emitted from the sample interacts with the dichroic filter, the aperture stop and the optical detection filter element of the selected filter cell unit.

[0030] The term “controller” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary logic circuitry configured for performing basic operations of a computer or system, and / or, generally, to a device which is configured for performing calculations or logic operations. The controller may specifically be a computing unit comprising one or more processors, one or more memory devices and programmable input and / or output peripherals. The controller may be configured for processing basic instructions that drive a computer or system, e.g. at least one of the thermocycling apparatus, the photometer and the movable filter cell as will be outlined in further detail below. Specifically, the controller may comprise at least one device configured for operating the automated PCR analyzer, specifically at least one of the thermocycling apparatus, the photometer and the movable filter cell. The controller may comprise at least one arithmetic logic unit (ALU), at least one floating-point unit (FPU), such as a math co-processor or a numeric co-processor, a plurality of registers, specifically registers configured for supplying operands to the ALU and storing results of operations, and a memory, such as an LI and L2 cache memory. In particular, the controller may comprise a multi-core processor. Specifically, the controller may comprise a central processing unit (CPU). Additionally or alternatively, the controller’s elements may be contained in one single integrated circuitry (IC) chip. Additionally or alternatively, the controller may be or may comprise one or more application-specific integrated circuits (ASICs) and / or one or more field-programmable gate arrays (FPGAs) and / or one or more tensor processing unit (TPU) or the like. The controller specifically may be configured, such as by software programming, for performing one or more controlling and / or evaluation operations.

[0031] The controller, as an example, may be or may comprise at least one microcontroller. The devices of the microcontroller may be integrated on a single integrated circuit. Thus, specifically, the microcontroller may be an integrated component. The microcontroller may comprise a microprocessor configured for controlling and reading hardware sensors and, specifically, may be used as a building block for control operations.

[0032] The term “to control”, or any grammatical variation thereof, as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process of at least one of monitoring and regulating one or more operating parameter of another device. Specifically, the controller may be configured for monitoring and regulating one or more operating parameter of at least one of the thermocycling apparatus and the movable filter cell. For example, the controller may be configured for monitoring and regulating a heating power of the thermocycling apparatus. Additionally or alternatively, the controller may be configured for monitoring and regulating a position of the movable filter cell.

[0033] The term “thermocycling apparatus” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a device configured for applying at least one heat flux to one or more other devices or elements. The thermocycling apparatus may be configured for applying at least one heat flux to the sample received in the automated PCR analyzer, specifically to the sample received in a process chamber of the automated PCR analyzer. The thermocycling apparatus may specifically be configured for at least one of heating and cooling the sample. Thus, in particular, the thermocycling apparatus may be configured for being used as a heat source and a heat sink, specifically depending on an operational parameter of the thermocycling apparatus, e.g. depending on an electric current, such as an amount and / or a direction of the electric current, applied to the thermocycling apparatus. For example, the thermocycling apparatus may comprise at least one Peltier element. Other examples are, however, also feasible, such as a combination of two different device, one being used as a heat source and the other being used as a heat sink.

[0034] The term “subjecting” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process of controllably varying one or more properties of a material, device or system. Specifically, the subjecting of the sample to the at least one temperature modulation may comprise controllably varying the temperature of the sample.

[0035] The term “temperature modulation” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a sequence of temperature steps. Specifically, the temperature modulation may comprise a plurality of temperature steps, such as at least two temperature steps, being performed consecutively, such as in a given or predefined order. The temperature steps may comprise different temperatures. Thus, specifically, the temperature steps may comprise changing the temperature to a target temperature and maintaining the target temperature for a given or predefined period of time. The sequence of temperature steps may specifically comprise a repeating order of temperature steps, which may specifically referred herein to as “amplification cycles”. The temperature modulation may comprise a predetermined number of amplification cycles. Each amplification cycles may comprise at least one denaturation temperature and at least one annealing temperatures. Optionally, the amplification cycle may further comprise at least one elongation temperature.

[0036] As outlined above, the automated PCR analyzer comprises the at least one photometer configured for detecting the at least one optically detectable property of the sample. The term “photometer” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to at least one device or combination of devices configured for quantitatively or qualitatively determining at least one item of optical information on an object. Specifically, photometer may be configured for determining the item of optical information on the object as a function of a wavelength, such as for two or more different wavelengths. The photometer may comprise a plurality of measurement channels, wherein each measurement may be associated with a specific wavelength range. The photometer may further be configured for determining the item of optical information in each of the measurement channel, i.e. for each of the specific wavelength ranges.

[0037] The photometer may specifically be or may comprise an optical system, i.e. an arrangement of optical components configured for guiding the excitation light from the excitation light source to the sample, thereby defining an excitation optical path, and, optionally a fraction of the excitation light to a reference photodetector. The optical system may further be configured for guiding the light emitted from the sample, such as light generated by photoluminescence of the sample, from the sample to the photodetector unit, thereby defining an emission optical path. In the photometer, an optical path, specifically the excitation optical path and the emission optical path, may be describe the propagation of light in the optical system. The optical system, specifically each of the excitation optical and the emission optical path, may consist of a variety of active components, such as light sources and detectors, and passive components, such as lenses, mirrors, filters, gratings and apertures.

[0038] The term “detecting” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process of at least one of determining, measuring and monitoring at least one parameter, qualitatively and / or quantitatively, such as at least one of a physical parameter, a chemical parameter and a biological parameter. Specifically, the detecting may comprise quantitatively or qualitatively determining at least one item of optical information on the sample.

[0039] The term “optically detectable property” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to at least one item of optical information. The optically detectable property of the sample may specifically comprise at least one item of optical information indicating an intensity of light reflected and / or emitted by the sample. For example, the optically detectable property may comprise at least one item of optical information characterizing at least one of an absorption, a reflection and an emission of the sample, either by itself or after illumination with external light. The optically detectable property of the sample may comprise at least one optical property indicating a wavelength-shifted emission of the excitation light at the sample. The optically detectable property of the sample may comprise at least one item of optical information indicating one or more scattering properties of the sample. The optically detectable property of the sample may specifically comprise at least one photoluminescence property of the sample, by way of example at least one of a fluorescence property of the sample, a phosphorescence property of the sample, or any scattering or other property leading to a spectral shift in the photoluminescence against the excitation light.

[0040] The term “excitation light source” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary device configured for generating light. As used herein, the term “light” is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to electromagnetic radiation in one or more of the infrared, the visible and the ultraviolet spectral range. Herein, the term “ultraviolet spectral range”, generally, refers to electromagnetic radiation having a wavelength of 1 nm to 380 nm, preferably of 100 nm to 380 nm. Further, in partial accordance with standard ISO-21348 in a valid version at the date of this document, the term “visible spectral range”, generally, refers to a spectral range of 380 nm to 760 nm. The term “infrared 40 spectral range” (IR) generally refers to electromagnetic radiation of 760 nm to 1000 pm, wherein the range of 760 nm to 1.5 pm is usually denominated as “near infrared spectral range” (NIR) while the range from 1.5 pm to 15 pm is denoted as “mid infrared spectral range” (MidlR) and the range from 15 pm to 1000 pm as “far infrared spectral range” (FIR).

[0041] The excitation light source may be or may comprise at least one electrical light source, such as an electrically driven light source. For example, the excitation light source may comprise at least one light-emitting diode (LED), specifically a broadband LED, more specifically a light conversion LED, more specifically a white LED. The excitation light source may comprise a singled LED. Alternatively, the excitation light source may comprise a plurality of LEDs. The excitation light source may comprise the plurality of LEDs arranged in an array, specifically in an m x n matrix, more specifically in a 2 x 2 matrix. The plurality of LEDs may comprise white LEDs or colored LEDs, specifically colored LEDs of different wavelengths.

[0042] The term “illuminating” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process of exposing at least one element to light. The term “excitation light” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to light configured for exciting the sample. Generally, the excitation light may comprise light propagating from the excitation light source to the sample, before and after passing the selected filter cell unit, specifically before and after being optically filtered by the excitation filter and the dichroic filter. The excitation light may be configured for interacting with the sample such that the sample emits photoluminescence light. Specifically, the excitation light may be configured for being absorbed by the sample causing the sample to emit photoluminescence light.

[0043] The term “light emitted from the sample” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to light being at least one of reflected and / or emitted by the sample upon illumination by excitation light. Generally, the light emitted from the sample may comprise light propagating from the sample to the photodetector unit, before and after passing the selected filter cell unit, specifically before and after being filtered by the dichroic filter and the detection filter element. The light emitted from the sample may comprise light emitted and / or reflected by the sample, in reaction to the illumination with the excitation light, e.g. photoluminescence light emitted by the sample after optical excitation of the sample by the excitation light. Thus, the light emitted from the sample may directly or indirectly be generated through the illumination of the sample with excitation light. As used herein, “photoluminescence light”, may refer, without limitation, to any physical mechanisms of a material or object of generating photons in response to excitation light. The photoluminescence light may comprise wavelength-shifted light emitted by the sample due to excitation of at least one mechanism in the sample by the excitation light. For example, photoluminescence light may comprise light generated by the sample due to fluorescence, phosphorescence or any other property leading to a spectral shift in the photoluminescence against the excitation light.

[0044] The term “photodetector unit” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a device or combination of devices configured for detecting light. The photodetector unit may comprise at least one photosensitive element which is configured for generating at least one detector signal upon illumination by light. Specifically, the photodetector unit may be configured for generating at least one detector signal indicating an amount of light impinging on a photosensitive area of the photosensitive element. The photodetector unit may comprise at least one light-sensitive element or layer which is configured for detecting incident light, e.g. the light emitted by the sample. The photodetector unit may comprise at least one device configured for photodetection, specifically at least one device comprising at least one material or a combination of materials configured for photodetection. As an example, the photodetector unit may comprise at least one of a semiconductor photodetector, specifically one or more of a silicon photoconductor, a germanium photoconductor, a gallium arsenide photoconductor or the like, a photodiode, a phototransistor, a CCD sensor, a CMOS sensor and a photomultiplier.

[0045] The term “movable filter cell” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a set of two or more filter cell units forming a whole. The two or more filter cell units may specifically be coupled to each other such that the plurality of filer cells can be handled as a single unit. The two or more filter cell units of the movable filter cell may be automatically interchangeably, such as without user interaction. Specifically, the movable filter cell may comprise two or more filter cell units which can be positioned in and out of an optical path of the excitation light and the light emitted from the sample without user interaction. The movable filter cell may be configured such that only one of the filter cell units is in the optical path of the excitation light and the light emitted from the sample at a time. The movable filter cell may comprise the two or more filter cell units, each of the filter cell units being associated with at least one measurement channel of the photometer. The movable filter cell may be controllable by the controller.

[0046] The movable filter cell may specifically comprise at least two filter cell units, specifically at least four filter cell units, more specifically at least six filter cell units. The optical excitation filter element and the optical detection filter element of each filter cell unit may be configured for filtering light in a specific wavelength range. The specific wavelength range may be different for each filter cell unit. The different wavelength ranges may define the measurement channels of the photometer.

[0047] The movable filter cell may comprise at least one of a linear stage and a filter wheel carrying the plurality of filter cell units. For example, the movable filter cell may comprise at least one linear stage. The linear stage may comprise at least two side parts having the plurality of filter cell units arranged in between the two side parts. The linear stage may further comprise plain bearings directly integrated into the at least two side parts. The photometer may further comprise at least one guide rod at least partially received in the plain bearings of the linear stage for guiding movement of the movable filter cell. The photometer may further comprise at least one linear actuator, specifically at least one toothed belt drive, for moving the movable filter cell. Alternatively or additionally, the movable filter cell may comprise at least one filter wheel carrying the plurality of filter cell units. The photometer may specifically comprise at least one actuator for turning the filter wheel to move the filter cell unit into and out of the optical path of the excitation light and the light emitted from the sample.

[0048] The term “filter cell unit” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an optical assembly of at least one optical excitation filter element, at least one dichroic filter, at least one optical detection filter element and at least one aperture stop. Optionally, the filter cell unit may further comprise at least one optical reference filter element, as will be outlined in further detail below. The optical assembly of the optical excitation element, the dichroic filter, the optical detection filter element, the aperture stop, and optionally the optical reference filter element, may form a single unit or, alternatively, may comprise at least two separate components which may be handled independently and may be connectable.

[0049] For example, each filter cell unit may comprise the optical excitation filter element, the dichroic filter, the optical detection filter element and the aperture stop in a single filter cell unit. Thus, in this example, the filter cell unit may be handled as a single unit. Alternatively, each filter cell unit may comprise at least one first submodule and at least one second submodule. The first submodule may comprise the optical excitation filter element. The second submodule may comprise the optical detection filter element. At least one of the first submodule and the second submodule may comprise the dichroic filter and the aperture stop. For example, the first submodule may comprise the optical excitation filter element the dichroic filter and the aperture stop, wherein the second submodule may comprise the optical detection filter element. Alternatively, the dichroic filter and the aperture stop may also be part of the second submodule. The first and the second submodule are movable independent from each other. The first and the second submodule may be connectable such as to provide a common optical path for the excitation light and the light emitted from the sample. The first and second submodule being movable independent from each other may allow multiplexing of channels, i.e. combining a selected optical path defined by the optical excitation filter element, the dichroic filter and the aperture stop with a selected optical path defined by the optical detection filter element. The multiplexing of channels may increase flexibility of the photometer with regard to the measurement channels. The term “movable” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a property of an element or device of being capable to change position. The filter cell units of the movable filter cell may be configured for changing position. Specifically, the filter cell units of the movable filter cell may be movable such that the filter cell units can be positioned in and out of an optical path. The filter cell units may be movable to position one filter cell unit in an optical path of the excitation light and the light emitted from the sample.

[0050] The term “filter element” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an optical element configured having wavelength- selective properties. Specifically, the filter element may be configured for selectively transmitting light with at least one wavelength range. The filter element may comprise at least one of a broadband filter element, a shortpass filter element and a longpass filter element.

[0051] The term “optical excitation filter element” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a filter element configured for selecting wavelengths of the excitation light. Similarly, the term “optical detection filter element” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a filter element configured for selecting wavelengths of the light emitted from the sample. As an example, each of the optical excitation filter element and the optical detection filter element may comprise at least one optical element having wavelength-selecting properties, such as at least one optical filter, e.g. at least one optical interference filter and / or at least one optical absorption filter.

[0052] The term “dichroic filter” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an optical element configured for reflecting light within at least one wavelength range and for transmitting light within at least one other wavelength range. The dichroic filter may comprise at least one optical element having wavelength-dependent reflecting, refracting and transmitting properties. For example, the dichroic filter may comprise a multiple layer setup of dielectric materials having different refractive indices. The wavelength-dependent reflecting, refracting and transmitting properties may rely on the principle of interference at the interfaces of the multiple layers.

[0053] Further, as outlined above, each filter cell unit comprises the at least one aperture stop. The term “aperture stop” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an optical element having at least one hole or opening for transmitting light there through. Specifically, light irradiating the aperture stop may only be transmitted through the at least one hole or opening of the aperture stop. Thus, the aperture stop may comprise at least one non-transparent material. The opening or hole of the aperture stop may have a regular shape, such as a circular or a rectangular shape, or an irregular shape, such as a polygonal shape. The aperture stop may be at least one elliptically shaped aperture stop. The aperture stop may specifically be a separate optical element providing a hole or an opening for the transmission of light. Additionally or alternatively, the aperture stop may also be at least partially integrated into one or more of the other elements of the photometer, specifically of the filter unit cells. For example, at least one of the optical excitation filter element, the dichroic filter and the optical detection filter element may comprise a filter element being surrounded by at least one optically non-transparent material. Thus, in this example, the aperture may be at least partially integrated into one or more of the optical excitation filter element, the dichroic filter and the optical detection filter element. The aperture stop may be configured for controlling an amount of light present in the photometer, specifically by limiting light rays, such as light rays of the excitation light and / or light rays of the light emitted from the sample, being transmitted through the aperture stop. Specifically, by using the aperture stop, it may be possible to control an amount of light being present in the optical system of the photometer. The aperture stop may be arranged in the beam path of at least one of the excitation light and the light emitted from the sample, specifically on top of the dichroic filter.

[0054] The movable filter cell may further comprise at least one actuator for moving the filter cell units into the working position and out of the working position.

[0055] The term “working position” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a position of the movable filter cell establishing at least one of an excitation optical path and an emission optical path. The working position may be a position of the movable filter cell enabling illumination of the sample with the excitation light and detection of the light emitted from the sample by the photodetector unit. The working position may be a position of the movable filter cell in which the light emitted from the sample propagates through the selected filter cell unit to the sample and the light emitted from the sample propagates through the selected filter cell unit to the photodetector unit. Thus, in particular, the working position may comprise an appropriate mechanical position for the filter cell unit in an optical system of the photometer. As outlined above, an actuator may be configured for moving the filter cell units of the movable filter cell in and out of the optical path of the excitation light and the light emitted from the sample.

[0056] The term “selectively positioning” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process of specifically placing or arranging the plurality of filter cell units. The selective positioning may comprise selecting one filter cell unit from the plurality of filer cells and changing the position of the movable filter cell such that the selected filter cell unit is in the working position. The controller may be configured for controlling the movable filter cell to selectively position the selected filter cell unit into the working position.

[0057] The term “selected filter cell unit” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a filter cell unit which is to be positioned in the working position. The selected filter cell unit may comprise a filter cell unit of the plurality of filter cell units associated with a measurement channel for which the detection of the optically detectable property is to be performed. In the working position, the selected filter cell unit may be positioned such that the excitation light may pass to the sample, specifically after passing the optical excitation filter element. In the working position, the selected filter cell unit may be positioned such that the light emitted from the sample may pass to the photodetector unit, specifically after passing the optical detection filter element.

[0058] In the working position, the selected filter cell unit may be positioned such that the excitation light as emitted by the excitation light source illuminates the excitation filter. The excitation light may interact with the optical excitation filter element such that light within an illumination wavelength range passes the optical excitation filter element. Further, the excitation light, specifically the excitation light as filtered by the optical excitation filter element, may interact with the dichroic filter such that light within the illumination wavelength range is reflected or transmitted onto the sample. For example, in the working position, the excitation light may comprise light within the illumination wavelength range being reflected by the dichroic mirror to the sample. The light emitted from the sample may be transmitted by the dichroic mirror to the optical detection filter element and the photodetector unit. Alternatively, in the working position, the excitation light may comprise light within the illumination wavelength range being transmitted by the dichroic mirror to the sample. In this case, the light emitted from the sample may be reflected by the dichroic mirror to the optical detection filter element and the photodetector unit.

[0059] In the working position, the selected filter cell unit may be positioned such that the light emitted from the sample as emitted by the sample illuminates the dichroic filter. The light emitted from the sample may interact with the dichroic filter and the optical detection filter element such that light within a detection wavelength range passes the dichroic filter and the optical detection filter element. The light emitted from the sample, after passing the dichroic filter and the optical detection filter element, may illuminate the photodetector unit.

[0060] The automated PCR analyzer may further comprise at least one reference element. The photometer may be configured for illuminating the reference element with reference excitation light from the excitation light source. The photometer may be further configured for detecting the reference excitation light on the reference element. The reference excitation light may comprise part of the excitation light after passing the optical excitation filter element and the dichroic filter of the selected filter cell unit. As an example, the reference element may comprise at least one reference photodetector. The reference photodetector may comprise at least one device configured for photodetection, specifically at least one device comprising at least one material or a combination of materials configured for photodetection. As an example, the reference photodetector may comprise at least one of a semiconductor photodetector, specifically one or more of a silicon photoconductor a germanium photoconductor, a gallium arsenide photoconductor or the like, a photodiode, a phototransistor, a CCD sensor, a CMOS sensor, and a photomultiplier. Each filter cell unit may further comprise at least one optical reference filter element. In the working position, the selected filter cell unit may be positioned such that the reference excitation light interacts with the optical reference filter element. Specifically, in the working position, the selected filter cell unit may be positioned such that the reference excitation light illuminates the optical reference filter element and the reference excitation light as transmitted by the optical reference filter element illuminates the reference photodetector. The reference element may further comprise at least one reference lens. The photometer may be configured such that the reference excitation light passes the reference lens, specifically after passing the selected filter cell unit.

[0061] The photometer may further comprise at least one detector lens. The photometer may be configured such that the light emitted from the sample passes the detector lens, specifically after passing the selected filter cell unit. A presence of at least one detector lens may specifically be dependent on a size of the photodetector unit. Alternatively or additionally, the photometer may further comprise at least one excitation light source lens. The photometer may be configured such that the excitation light source passes the excitation light source lens onto the selected filter cell unit. Alternatively or additionally, the photometer may further comprise at least one object lens. The photometer may be configured such that the excitation light and the light emitted from the sample pass the object lens. The photometer may have an epifluorescence optical design. In the epifluorescence optical design, the excitation light and the light emitted from the sample may pass the same at least one object lens. A presence of the excitation light source lens and the detection lens may specifically be dependent on an illumination power provided by the excitation light source, e.g. such that enough illumination power is provided to the sample to cause photoluminescence at the sample. Thus, specifically, the photometer may also be embodied with lenses.

[0062] In a further aspect of the present invention, a method of automated PCR analysis is disclosed. The method comprises using the automated PCR analyzer according to the present invention, such as according to any one of the embodiments disclosed above and / or according to any one of the embodiments described in further detail below.

[0063] The method comprises the following steps that may be performed in the given order. However, a different order may also be possible. In particular, one, more than one or even all of the method steps may be performed once or repeatedly. Further, the method steps may be performed successively or, alternatively, one or more of the method steps may be performed in a timely overlapping fashion or even in a parallel fashion and / or in a combined fashion. The method may further comprise additional method steps that are not listed.

[0064] The method further comprises: i) subjecting at least one sample, by using the thermocycling apparatus, to at least one temperature modulation controlled by the controller; ii) moving a selected filter cell unit selected from the plurality of filter cell units in the working position; iii) illuminating, by using the excitation light source, the at least one sample via the selected filter cell unit; and iv) detecting, by using the photometer, at least one optically detectable property of the sample.

[0065] The method may specifically comprise repeating steps i) to iv) for a predetermined number of amplification cycles. For example, the method may comprise repeating steps i) to iv) for a predetermined number of 1 to 50 amplification cycles.

[0066] The method may specifically be computer-controlled, such as by hardware and / or software programming of the controller.

[0067] In a further aspect of the present invention, a computer program is disclosed, comprising instructions which, when the program is executed by the automated PCR analyzer according to the present invention, such as according to any one of the embodiments disclosed above and / or according to any one of the embodiments described in further detail below, cause the automated PCR analyzer to perform the method according to the present invention, such as according to any one of the embodiments disclosed above and / or according to any one of the embodiments described in further detail below.

[0068] In a further aspect of the present invention, a computer-readable storage medium, specifically a non-transient computer-readable medium, is disclosed, comprising instructions which, when the instructions are executed by the automated PCR analyzer according to the present invention, such as according to any one of the embodiments disclosed above and / or according to any one of the embodiments described in further detail below, cause the automated PCR analyzer to perform the method according to the present invention, such as according to any one of the embodiments disclosed above and / or according to any one of the embodiments described in further detail below.

[0069] As used herein, the term “computer-readable storage medium” specifically may refer to non- transitory data storage means, such as a hardware storage medium having stored thereon computer-executable instructions. The computer-readable storage medium specifically may be or may comprise a storage medium such as a random-access memory (RAM) and / or a read-only memory (ROM). The computer-readable storage medium may be or may comprise a computer-readable data carrier. In a further aspect of the present invention, a use of an automated PCR analyzer according to the present invention, such as according to any one of the embodiments disclosed above and / or according to any one of the embodiments described in further detail below, is disclosed. The automated PCR analyzer is used for performing at least one PCR process for determining a presence of at least one pathogen in the sample selected from the group consisting of hepatitis B virus (HBV); hepatitis C virus (HCV); human immunodeficiency viruses (HIV), in particular HIV-1 and / or HIV-2; West Nile virus (WNV); hepatovirus A (HAV); parvovirus B19 (parvo B 19); hepatitis E virus (HEV); Chikungunya virus (CHIKV); dengue virus (DENV); Babesia; Zika virus; Usutu virus; Herpes simplex virus 1 (HSV-1) and (HSV-2); monkeypox (mpox); hepatitis delta virus (HDV); human papillomavirus (HPV); Chlamydia trachomatis (CT); Neisseria gonorrhoeae (NG); Trichomonas vaginalis (TV); Mycoplasma genitalium (MG); Piling inverting protein gene Neisseria gonorrhoeae (Piv NG); Cytomegalovirus (CMV); Epstein-Barr virus (EBV); BK polyomavirus (BKV); Mycobacterium tuberculosis (MTB); M. avium complex (MAC); M. avium-intra- cellulare (MAI); SARS-CoV-2; Influenza A; Influenza B; respiratory syncytial virus (RSV); C. difficile; Norovirus; Adenovirus (ADV); human Metapneumovirus (hMPV); Enterovirus- Rhinovirus (EV-RV); human parainfluenza viruses 1 - 4 (HPIV); Methicillin-resistent Staphylococcus aureus (MRSA); Staphylococcus aureus (SA); human leukocyte antigen B27 (HLA-B27); Group A Strep.

[0070] Further disclosed and proposed herein is a computer program including computer-executable instructions for performing the method according to the present invention in one or more of the embodiments enclosed herein when the instructions are executed on a computer or computer network. Specifically, the computer program may be stored on a computer-readable data carrier and / or on a computer-readable storage medium.

[0071] Thus, specifically, one, more than one or even all of method steps a) to d) as indicated above may be performed by using a computer or a computer network, preferably by using a computer program.

[0072] Further disclosed and proposed herein is a computer program product having program code means, in order to perform the method according to the present invention in one or more of the embodiments enclosed herein when the program is executed on a computer or computer network. Specifically, the program code means may be stored on a computer-readable data carrier and / or on a computer-readable storage medium. Further disclosed and proposed herein is a data carrier having a data structure stored thereon, which, after loading into a computer or computer network, such as into a working memory or main memory of the computer or computer network, may execute the method according to one or more of the embodiments disclosed herein.

[0073] Further disclosed and proposed herein is a non-transient computer-readable medium including instructions that, when executed by one or more processors, cause the one or more processors to perform the method according to one or more of the embodiments disclosed herein.

[0074] Further disclosed and proposed herein is a computer program product with program code means stored on a machine-readable carrier, in order to perform the method according to one or more of the embodiments disclosed herein, when the program is executed on a computer or computer network. As used herein, a computer program product refers to the program as a tradable product. The product may generally exist in an arbitrary format, such as in a paper format, or on a computer-readable data carrier and / or on a computer-readable storage medium. Specifically, the computer program product may be distributed over a data network.

[0075] Finally, disclosed and proposed herein is a modulated data signal which contains instructions readable by a computer system or computer network, for performing the method according to one or more of the embodiments disclosed herein.

[0076] Referring to the computer-implemented aspects of the invention, one or more of the method steps or even all of the method steps of the method according to one or more of the embodiments disclosed herein may be performed by using a computer or computer network. Thus, generally, any of the method steps including provision and / or manipulation of data may be performed by using a computer or computer network. Generally, these method steps may include any of the method steps, typically except for method steps requiring manual work, such as providing the samples and / or certain aspects of performing the actual measurements.

[0077] Specifically, further disclosed herein are:

[0078] - a computer or computer network comprising at least one processor, wherein the processor is adapted to perform the method according to one of the embodiments described in this description,

[0079] - a computer loadable data structure that is adapted to perform the method according to one of the embodiments described in this description while the data structure is being executed on a computer, - a computer program, wherein the computer program is adapted to perform the method according to one of the embodiments described in this description while the program is being executed on a computer,

[0080] - a computer program comprising program means for performing the method according to one of the embodiments described in this description while the computer program is being executed on a computer or on a computer network,

[0081] - a computer program comprising program means according to the preceding embodiment, wherein the program means are stored on a storage medium readable to a computer,

[0082] - a storage medium, wherein a data structure is stored on the storage medium and wherein the data structure is adapted to perform the method according to one of the embodiments described in this description after having been loaded into a main and / or working storage of a computer or of a computer network, and

[0083] - a computer program product having program code means, wherein the program code means can be stored or are stored on a storage medium, for performing the method according to one of the embodiments described in this description, if the program code means are executed on a computer or on a computer network.

[0084] The devices and method according to the present invention may provide a large number of advantages over known methods and devices. Specifically, the automated PCR analyzer may provide one single, well-defined optical path for all the wavelength-channels. Further, the automated PCR analyzer may require only a single excitation light source, a single photodetector unit and a single reference detector for providing multiple wavelength channels. The photometer may additionally comprise at least one imaging system comprising one or more optical lenses. However, the imaging system may only be optional. Thus, in principle, the photometer with the movable filter cell may be designed in a small and compact fashion compared to a microscopic setup. The photometer may specifically be designed in a compact fashion to be incorporated in a benchtop automated PCR analyzer.

[0085] Specifically, the photometer may have a common optical path for all measurement channels enabled by using the movable filter cell with the plurality of moveable, dedicated filter cell units for each measurement channel. The photometer may require only a single excitation light source, such as a white LED source, and a common photodetector unit, such as a fluorescence detector, for all measurement channels. The automated PCR analyzer may specifically provide a clear optical design allowing for a very low device-to-device variation in photometer performance. The photometer may comprise at least one imaging system. The optical design of the photometer may be based on the principles of standard epifluorescence microscopy.

[0086] Further, the single common optical path of the excitation light and the light emitted from the sample for all measurement channels may be defined by the excitation light source, the selected filter cell unit in the working position and the photodetector unit. In the optical path, an optical imaging system may take the energy from the excitation light source to the sample, and optionally a fraction of the excitation light to the reference detector, and the light emitted from the sample, such as by emission via photoluminescence, of the sample to the photodetector unit. In case the photosensitive area of the photodetector unit is large enough to capture the incoming light emitted from the sample, no optical lenses may be required in front of the photodetector unit. Similarly, depending on a minimum optical power required at the sample and a total optical power of the excitation light source, the optical lenses in a beam path between the excitation light source and in front of the sample may not be required. In other words, in the simplest configuration, the setup of the photometer may work even without an imaging system around the movable filter cell. The reference detector may specifically be optional.

[0087] Alternatively or additionally, the optical imaging system may be integrated into the filter cell units of the movable filter cell. An actuator may be configured for moving the filter cell units in and out the optical path. For example, the filter cell units may be placed on a linear stage or a filter wheel. Each filter cell unit may comprise at least of a set of optical excitation filter element, detection filter element and one or more dichroic filters in order to excite and detect photoluminescence in a particular wavelength range or spectral range. The requirements for the imaging system for PCR analysis may be very much relaxed compared to a microscopic system.

[0088] As outlined above, the photometer may comprise at least one imaging system by combining the filter cell units with additional optical lenses. Additionally, the movable filter cell may comprise aperture stops defining an angular extent of an optical field conveyed from the excitation light source to the sample and to the photodetector unit. The aperture stop may be located on top of the dichroic filter.

[0089] The excitation light may specifically comprise a single or a matrix of white light LEDs (WLEDs) offering the wavelength range required in the PCR application. When a matrix of LEDs is used, e.g. a 2x2 matrix of LEDs, the combination of LEDs of different wavelengths may cover an even larger spectral range than a single WLED. The photodetector unit may specifically comprise semiconductor photodetectors or photomultiplier tubes. For example, the photodetector unit may comprise silicon photodetectors.

[0090] The opto-mechanical design of the photometer with the filter cell units, e.g. the linear movement of the filter cell units on a linear stage, may allow a very compact design and may therefore be particularly suitable for a benchtop PCR analyzer. However, other embodiments of the automated PCR analyzer in other applications or systems, such as in standalone laboratory systems, are also feasible. Specifically in these configurations, filter wheels may be used as an alternative to the linear stage.

[0091] The linear stage may be guided by plain bearings directly integrated in the two side parts of the linear stage. The large bearing distance may specifically be favorable for precision and may reduce the system's sensitivity with regard to blocking. This may be of particular importance with regard to the number of movements within the PCR process. Additionally, the linear stage may also provide advantages for assembly since the filter cell units may be held together tightly by the two side parts.

[0092] Each filter cell unit may form a single, movable unit. Additionally or alternatively, each filter cell unit may comprise at least one first submodule and at least one second submodule, which may specifically be movable independently from each other, such as by using a dedicated actuator for each of the submodules. Thus, in this configuration, the filter cell units may not comprise a fixed assembly of the optical excitation filter element, the dichroic filter and the optical detection filter element. The optical excitation filter element and the dichroic filter in the first submodule may be freely combined with any of the optical detection filter elements in the second submodule. This flexible configuration may allow multiplexing.

[0093] Summarizing and without excluding further possible embodiments, the following embodiments may be envisaged:

[0094] Embodiment 1 : An automated polymerase chain reaction (PCR) analyzer for analyzing at least one sample, comprising: at least one controller; at least one thermocycling apparatus configured for subjecting the sample to at least one temperature modulation controlled by the controller; and at least one photometer configured for detecting at least one optically detectable property of the sample, the photometer comprising at least one excitation light source configured for illuminating the sample with excitation light, the photometer further comprising at least one photodetector unit configured for detecting light emitted from the sample from the sample, the photometer further comprising a movable filter cell controllable by the controller, the movable filter cell comprising a plurality of filter cell units, each filter cell unit comprising at least one optical excitation filter element, at least one dichroic filter, at least one optical detection filter element and at least one the aperture stop, wherein the photometer comprises a working position for the filter cell units, wherein the movable filter cell is configured for selectively positioning a selected filter cell unit selected from the plurality of filter cell units in the working position, wherein, in the working position, the selected filter cell unit is positioned such that the excitation light interacts with the optical excitation filter element and the dichroic filter of the selected filter cell unit and that the light emitted from the sample interacts with the dichroic filter, the aperture stop and the optical detection filter element of the selected filter cell unit.

[0095] Embodiment 2: The automated PCR analyzer according to the preceding embodiment, wherein each filter cell unit comprises the optical excitation filter element, the dichroic filter, the optical detection filter element and the aperture stop in a single filter cell unit.

[0096] Embodiment 3 : The automated PCR analyzer according to any one of the preceding embodiments, wherein each filter cell unit comprises at least one first submodule and at least one second submodule, wherein the first submodule comprises the optical excitation filter element, wherein the second submodule comprises the optical detection filter element, wherein the first and the second submodule are movable independent from each other.

[0097] Embodiment 4: The automated PCR analyzer according the preceding embodiment, wherein at least one of the first submodule and the second submodule comprises the dichroic filter and the aperture stop.

[0098] Embodiment 5: The automated PCR analyzer according to any one of the preceding embodiments, wherein the aperture stop is arranged in the beam path of at least one the excitation light and the light emitted from the sample, specifically on top of the dichroic filter. Embodiment 6: The automated PCR analyzer according to any one of the preceding embodiments, wherein the movable filter cell comprises at least two filter cell units, specifically at least four filter cell units, more specifically at least six filter cell units, wherein the optical excitation filter element and the optical detection filter element of each filter cell unit are configured for filtering light in a specific wavelength range, wherein the specific wavelength range is different for each filter cell unit.

[0099] Embodiment 7: The automated PCR analyzer according to any one of the preceding embodiments, wherein the movable filter cell comprises at least one of a linear stage and a filter wheel carrying the plurality of filter cell units.

[0100] Embodiment 8: The automated PCR analyzer according to any one of the preceding embodiments, wherein the movable filter cell comprises at least one linear stage, wherein the linear stage comprises at least two side parts having the plurality of filter cell units arranged in between the two side parts, wherein the linear stage further comprises plain bearings directly integrated into the at least two side parts.

[0101] Embodiment 9: The automated PCR analyzer according to the preceding embodiment, wherein the photometer further comprises at least one guide rod at least partially received in the plain bearings of the linear stage for guiding movement of the movable filter cell.

[0102] Embodiment 10: The automated PCR analyzer according to the preceding embodiment, wherein the photometer further comprises at least one linear actuator, specifically at least one toothed belt drive, for moving the movable filter cell.

[0103] Embodiment 11 : The automated PCR analyzer according to any one of the preceding embodiments, wherein the movable filter cell further comprises at least one actuator for moving the filter cell units into the working position and out of the working position.

[0104] Embodiment 12: The automated PCR analyzer according to any one of the preceding embodiments, wherein the excitation light comprises light propagating from the excitation light source to the sample, before and after passing the selected filter cell unit, specifically before and after being optically filtered by the excitation filter and the dichroic filter. Embodiment 13: The automated PCR analyzer according to any one of the preceding embodiments, wherein each of the optical excitation filter element and the optical detection filter element comprises at least one optical element having wavelength-selecting properties, such as at least one optical filter.

[0105] Embodiment 14: The automated PCR analyzer according to any one of the preceding embodiments, wherein the light emitted from the sample comprises light propagating from the sample to the photodetector unit, before and after passing the selected filter cell unit, specifically before and after being filtered by the dichroic filter and the detection filter element.

[0106] Embodiment 15: The automated PCR analyzer according to any one of the preceding embodiments, wherein the dichroic filter comprises at least one optical element having wavelength-dependent reflecting, refracting and transmitting properties.

[0107] Embodiment 16: The automated PCR analyzer according to any one of the preceding embodiments, further comprising at least one reference element, wherein the photometer is configured for illuminating the reference element with reference excitation light from the excitation light source and wherein the photometer is further configured for detecting the reference excitation light on the reference element.

[0108] Embodiment 17: The automated PCR analyzer according to the preceding embodiment, wherein the reference element comprises at least one reference photodetector.

[0109] Embodiment 18: The automated PCR analyzer according to any one of the two preceding embodiments, wherein each filter cell unit further comprises at least one optical reference filter element, wherein, in the working position, the selected filter cell unit is positioned such that the reference excitation light interacts with the optical reference filter element.

[0110] Embodiment 19: The automated PCR analyzer according to any one of the three preceding embodiments, wherein the reference element further comprises at least one reference lens, wherein the photometer is configured such that the reference excitation light passes the reference lens, specifically after passing the selected filter cell unit. Embodiment 20: The automated PCR analyzer according to any one of the four preceding embodiments, wherein the reference excitation light comprises part of the excitation light after passing the optical excitation filter element and the dichroic filter of the selected filter cell unit.

[0111] Embodiment 21 : The automated PCR analyzer according to any one of the preceding embodiments, wherein the photodetector unit comprises at least one device configured for photodetection.

[0112] Embodiment 22: The automated PCR analyzer according to any one of the preceding claims, wherein the photodetector unit comprise at least one of a semiconductor photodetector, specifically one or more of a silicon photoconductor, a germanium photoconductor, a gallium arsenide photoconductor or the like, a photodiode, a phototransistor, a CCD sensor, a CMOS sensor, and a photomultiplier.

[0113] Embodiment 23 : The automated PCR analyzer according to any one of the preceding embodiments, wherein the photometer further comprises at least one detector lens, wherein the photometer is configured such that the light emitted from the sample passes the detector lens, specifically after passing the selected filter cell unit.

[0114] Embodiment 24: The automated PCR analyzer according to any one of the preceding embodiments, wherein the excitation light source comprises at least one LED, specifically a broadband LED, more specifically a light conversion LED, more specifically a white LED.

[0115] Embodiment 25: The automated PCR analyzer according to the preceding embodiment, wherein the excitation light source comprises a plurality of LEDs.

[0116] Embodiment 26: The automated PCR analyzer according to the preceding embodiment, wherein the excitation light source comprises the plurality of LEDs arranged in an array, specifically in an m x n matrix, more specifically in a 2 x 2 matrix.

[0117] Embodiment 27: The automated PCR analyzer according to any one of the two preceding embodiments, wherein the plurality of LEDs comprises white LEDs or colored LEDs, specifically colored LEDs of different wavelengths. Embodiment 28: The automated PCR analyzer according to any one of the preceding embodiments, wherein the photometer further comprises at least one excitation light source lens, wherein the photometer is configured such that the excitation light source passes the excitation light source lens onto the selected filter cell unit.

[0118] Embodiment 29: The automated PCR analyzer according to any one of the preceding embodiments, wherein the optical filter elements each comprise an optical filter.

[0119] Embodiment 30: The automated PCR analyzer according to any one of the preceding embodiments, wherein the photometer further comprises at least one object lens, wherein the photometer is configured such that the excitation light and the light emitted from the sample pass the object lens.

[0120] Embodiment 31 : The automated PCR analyzer according to the preceding embodiment, wherein the photometer has an epifluorescence optical design, wherein, in the epifluorescence optical design, the excitation light and the light emitted from the sample pass the same at least one object lens.

[0121] Embodiment 32: The automated PCR analyzer according to any one of the preceding embodiments, wherein the automated PCR analyzer is configured for automatically performing at least one PCR process for determining a presence of at least one pathogen in the sample.

[0122] Embodiment 33: The automated PCR analyzer according to any one of the preceding embodiments, wherein the PCR analyzer is a benchtop PCR analyzer.

[0123] Embodiment 34: The automated PCR analyzer according to any one of the preceding embodiments, wherein the thermocycling apparatus comprises at least one Peltier element.

[0124] Embodiment 35: The automated PCR analyzer according to any one of the preceding embodiments, wherein the temperature modulation comprises a predetermined number of amplification cycles, wherein each amplification cycles comprises at least one denaturation temperature and at least one annealing temperatures. Embodiment 36: The automated PCR analyzer according to any one of the preceding embodiments, wherein the controller is configured for controlling the movable filter cell to selectively position the selected filter cell unit into the working position.

[0125] Embodiment 37: The automated PCR analyzer according to any one of the preceding embodiments, wherein the sample comprises at least one aliquot or aliquant of a bodily fluid.

[0126] Embodiment 38: The automated PCR analyzer according to any one of the preceding embodiments, wherein the optically detectable property of the sample comprises at least one photoluminescence property of the sample.

[0127] Embodiment 39: The automated PCR analyzer according to any one of the preceding embodiments, wherein, in the working position, the selected filter cell unit is positioned such that the light emitted from the sample passes to the photodetector unit, specifically after passing the optical detection filter element.

[0128] Embodiment 40: The automated PCR analyzer according to any one of the preceding embodiments, wherein the excitation light interacts with the optical excitation filter element such that light within an illumination wavelength range passes the optical excitation filter element.

[0129] Embodiment 41 : The automated PCR analyzer according to the preceding embodiment, wherein the excitation light interacts with the dichroic filter such that light within the illumination wavelength range is reflected or transmitted onto the sample.

[0130] Embodiment 42: The automated PCR analyzer according to any one of the preceding embodiments, wherein the light emitted from the sample interacts with the dichroic filter and the optical detection filter element such that light within a detection wavelength range passes the dichroic filter and the optical detection filter element.

[0131] Embodiment 43: A method of automated PCR analysis, wherein the method comprises using the automated PCR analyzer according to any one of the preceding embodiments, wherein the method further comprises: i) subjecting at least one sample, by using the thermocycling apparatus, to at least one temperature modulation controlled by the controller; ii) moving a selected filter cell unit selected from the plurality of filter cell units in the working position; iii) illuminating, by using the excitation light source, the at least one sample via the selected filter cell unit; and iv) detecting, by using the photometer, at least one optically detectable property of the sample.

[0132] Embodiment 44: The method according to the preceding embodiment, further comprising repeating steps i) to iv) for a predetermined number of amplification cycles.

[0133] Embodiment 45: The method according to any one of the preceding method embodiments, wherein the method is computer-controlled.

[0134] Embodiment 46: A computer program comprising instructions which, when the program is executed by the automated PCR analyzer according to any one of the preceding embodiments referring to an automated PCR analyzer, cause the automated PCR analyzer to perform the method according to any one of the preceding embodiments referring to a method.

[0135] Embodiment 47: A computer-readable storage medium, specifically a non-transient computer-readable medium, comprising instructions which, when the instructions are executed by the automated PCR analyzer according to any one of the preceding embodiments referring to an automated PCR analyzer, cause the automated PCR analyzer to perform the method according to any one of the preceding embodiments referring to a method.

[0136] Embodiment 48: A use of an automated PCR analyzer according to any one of the preceding embodiments referring to an automated PCR analyzer, for performing at least one PCR process for determining a presence of at least one pathogen in the sample selected from the group consisting of: hepatitis B virus (HBV); hepatitis C virus (HCV); human immunodeficiency viruses (HIV), in particular HIV-1 and / or HIV-2; West Nile virus (WNV); hepatovirus A (HAV); parvovirus B19 (parvo B 19); hepatitis E virus (HEV); Chikungunya virus (CHIKV); dengue virus (DENV); Babesia; Zika virus; Usutu virus; Herpes simplex virus 1 (HSV-1) and (HSV-2); monkeypox (mpox); hepatitis delta virus (HDV); human papillomavirus (HPV); Chlamydia trachomatis (CT); Neisseria gonorrhoeae (NG); Trichomonas vaginalis (TV); Mycoplasma genitalium (MG); Piling inverting protein gene Neisseria gonorrhoeae (Piv NG); Cytomegalovirus (CMV); Epstein-Barr virus (EBV); BK polyomavirus (BKV); Mycobacterium tuberculosis (MTB); M. avium complex (MAC); M. avium-intracellulare (MAI); SARS-CoV-2; Influenza A; Influenza B; respiratory syncytial virus (RSV); C. difficile; Norovirus; Adenovirus (ADV); human Metapneumovirus (hMPV); Enterovirus-Rhinovirus (EV- RV); human parainfluenza viruses 1 - 4 (HPIV); Methicillin-resistent Staphylococcus aureus (MRSA); Staphylococcus aureus (SA); human leukocyte antigen B27 (HLA- B27); Group A Strep.

[0137] Short description of the Figures

[0138] Further optional features and embodiments will be disclosed in more detail in the subsequent description of embodiments, preferably in conjunction with the dependent claims. Therein, the respective optional features may be realized in an isolated fashion as well as in any arbitrary feasible combination, as the skilled person will realize. The scope of the invention is not restricted by the preferred embodiments. The embodiments are schematically depicted in the Figures. Therein, identical reference numbers in these Figures refer to identical or functionally comparable elements.

[0139] In the Figures:

[0140] Figure 1 A shows a first embodiment of an automated polymerase chain reaction

[0141] (PCR) analyzer in a schematic view;

[0142] Figure IB shows a second embodiment of an automated PCR analyzer in a schematic view;

[0143] Figure 2 shows a third embodiment of an automated PCR analyzer in a schematic view;

[0144] Figure 3 shows a schematic sketch of an embodiment of an automated PCR analyzer;

[0145] Figure 4 shows the embodiment of the automated PCR analyzer of Figure IB in a perspective view; Figures 5 A and 5B show an embodiment of a movable filter cell;

[0146] Figures 6A and 6B show the embodiment of the photometer of Figure IB in rear view (Figure 6A) and in front view (Figure 6B); and

[0147] Figure 7 shows a flow chart of a method of automated PCR analysis.

[0148] Detailed description of the embodiments

[0149] Figure 1A shows an exemplary embodiment of an automated polymerase chain reaction (PCR) analyzer 110 for analyzing at least one sample 112 in a schematic view. Specifically, in the Figures, the photometer 118 is shown in more detail, whereas the other parts of the PCR analyzer are only shown schematically. The automated PCR analyzer 110 may be, as an example, a benchtop PCR analyzer. The sample 112 may comprise a fluid sample obtained from, for example, a bodily fluid such as blood, plasma, serum, urine, saliva, interstitial fluid, or other types of body fluids. The optically detectable property of the sample 112 may comprise at least one photoluminescence property of the sample 112. The automated PCR analyzer 110 may be configured for automatically performing at least one PCR process for determining a presence of at least one pathogen in the sample 112. The pathogen, as an example, may be selected from the group consisting of: hepatitis B virus (HBV); hepatitis C virus (HCV); human immunodeficiency viruses (HIV), in particular HIV-1 and / or HIV-2; West Nile virus (WNV); hepatovirus A (HAV); parvovirus B19 (parvo B 19); hepatitis E virus (HEV); Chikungunya virus (CHIKV); dengue virus (DENV); Babesia; Zika virus; Usutu virus; Herpes simplex virus 1 (HSV-1) and (HSV-2); monkeypox (mpox); hepatitis delta virus (HDV); human papillomavirus (HPV); Chlamydia trachomatis (CT); Neisseria gonorrhoeae (NG); Trichomonas vaginalis (TV); Mycoplasma genitalium (MG); Piling inverting protein gene Neisseria gonorrhoeae (Piv NG); Cytomegalovirus (CMV); Epstein- Barr virus (EBV); BK polyomavirus (BKV); Mycobacterium tuberculosis (MTB); M. avium complex (MAC); M. avium-intracellulare (MAI); SARS-CoV-2; Influenza A; Influenza B; respiratory syncytial virus (RSV); C. difficile; Norovirus; Adenovirus (ADV); human Met- apneumovirus (hMPV); Enterovirus-Rhinovirus (EV-RV); human parainfluenza viruses 1 - 4 (HPIV); Methicillin-resi stent Staphylococcus aureus (MRSA); Staphylococcus aureus (SA); human leukocyte antigen B27 (HLA-B27); Group A Strep. The automated PCR analyzer 110 comprises at least one controller 114. The automated PCR analyzer 110 further comprises at least one thermocycling apparatus 116 configured for subjecting the sample 112 to at least one temperature modulation controlled by the controller 114. The thermocycling apparatus 116 may be configured for at least one of heating and cooling the sample 112. For example, the thermocycling apparatus 116 may comprise at least one Peltier element. Other examples are, however, also feasible.

[0150] The automated PCR analyzer comprises at least one photometer 118 configured for detecting at least one optically detectable property of the sample 112. The photometer 118 comprises one excitation light source 120 configured for illuminating the sample 112 with excitation light 122. In the embodiment shown in Figure 1 A, the excitation light source 120 may comprise a plurality of LEDs. The LEDs may be white LEDs. The plurality of LEDs may be arranged in an array, specifically in a 2 x 2 matrix.

[0151] The photometer 118 further comprises at least one photodetector unit 124 configured for detecting light 123 emitted from the sample 112. The photodetector unit 124 may comprise a semiconductor photodetector, specifically a silicon photoconductor. Further, the photometer 118 comprises a movable filter cell 126 controllable by the controller 114. The movable filter cell 126 comprises a plurality of filter cell units 128, wherein each filter cell unit 128 comprises at least one optical excitation filter element 130, at least one dichroic filter 132, at least one optical detection filter element 134 and at least one the aperture stop 174, as will be outlined in further detail below. The aperture stop 174 is not visible in the view of Figure 1A. In the exemplary embodiment of Figure 1A, the filter cell unit 128 may comprise the optical excitation filter element 130, the dichroic filter 132 and the optical detection filter element 134 in a single filter cell unit 128. The optical excitation filter element 130 and the optical detection filter element 134 may each comprise at least one optical element having wavelength- selecting properties, such as at least one optical filter. The dichroic filter 132 may comprise at least one optical element having wavelength-dependent reflecting, deflecting and transmitting properties.

[0152] The excitation light 122 may comprise light propagating from the excitation light source 120 to the sample 112, before and after passing the selected filter cell unit 128, specifically before and after being optically filtered by the excitation filter 130 and the dichroic filter 132. The excitation light 122 may interact with the optical excitation filter element 130 such that light within an illumination wavelength range passes the optical excitation filter element 130. The excitation light 122 may interact with the dichroic filter 132 such that light within the illumination wavelength range is reflected onto the sample 112. The light 123 emitted from the sample 112 may comprises light propagating from the sample 112 to the photodetector unit 124, before and after passing the selected filter cell unit 128, specifically before and after being filtered by the dichroic filter 132 and the detection filter element 134. The light 123 emitted from the sample 112 may interact with the dichroic filter 132 and the optical detection filter element 134 such that light within a detection wavelength range passes the dichroic filter 132 and the optical detection filter element 134.

[0153] As shown in Figure 1 A, the photometer 118 may further comprise at least one detector lens 138. The photometer 118 may be configured such that the light emitted from the sample 112 passes the detector lens 138, specifically after passing the selected filter cell unit 128. Further, the photometer 118 may comprise at least one excitation light source lens 140. The photometer 118 may be configured such that the excitation light source 120 passes the excitation light source lens 140 onto the selected filter cell unit 128. Alternatively or in addition, the photometer 118 further comprises at least one object lens 142. The photometer 118 may be configured such that the excitation light 122 and the light 123 emitted from the sample 112 pass the object lens 142. For example, as can be seen in Figure 1 A, the photometer 118 may have an epifluorescence optical design. In the epifluorescence optical design, the excitation light 122 and the light 123 emitted from the sample 112 may pass the same at least one object lens 142.

[0154] The photometer 118 comprises a working position for the filter cell units 128. The movable filter cell 126 is configured for selectively positioning a selected filter cell unit 128 selected from the plurality of filter cell units 128 in the working position. In the working position, the selected filter cell unit 128 is positioned such that the excitation light 122 interacts with the optical excitation filter element 130, the dichroic filter 132 and the aperture stop 174 of the selected filter cell unit 128 and that the light 123 emitted from the sample 112 interacts with the dichroic filter 132, the aperture stop 174 and the optical detection filter element 134 of the selected filter cell unit 128. For example, the controller 114 may be configured for controlling the movable filter cell 126 to selectively position the selected filter cell unit 128 into the working position.

[0155] Further, as shown in Figure 1 A, the automated PCR analyzer 110, in this exemplary embodiment, may comprise at least one reference element 144. The photometer 118 may be configured for illuminating the reference element 144 with reference excitation light 146 from the excitation light source 120. The photometer 118 may be further configured for detecting the reference excitation light 146 on the reference element 144. The reference excitation light 146 may comprise part of the excitation light 122 after passing the optical excitation filter element 130 and the dichroic filter 132 of the selected filter cell unit 128. As an example, the reference element 144 may comprise at least one reference photodetector 148. The reference photodetector 148 may comprise a semiconductor photodetector, specifically a silicon photoconductor. Each filter cell unit 128 may further comprise at least one optical reference filter element 149. In the working position, the selected filter cell unit 128 may be positioned such that the reference excitation light 146 interacts with the optical reference filter element 149. Specifically, in the working position, the selected filter cell unit 128 may be positioned such that the reference excitation light 146 illuminates the optical reference filter element 149 and the reference excitation light 146 as transmitted by the optical reference filter element 149 illuminates the reference photodetector 148. The reference element 144 may further comprise at least one reference lens 150. The photometer 118 may be configured such that the reference excitation light 146 passes the reference lens 150, specifically after passing the selected filter cell unit 128.

[0156] In Figure IB, a second exemplary embodiment of an automated PCR analyzer 110 is shown in a schematic view. The second embodiment of the automated PCR analyzer 110 shown in Figure IB largely corresponds to the first embodiment of the automated PCR analyzer 110 shown in Figure 1A. Thus, for a detailed description of the automated PCR analyzer 110, reference is made to the description of Figure 1A. As can be seen in Figure IB, a distance between the movable filter cell 126, specifically in between the selected filter cell unit 128, and the sample 112, may be increased, e.g. up to 20 mm, such as by using an object lens 142 having appropriate focal length.

[0157] In Figure 2, a third exemplary embodiment of an automated PCR analyzer 110 is shown in a schematic view. The third embodiment of the automated PCR analyzer 110 shown in Figure 2 largely corresponds to the first embodiment of the automated PCR analyzer 110 shown in Figure 1 A. Thus, for a detailed description of the automated PCR analyzer 110, reference is made to the description of Figure 1 A. As shown in Figure 2, each filter cell unit 128 may comprise at least one first submodule 158 and at least one second submodule 160. The first submodule 158 may comprise the optical excitation filter element 130 and the dichroic filter 132. The second submodule 160 may comprise the optical detection filter element 134. The first 158 and the second submodule 160 may be movable independent from each other, e.g. by using an additional rail and an additional motor. The first 158 and the second submodule 160 may be connectable such as to provide a common optical path for the excitation light 122 and the light 123 from the sample 112. The first 158 and second submodule 160 being movable independent from each other may allow multiplexing of channels, i.e. combining a selected optical path defined by the optical excitation filter element 130 and the dichroic filter 132 with a selected optical path defined by the optical detection filter element 134. The multiplexing of channels may increase flexibility of the photometer 118 with regard to the measurement channels.

[0158] In Figure 3, a schematic sketch of an automated PCR analyzer 110 is shown using a block diagram for a higher level of abstraction. The arrows with solid lines (denoted by reference number 162) may show an optical path of the excitation light 122 from the excitation light source 120 to the sample 112. The arrows with dashed lines (denoted by reference number 164) may show an optical path of the light 123 emitted from the sample 112, e.g. comprising emission from the sample 112 in the form of photoluminescence, from the sample 112 to the photodetector unit 124. As can be seen further in Figure 3, the optical path of the reference excitation light 146 comprising part of the excitation light 122 after passing the optical excitation filter element 130 and the dichroic filter 132 of the selected filter cell unit 128 may comprise an optical path from the excitation light source 120 to the reference element (denoted by reference number 166).

[0159] Figure 4 shows the exemplary second embodiment of the automated PCR analyzer 110 of Figure IB in a perspective view. Specifically, Figure 4 shows a perspective sectional view through a center plane of the photometer 118 such that the selected filter cell unit 128 is visible. For a detailed description of the automated PCR analyzer 110, reference is made to the description of Figure IB.

[0160] Figure 5A and Figure 5B show an exemplary embodiment of a movable filter cell 126. The movable filter cell 126 as shown in Figures 5 A and 5B may be used in any one of the exemplary embodiments of the automated PCR analyzer 110 shown in Figures 1A to 4. However, alternatively, other embodiments of the movable filter cell 126, such as a filter wheel, may also be feasible. Figure 5A shows the movable filter cell 126 in a perspective view, wherein Figure 5B shows an exploded view of the movable filter cell 126. As can be seen in Figures 5A and 5B, the movable filter cell 126 may comprise a linear stage 168 carrying the plurality of filter cell units 128. The linear stage 168 may comprise at least two side parts 170 having the plurality of filter cell units 128 arranged in between the two side parts 170. The linear stage 168 may further comprise plain bearings 172 directly integrated into the at least two side parts 170.

[0161] Further, each filter cell unit 128 may comprise at least one aperture stop 174, specifically at least one elliptically shaped aperture stop. The aperture stops 174 can be seen best in Figure 5B. The aperture stop 174, in this example, may be arranged in the beam path of the excitation light 122 and the light 123 emitted from the sample 112, specifically on top of the dichroic filter 132 as shown in Figure 5B.

[0162] In this exemplary embodiment, the movable filter cell 126 may comprise six filter cell units 128. However, other numbers of filter cell units 128, such as at least two filter cell units 128, specifically at least four filter cell units 128 or even more, may also be feasible.

[0163] Figures 6A and 6B show the exemplary second embodiment of the photometer 118 as shown in Figure IB in a perspective rear view (Figure 6 A) and in a perspective front view (Figure 6B). For a detailed description of the automated PCR analyzer 110, reference is made to the description of Figure IB. The movable filter cell 126, in this example, may comprise the linear stage 168 as exemplarily shown in Figures 5 A and 5B.

[0164] As can be seen in Figures 6A and 6B, the photometer 118 may comprise at least one guide rod 175 at least partially received in the plain bearings 172 of the linear stage 168 for guiding movement of the movable filter cell 126. The photometer 118 may further comprise at least one linear actuator 176, specifically at least one toothed belt drive 178, for moving the movable filter cell 126. The actuator 176 may be configured for moving the filter cell units 128 into the working position and out of the working position.

[0165] In Figure 7, a flow chart of a method of automated PCR analysis is shown. The method comprises using the automated PCR analyzer 110 according to the present invention, such as according to any one of the exemplary embodiments shown in Figures 1A to 4 and / or according to any other embodiments disclosed herein.

[0166] The method comprises the following steps that may be performed in the given order. However, a different order may also be possible. In particular, one, more than one or even all of the method steps may be performed once or repeatedly. Further, the method steps may be performed successively or, alternatively, one or more of the method steps may be performed in a timely overlapping fashion or even in a parallel fashion and / or in a combined fashion. The method may further comprise additional method steps that are not listed.

[0167] The method comprises the following steps: i) (denoted by reference number 180) subjecting at least one sample 112, by using the thermocycling apparatus 116, to at least one temperature modulation controlled by the controller 114; ii) (denoted by reference number 182) moving a selected filter cell unit 128 selected from the plurality of filter cell units 128 in the working position; iii) (denoted by reference number 184) illuminating, by using the excitation light source 120, the at least one sample 112 via the selected filter cell unit 128; and iv) (denoted by reference number 186) detecting, by using the photometer 118, at least one optically detectable property of the sample 112.

[0168] The steps i) (denoted by reference number 180) to iv) (denoted by reference number 186) may also be repeated for a predetermined number of amplification cycles, specifically for a number of 1-50 cycles, as indicated by the dashed line in Figure 7. The method may also be computer-controlled.

[0169] List of reference numbers automated polymerase chain reaction (PCR) analyzer sample controller thermocycling apparatus photometer excitation light source excitation light light emitted from the sample photodetector unit movable filter cell filter cell unit optical excitation filter element dichroic filter optical detection filter element detector lens excitation light source lens object lens reference element reference excitation light reference photodetector optical reference filter element reference lens first submodule second submodule optical path of the excitation light optical path of the light emitted from the sample optical path of the reference excitation light linear stage side part plain bearing aperture stop guide rod actuator toothed belt drive subjecting at least one sample to at least one temperature modulation 182 moving a selected filter cell unit in working position

[0170] 184 illuminating the at least one sample via the selected filter cell unit

[0171] 186 detecting at least one optically detectable property of the sample

Claims

AMENDED CLAIMS received by the International Bureau on 14 October 2025 (14.10.2025)1. An automated polymerase chain reaction (PCR) analyzer (110) for analyzing at least one sample (112), comprising: at least one controller (114); at least one thermocycling apparatus (116) configured for subjecting the sample (112) to at least one temperature modulation controlled by the controller (114); at least one photometer (118) configured for detecting at least one optically detectable property of the sample (112), the photometer (118) comprising at least one excitation light source (120) configured for illuminating the sample (112) with excitation light (122), the photometer (118) further comprising at least one photodetector unit (124) configured for detecting light (123) emitted from the sample (112), the photometer (118) further comprising a movable filter cell (126) controllable by the controller (114), the movable filter cell (126) comprising a plurality of filter cell units (128), each filter cell unit (128) comprising at least one optical excitation filter element (130), at least one dichroic filter (132) at least one optical detection filter element (134) and at least one aperture stop (174), wherein the movable filter cell (126) comprises a working position for the filter cell units (128), wherein the movable filter cell (126) is configured for selectively positioning a selected filter cell unit (128) selected from the plurality of filter cell units (128) in the working position, wherein, in the working position, the selected filter cell unit (128) is positioned such that the excitation light (122) interacts with the optical excitation filter element (130), the dichroic filter (132) and the aperture stop (174) of the selected filter cell unit (128) and that the light (123) emitted from the sample (112) interacts with the dichroic filter (132), the aperture stop (174) and the optical detection filter element (134) of the selected filter cell unit (128), wherein the photometer (118) further comprises at least one object lens (142), wherein the photometer (118) is configured such that the excitation light (122) and the light (123) emitted from the sample (112) pass the object lens (142), wherein the photometer (118) has an epifluorescence optical design, wherein, in the epifluorescence optical design, the excitation light (122)and the light (123) emitted from the sample (112) pass the same at least one object lens (142); further comprising at least one reference element (144), wherein the photometer (118) is configured for illuminating the reference element (144) with reference excitation light (122) from the excitation light source (120) and wherein the photometer (118) is further configured for detecting the reference excitation light (146) on the reference element (144), wherein the reference element (144) comprises at least one reference photodetector (148), wherein each filter cell unit (128) further comprises at least one optical reference filter element (149), wherein, in the working position, the selected filter cell unit (128) is positioned such that the reference excitation light (146) interacts with the optical reference filter element (149).

2. The automated PCR analyzer (110) according to the preceding claim, wherein each filter cell unit (128) comprises the optical excitation filter element (130), the dichroic filter (132), the optical detection filter element (134) and the aperture stop (174) in a single filter cell unit (128).

3. The automated PCR analyzer (110) according to any one of the preceding claims, wherein each filter cell unit (128) comprises at least one first submodule (158) and at least one second submodule (160), wherein the first submodule (158) comprises the optical excitation filter element (130), wherein the second submodule (160) comprises the optical detection filter element (134), wherein the first (158) and the second submodule (160) are movable independent from each other.

4. The automated PCR analyzer (110) according to any one of the preceding claims, wherein the movable filter cell (126) comprises at least two filter cell units (128), wherein the optical excitation filter element (130) and the optical detection filter element (134) of each filter cell unit (128) are configured for filtering light in a specific wavelength range, wherein the specific wavelength range is different for each filter cell unit (128).

5. The automated PCR analyzer (110) according to any one of the preceding claims, wherein the movable filter cell (126) comprises at least one of a linear stage (168) and a filter wheel carrying the plurality of filter cell units (128).

6. The automated PCR analyzer (110) according to any one of the preceding claims, wherein the movable filter cell (126) further comprises at least one actuator (176) for moving the filter cell units (128) into the working position and out of the working position.

7. The automated PCR analyzer (110) according to any one of the preceding claims, wherein the photometer (118) further comprises at least one detector lens (138), wherein the photometer (118) is configured such that the light (123) emitted from the sample (112) passes the detector lens (138).

8. The automated PCR analyzer (110) according to any one of the preceding claims, wherein the photometer (118) further comprises at least one excitation light source lens (140), wherein the photometer (118) is configured such that the excitation light source (120) passes the excitation light source lens (140) onto the selected filter cell unit (128).

9. The automated PCR analyzer (110) according to any one of the preceding claims, wherein the PCR analyzer (110) is a benchtop PCR analyzer.

10. A method of automated PCR analysis, wherein the method comprises using the automated PCR analyzer (110) according to any one of the preceding claims, wherein the method further comprises: i) subjecting at least one sample (112), by using the thermocycling apparatus (116), to at least one temperature modulation controlled by the controller (114); ii) moving a selected filter cell unit (128) selected from the plurality of filter cell units (128) in the working position; iii) illuminating, by using the excitation light source (120), the at least one sample (112) via the selected filter cell unit (128); and iv) detecting, by using the photometer (118), at least one optically detectable property of the sample (112).

11. A computer program comprising instructions which, when the program is executed by the automated PCR analyzer (110) according to any one of the preceding claims referring to an automated PCR analyzer (110), cause the automated PCR analyzer (110) to perform the method according to any one of the preceding claims referring to a method.

12. A computer-readable storage medium comprising instructions which, when the instructions are executed by the automated PCR analyzer (110) according to any one of the preceding claims referring to an automated PCR analyzer (110), cause the automated PCR analyzer (110) to perform the method according to any one of the preceding claims referring to a method.

13. A use of an automated PCR analyzer (110) according to any one of the preceding claims referring to an automated PCR analyzer (110), for performing at least one PCR process for determining a presence of at least one pathogen in the sample (112) selected from the group consisting of: hepatitis B virus (HBV); hepatitis C virus (HCV); human immunodeficiency viruses (HIV), in particular HIV- 1 and / or HIV-2; West Nile virus (WNV); hepatovirus A (HAV); parvovirus B19 (parvo B 19); hepatitis E virus (HEV); Chikungunya virus (CHIKV); dengue virus (DENV); Babesia; Zika virus; Usutu virus; Herpes simplex virus 1 (HSV-1) and (HSV-2); monkeypox (mpox); hepatitis delta virus (HDV); human papillomavirus (HPV); Chlamydia trachomatis (CT); Neisseria gonorrhoeae (NG); Trichomonas vaginalis (TV); Mycoplasma genitalium (MG); Piling inverting protein gene Neisseria gonorrhoeae (Piv NG); Cytomegalovirus (CMV); Epstein-Barr virus (EBV); BK polyomavirus (BKV); Mycobacterium tuberculosis (MTB); M. avium complex (MAC); M. avium-intracellulare (MAI); SARS- CoV-2; Influenza A; Influenza B; respiratory syncytial virus (RSV); C. difficile; Norovirus; Adenovirus (ADV; human Metapneumovirus (hMPV); Enterovirus-Rhinovi- rus (EV-RV); human parainfluenza viruses 1 - 4 (HPIV); Methicillin-resi stent Staphylococcus aureus (MRSA); Staphylococcus aureus (SA); human leukocyte antigen B27 (HLA-B27); Group A Strep.

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