FLEXFOIL AND MICROFLUIDIC ARRANGEMENT
Patent Information
- Application Number
- DE112022002144
- Authority / Receiving Office
- DE · DE
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2021-07-08
- Filing Date
- 2022-05-18
- Publication Date
- 2025-10-30
- Estimated Expiration
- 2042-05-18
Smart Images

Figure 00000000_0000_ABST
Abstract
Description
Territory of Revelation
[0001] The present invention relates to a flexible film for sealing a microfluidic cartridge and a microfluidic arrangement comprising, for example, a reading device for reading the microfluidic cartridge. background
[0002] The design of microfluidic cartridges plays a crucial role in the successful development of a diagnostic system, where ease of use, throughput, and cost per test are critical factors. This is especially true for point-of-care testing (POCT) applications, where the cartridge also serves as a simple and intuitive user hardware interface and where optical detection is used to read the microfluidic cartridge.
[0003] At low signal strengths, such as for photon counting, which is used in most sensitive biodiagnostic reactions, integration with close proximity can be important, since light intensities with 1 / R 2 decrease, where R is the distance between a sample in a microfluidic cartridge and a detector. In practice, however, it is common to rely on integration with loose, large components, such as diodes or ASICs spaced apart, with optical components (lenses, optical filters, etc.) in between, allowing the cartridge to be removed. Sometimes ASICs are arranged on one side of the microfluidic cartridge, with metal tracks also present.
[0004] At least for the following reasons, it can be important to keep R as small as possible. 1) Signal loss caused by a large distance (> detector diameter) between the sample and detector, even with optics in between. 2) Due to the size of optics and / or sensors, it is not possible to miniaturize the detection section. This is necessary to reduce costs and introduce it into the field of point-of-care testing. 3) In the case of multiparametric detection on the microfluidic cartridge, which requires multiple sensors, alignment and yield problems arise with each detector placement. For example, if each array yields 95%, then with 16 sensors, the yield of the array would be (0.95) 16= 0.44. And 4) in the case of multiparametric detection with a sensor ASIC, to minimize crosstalk between the different sensors on the ASIC. More often, a circuit board and a separate detection system are used, with additional optics and photodiodes, or photomultipliers are used (for photon counting).
[0005] US 10 156 511 B2 concerns a photodetector circuit with multi-layer wiring.
[0006] DE 102 22 478 A1 relates to a distribution element for liquids and gases.
[0007] US 2013 / 0156642A1 concerns an optical detection system for the detection of molecules.
[0008] US 11 067 535 B2 concerns a fluorescence test system.
[0009] US 7 524 459 B2 relates to an integrated measuring arrangement with an optical detection system and a microfluidic system.
[0010] US 2019 / 0 247 854 A1 concerns a cartridge with integrated sensors.
[0011] One of the objectives of the present disclosure is to provide a microfluidic system which enables a miniaturized, cost-effective design and improved detection.
[0012] These problems are solved by the subject matter of the independent claims. Further developments and embodiments are described in the dependent claims. Brief description
[0013] The following describes an improved concept in the field of microfluidics. One aspect involves the use of a single flexible film for electrical wiring and contacting an integrated photodetector circuit (or ASIC), as well as for sealing the detection wells of the microfluidic cartridge. Further aspects include sealing the microfluidic cartridge and sensor wells (detection chambers), and the presence of optically transparent windows at the sensor well locations. The flexible film incorporates electrical wiring and provides means for mounting integrated circuits, such as the integrated photodetector circuit, to the electrical wiring and / or pads. The flexible film can also include contact points for a readout socket.
[0014] The flexible film for sealing a microfluidic cartridge comprises a flexible carrier film and an integrated photodetector circuit. The integrated photodetector circuit includes at least one photodetector. The carrier film includes at least one optically transparent window or cutout. The integrated photodetector circuit is positioned on the carrier film such that the photodetector is aligned with the optically transparent window. Finally, the integrated photodetector circuit is electrically and functionally connected to the flexible carrier film.
[0015] The term "carrier film" refers to a part of the flexible film, which comprises a flexible material such as a foil or film. The carrier film may be supplemented with electrical wiring to form the flexible film. Furthermore, components such as the integrated photodetector circuitry can be electrically and functionally connected to the flexible carrier film to form the flexible film.
[0016] Using a single flexible film for electrical wiring, contact with integrated circuits, and sealing the microfluidic cartridge offers several advantages. It allows for minimal separation between the liquid sample in detection chambers and the photodetector. Furthermore, the use of a flexible film can eliminate the need for an additional sealing film, meaning at least one film thickness is reduced. In other words, the flexible film can act as a sealing film, with the carrier film sealing, for example, a microfluidic cartridge. Finally, the flexible film enables multichannel detection with a single placement of an integrated photodetector circuit, resulting in lower assembly costs and high yield with reduced optical crosstalk.Minimized crosstalk between channels is achieved through a thinner film, a lower R-value, and the use of opaque materials. Assembly is simplified due to fewer steps (e.g., one less film). The resulting microfluidic array can be more light-tight. Integrated circuits, such as a detector ASIC and other ASICs, can be integrated onto the same flexible film, along with contacts like SD card contacts. A channel can be considered a separate detection well in microfluidics, which can be monitored, for example, by an optical (sense-SPAD array) sensor covering a biodiagnostic parameter.
[0017] In at least one embodiment, the substrate film comprises an array of optically transparent windows. The integrated photodetector circuit comprises an array of photodetectors. The integrated photodetector circuit is arranged on the substrate such that each photodetector is aligned with a respective optically transparent window.
[0018] During operation, a light signal originating from liquid in the detection chambers can only be detected through the optically transparent windows. Crosstalk can be reduced.
[0019] In at least one embodiment, the carrier film comprises optically transparent and optically opaque material. The carrier film is structured such that sections of the carrier film comprising the optically transparent material form one or more optically transparent windows. Additionally, or alternatively, sections of the carrier film have cutouts. This structuring provides a means to further reduce crosstalk. In fact, the use of the structured sections eliminates the need for additional optical barriers, which would otherwise introduce additional thickness. Ultimately, the signal-to-noise ratio can be improved.
[0020] In at least one embodiment, the carrier film comprises at least one layer of optically transparent material and at least one layer of optically opaque material. The carrier film is structured such that sections of the layers form one or more optically transparent windows. These layers provide a high degree of freedom for creating structures that effectively reduce crosstalk.
[0021] In at least one embodiment, the flexible film further comprises an integrated driver circuit. The integrated driver circuit is arranged on the carrier film. Furthermore, the integrated driver circuit is electrically and functionally connected to the flexible carrier film. During operation, the integrated driver circuit controls the microfluidic cartridge and / or the integrated photodetector circuit.
[0022] In at least one embodiment, the flexible film further comprises electrical wiring and an interface. The wiring can be operated to establish an electrical connection to the integrated photodetector circuit and / or the integrated driver circuit via the interface. The wiring can primarily be used to establish electrical contact with and operate the integrated circuits of the flexible film. However, the wiring can also be used as a heating element to set, control, or maintain a constant temperature or elevated temperature in the detection chambers.
[0023] In at least one embodiment, the carrier film comprises one or more adhesive bonds to establish contact between the carrier film and the integrated photodetector circuit and / or the integrated driver circuit. Simultaneously, the adhesive bonds can be used to reduce optical crosstalk between the photodetectors on the integrated photodetector circuit. Alternatively, the integrated photodetector circuit and / or the integrated driver circuit are embedded in the carrier film. According to another alternative, a structured spacer structure is used to establish contact between the carrier film and the integrated photodetector circuit and / or the integrated driver circuit and to reduce optical crosstalk between the photodetectors on the integrated photodetector circuit.
[0024] In at least one embodiment, the carrier film has a thickness between 10 and 200 µm. This allows for a small distance between the photodetectors and a cartridge.
[0025] The microfluidic assembly comprises a microfluidic cartridge, which includes a cartridge body. The cartridge body has at least one detection chamber connected to a microchannel to hold a liquid to be tested. The microfluidic assembly also includes a flexible film. This film is attached to the microfluidic cartridge to seal the detection chambers and / or microchannels. The microfluidic cartridge is positioned on the flexible film such that one or more of the photodetectors of the integrated photodetector circuit are aligned with a respective detection chamber. The microfluidic cartridge can extend beyond the area used for the detection chambers.
[0026] During operation, the microfluidic cartridge receives the liquid to be tested, e.g., via the microchannel. The liquid can then be fed into the detection chamber via the connected microchannel. The photodetector can detect a light signal, such as fluorescence or chemiluminescence, from the liquid to be tested, which is present in the detection chamber.
[0027] In at least one embodiment, the cartridge body comprises several detection chambers, each connected to a microchannel to hold one or more liquids to be tested. Each photodetector on the integrated photodetector circuit can be positioned and aligned directly opposite a detection chamber on the microfluidic cartridge.
[0028] The microfluidic cartridge can be considered a multi-channel cartridge that allows for the testing and sampling not just of a single liquid, but either a larger quantity of one liquid or several different liquids. Due to the alignment of the photodetectors with their respective detection chambers, the photodetectors can operate in parallel to record light signals, such as fluorescence or luminescence, from the respective liquids. The microfluidic cartridge can incorporate detection chambers on different levels to enable the simultaneous testing of even more liquids.
[0029] In at least one embodiment, the cartridge body comprises an optically opaque and / or non-reflective material. These materials help to reduce crosstalk.
[0030] In at least one embodiment, the detection chambers and / or microchannels in the cartridge body are designed as open cavities. These cavities are closed and sealed by means of the flexible film described above. The shutter film can be used in addition to the flexible film to seal the detection chamber(s) and / or microchannels. For example, the shutter film can have corresponding sections, optical windows, and / or cutouts that correspond to those of the flexible film, and vice versa. In this way, the shutter film and / or the flexible film can be aligned with the detection chambers and photodetectors in the same manner.
[0031] The microfluidic cartridge can be used as a single (disposable) component, with electronic components mounted on the flexible film or any other suitable substrate. However, the microfluidic cartridge can also be implemented with the electronic components mounted on the flexible film, as explained above. In this way, the microfluidic cartridge can be disposed of along with the flexible film.
[0032] For example, the microfluidic cartridge sealed with the shutter film can be inserted into a reader above the electronic flex film, which includes the integrated photodetector circuitry and / or integrated control circuitry, in such a way that the detection chambers and the corresponding photodetectors are aligned with each other. This allows for the close proximity of optical barriers and their use to prevent optical crosstalk between the pairs of detection chambers and photodetectors.
[0033] In at least one embodiment, the microfluidic arrangement comprises a reader. The reader further comprises an opening for inserting the microfluidic cartridge into a measuring position to perform a fluorescence and / or chemiluminescence measurement.
[0034] The microfluidic measuring device can be implemented to perform either fluorescence-based or chemiluminescence-based measurements. For the former, the reader can be equipped with an excitation light source to illuminate one or more detection chambers and / or a processing unit to control the light source. This allows the photodetectors to register fluorescence reflected from the liquid in the detection chambers. In such a case, the photodetectors are equipped with the necessary optical filter arrangement to block the excitation light wavelength and detect the fluorescence wavelength.
[0035] For the second type of measurement, the reader does not necessarily need to be equipped with a light source, as excitation may not be required to trigger luminescence. However, the microfluidic cartridge, i.e., microchannels, can be used to introduce chemical compounds to trigger chemical reactions that produce a chemiluminescent response. The liquids can already be present in a freeze-dried chemical composition within the microfluidic detection chamber (or previously within the microfluidic system / channels). Triggering can be achieved, for example, by adding a sample fluid (e.g., urine, saliva, blood) from outside the cartridge.
[0036] The processing unit can control and / or process the measurements. The reader can be equipped to perform one or both of the types of measurements described above.
[0037] Further aspects of this disclosure concern the following. The integrated photodetector circuit, e.g., a photon counter-detector ASIC, can be assembled near detection chambers of a microfluidic cartridge. Sections of the cartridge and / or flexible film should be made of opaque material, e.g., black, with optically transparent windows, or, via cutouts, in direct contact with a passivation layer of the integrated circuits.
[0038] The proposed concept enables single-channel or multi-channel detection with a single ASIC placement on the microfluidic cartridge. This results in low assembly costs, high yield, fewer alignment problems, and minimized crosstalk between channels. Some of the proposed measures are: a) minimum film thicknesses used: from 200 µm down to ~10 µm; b) the use of black coatings or paints and / or black adhesives and / or black shapes; c) the use of non-reflective (black) coatings or paints; d) photopic and pigmented films.
[0039] The proposed concept allows for minimizing the distance between the sample and the detector, thus increasing sensitivity. This is facilitated by the film thicknesses used, ranging from 200 µm down to approximately 10 µm, and the need to use fewer layers to reduce the distance. This makes individual layers multifunctional. The functions of the proposed flexible film include sealing microfluidic wells, electrical wiring, electrical heating, integration of heat sinks, and / or integration of cooling elements.
[0040] However, the concept discussed here can also be implemented without flex film, for example with substrates such as laminate or circuit boards, even with FAM packages.
[0041] The number of assembly steps can be reduced by using fewer components and fewer layers. A light-tight arrangement can be achieved, enabling highly sensitive photon counting detection, e.g., everything in black, etc. Some or all components can be disposable and implemented in a small form factor (like an SD card, or smaller).
[0042] The flexible film and / or the carrier allows for the integration of a heat sink or cooler (for example, a smallest Peltier element of 1 mm). 2 (which may be sufficient to significantly increase sensitivity). A flexible film can be used to combine integrated electrical wiring for ASICs and an integrated heater with the sealing of the microfluidic cartridge.
[0043] The following description of figures of exemplary embodiments of the invention, as well as further examples, can further illustrate and explain aspects of the improved concept. Components and parts with the same structure or function are provided with equivalent reference numerals. If components and parts in different figures correspond to each other with respect to their function, their description is not necessarily repeated for each of the subsequent figures. Brief description of the drawings
[0044] The figures show: Fig. 1 an embodiment of a microfluidic arrangement, Fig. 2 another embodiment of a microfluidic arrangement, Fig. 3 another embodiment of a microfluidic arrangement, Fig. 4 an example of a microfluidic cartridge, Fig. 5 an example of a flex film from a microfluidic cartridge, Fig. 6 Another example of a flex film from a microfluidic cartridge, and Fig. 7 another example of a flex film from a microfluidic cartridge, and the Fig. 8A, Fig. 8B is an embodiment of a microfluidic arrangement.
[0045] Fig. Figure 1 shows an embodiment of a microfluidic arrangement. The arrangement comprises a microfluidic cartridge and a flexible film.
[0046] The flexible film also includes a CFL carrier film. This carrier film is, for example, a plastic film and has a thickness between 10 and 200 µm. Furthermore, the flexible film includes electrical wiring (WIR) arranged on the carrier film. Alternatively, the wiring can also be embedded in the carrier film. The wiring can be connected to an interface (not shown) to connect the flexible film and its components to, for example, a reader.
[0047] The CFL carrier film is structured into different sections. Some sections contain optically transparent material, forming optically transparent windows (OTW). Other sections contain optically opaque material.
[0048] In this embodiment, the carrier film is structured on the inside. For example, photopic or pigmented films, structured or unstructured, are used. Alternatively, the carrier film can be structured on the outside. For example, the carrier film comprises a layer of optically transparent material. The optically opaque material has been applied to this layer in a structured manner, e.g., using a black coating, black paint, black adhesive, a black mold, or another non-reflective material. This structure can be considered a structured layer of optically opaque material. The sections that remain free of optically opaque material form the optically transparent windows (OTW). Alternatively, the OTW can consist of cutouts in the carrier film (CFL).
[0049] An integrated photodetector circuit (IPC) and an integrated driver circuit (IDC) are mounted on and attached to the carbon fiber film (CFL). Both the IPC and IDC are electrically connected to the wiring using contact bumps (BMP). This provides an electrical connection between the circuits and also, for example, via the interface, to an external component. For instance, during operation, the IDC controls the microfluidic cartridge and / or the IPC. Alternatively, the electrical connection between the wiring on the CFL and the IPC and IDC can be established using anisotropic conductive tape or paste / adhesive.
[0050] The integrated photodetector circuit (IPC) is implemented as an ASIC with one or more photodetectors (PDEs) integrated into a single circuit. The number of photodetectors corresponds to the number of measurements that can be performed in parallel. Typically, the photodetectors are photodiodes, such as single-photon avalanche photodiodes, which ensure highly sensitive (photon-counting) detection.
[0051] In the drawing, the photodetectors PDE are depicted as depletion areas of SPADs. These areas are arranged as active surfaces facing the microfluidic cartridge, opposite each detection chamber DEC on the carrier film CFL. The integrated photodetector circuit IPC, and thus the active surfaces, are protected by a passivation layer PAL of the CMOS, which is applied to both the integrated photodetector circuit and the driver circuit. Furthermore, bumps are arranged on surface SF1, which faces the microfluidic cartridge, to enable electrical contact between the integrated photodetector circuit and the wiring WIR. Additionally, a spacer structure SST, comprising, for example, a mold or adhesive, is arranged on surface SF1.This spacer structure positions the flexible film at a distance from the SF1 surface of both the integrated photodetector circuit (IPC) and the driver circuit (IDC). Simultaneously, the spacer structure (SST) protects and seals a detection cavity (CVT). The spacer structure also adheres to the carrier film (CFL), thereby securing the integrated photodetector circuit (IPC) and the driver circuit (IDC) to the flexible film. Finally, the spacer structure (SST) can be designed to act as an optical barrier, minimizing optical crosstalk between the different DEC-PDE pairs / sets. For example, the detection cavities (CVT) within the spacer structure (SST) can be arranged so that the photodetectors (PDE) are enclosed by the structure. This reduces optical crosstalk between the photodetectors.Preferably, the spacer structure is made of opaque materials.
[0052] The microfluidic cartridge comprises one or more detection chambers (DECs) arranged within a cartridge body (CAB). The cartridge body can be made of glass or plastic, or of a transparent or opaque material, or a combination of both. The microfluidic cartridge may contain a single detection chamber (single channel) to allow for sequential measurements, or multiple detection chambers (multiple channels) to enable multiple measurements to be performed in parallel. In the latter case, the cartridge body (CAB) is made of opaque materials to reduce optical crosstalk.
[0053] The microfluidic cartridge further comprises a number of microchannels (MCH), which are also arranged within a cartridge body. The microchannels are connected to the detection chambers to introduce the fluid to be tested. For example, a dedicated microchannel can be provided for each detection chamber to supply the fluid to be tested individually. Alternatively, several detection chambers can share a common microchannel, so that they are all supplied with the same fluid to be tested. Or, the microchannel can lead to the same chamber for waste fluid.
[0054] The microfluidic cartridge is arranged on the CFL support film such that the photodetectors (PDE) are aligned with the optically transparent windows (OTW). For example, the CFL support film rests on the spacer structure (SST). In fact, the CFL support film is only connected to the spacer structure (SST) via its optically opaque sections, while the optically transparent sections remain open. In this way, the detection cavities are aligned with the optically transparent windows (OTW) and the detection chambers (DEC) of the microfluidic cartridge. Simultaneously, each photodetector (PDE) is aligned with its respective detection chamber (DEC) by the integrated photodetector circuit (IPC).
[0055] The flexible foil serves two functions simultaneously. First, it provides electrical wiring structures for establishing electrical contact between the integrated photodetector circuit (IPC) and the integrated driver circuit (IDC). Second, the microfluidic cartridge—that is, the detection chambers (DEC) and / or microchannels (MCH)—is sealed from the environment by the flexible foil, rather than with an additional sealing film. This prevents the photodetectors from coming into direct contact with the liquid being tested. Furthermore, no extra space is required, as no sealing film is needed. This ensures a shorter distance between the detection chamber and the photodetector. As a result of the 1 / R 2 -Depending on the signal-to-noise ratio, it can be improved.
[0056] Optionally, the flexible foil can utilize the WIR wiring (or additional wiring) to heat the detection chambers. In this way, the wiring can act as a heating element. Other heating elements, such as thermocouples, may also be integrated into the flexible foil. These heating elements can be positioned within the flexible foil to be in thermal contact with a single detection chamber (DEC) (one channel) or with multiple detection chambers (multiple channels). As a result of this thermal contact, the heating element can conduct heat to one or more of the detection chambers and thus alter the temperature of any liquid under test that may be present within them.In this way, the liquid in a detection chamber can be heated to a desired temperature, or such a temperature can be kept constant for the duration of one or more successive measurements to establish a reference condition. For example, the liquid can be set to room temperature, or to 37 °C to simulate body temperature. The heating element can be electrically connected to the integrated circuit and / or to a driver circuit.
[0057] In other embodiments, the flexible film can simply comprise a single layer of either optically transparent or optically opaque material. The structuring can be achieved internally or externally, as explained above. However, if the flexible film comprises a single layer of optically opaque material, cutouts can structure the film into sections to form the optically transparent windows. For example, the cutouts can define cavities oriented towards the photodetectors and detection chambers.
[0058] Fig. Figure 2 shows another embodiment of a microfluidic arrangement. This embodiment is the one described in Figure 2. Fig. The above is similar to the one shown. Some aspects are highlighted below, while others are not discussed in detail but may still be present.
[0059] In this embodiment, the microfluidic cartridge comprises multiple detection chambers or, as shown, a single detection chamber and one or more channels. A heating element HEL is arranged in a flexible film. For example, the heating element comprises a heating coil. The flexible film is arranged on the microfluidic cartridge, i.e., on a surface of the cartridge body (not shown). Furthermore, the flexible film is attached to the integrated photodetector circuit and driver circuit by an anisotropic conductive tape ACT. The film is optically transparent or may include a number of cutouts CUT, which are aligned with the photodetectors PDE. The integrated photodetector circuit IPC and the driver circuit IDC are mounted on a substrate CAR, which may be a polyimide laminate or a printed circuit board.This layer can also be replaced by a metallic heat sink to dissipate heat from the integrated circuits.
[0060] The flexible film can consist of a single layer of optically opaque material with cutouts to form the OTW windows. For example, the cutouts can define cavities that are aligned with the photodetectors and detection chambers.
[0061] However, flexible film can also be double-sided with different functionalities. For example, a heating element, such as wiring or a coil, is located on one side for heating (or embedded within it). On the other side, the wiring for electrical contact with the integrated circuits is located (or embedded within it). Despite this dual functionality, flexible film still saves on film thickness, for example, compared to an additional sealing film.
[0062] Fig. Figure 3 shows another embodiment of a microfluidic arrangement. This embodiment is similar to the one described in the Fig. 1 and Fig. The two depicted examples are similar. Some aspects are highlighted below, while others are not discussed in detail but may still be present.
[0063] This embodiment can be considered a combination of those described above with reference to the Fig. 1 and Fig. 2 were discussed. An additional thickness and an assembly step can be saved by using an anisotropic conductive tape (ACT) instead of a spacer structure (SST). The flexible film can be sufficiently opaque or black outside the windows (OTW) to eliminate crosstalk (e.g., printed with dispensing or screen printing, or based on a photopic film). Optionally, the film can be double-sided or bilayered to incorporate a heating element. The integrated photodetector circuit (IPC) and driver circuit (IDC) can optionally be mounted on a substrate (CAR), which can be a polyimide laminate or a printed circuit board. This layer can also be replaced by a metallic heat sink to dissipate heat from the integrated circuits.
[0064] The use of a substrate also facilitates the use of a cooling element. The cooling element can optionally be in thermal contact with the integrated photodetector circuit (IPC). For example, the cooling element can be mounted directly beneath the IPC or a substrate. One option is to implement the cooling element using a Peltier element, with its cooling side facing the IPC. In a lateral dimension, the Peltier element is similar in size to the IPC. Thus, a small Peltier element can be sufficient to cool all the photodetectors in the IPC. A heat sink further facilitates efficient heat transfer to and from the IPC. The heat sinks can be implemented, for example, as vias within the substrate.
[0065] Fig. Figure 4 shows an example of a microfluidic cartridge with a shutter film. The drawing above illustrates the microfluidic cartridge, i.e., not in its assembled state, as shown in Figure 4. Fig. Figure 1 shows the microfluidic cartridge sealed with a sealing film. The sealing film can be flexible foil or a textured sealing film. The drawing below shows the microfluidic cartridge with the sealing film in a top view (from below, as seen from the integrated photodetector circuit). It shows the optically transparent windows (OTW), which are either cutouts in the carrier film (CFL) or sections of optically transparent material. The detection chambers (not shown) are located beneath the optically transparent windows (OTW).
[0066] Fig. Figure 5 shows an example of a structured shutter film. The film comprises a single layer with a structure of sections of optically transparent and optically opaque material. The film consists of a layer of optically transparent material and can be structured from the outside, for example, on one side, both sides, or by injecting pigments or carbon. A photopic material can also be used to achieve the same anisotropy in optical density laterally in the film as perpendicular to the film.
[0067] Fig. Figure 6 shows another example of a structured shutter film. The film comprises a layer LOT of optically transparent material and a layer LOO of optically opaque material, stacked on top of each other. Alternatively, the LOO layer can also be made, for example, on one side, of black paint or adhesives.
[0068] Fig. Figure 7 shows another example of a structured shutter film. The film comprises a layer LOT of optically transparent material and two layers LOO of optically opaque material, stacked on top of each other. Alternatively, the LOO layer can also be made of black paint or adhesives, for example, on both sides.
[0069] The in the Fig. The films shown in the 4 to 7 diagrams can be structured with black and clear sections. For example, the film is produced using a thin-film forming process or a doping process with black carbon. The film can be structured on the outside, e.g., on one side, both sides, or with black paint or adhesive.
[0070] The Fig. 8A and Fig. Figure 8B shows exemplary embodiments of a microfluidic arrangement, which is also referred to below as a microfluidic measuring device. The device comprises a microfluidic cartridge, as explained in the preceding figures. Furthermore, the device comprises a reader RED, which has an opening for inserting the microfluidic cartridge into a measuring position.
[0071] The microfluidic measuring device can be implemented to perform either fluorescence-based or chemiluminescence-based measurements. For the former, the reader can be equipped with an excitation light source to illuminate one or more detection chambers and / or a processing unit to control the light source. This allows the photodetectors to register fluorescence reflected from the liquid in the detection chambers. In such a case, the photodetectors are equipped with the necessary optical filter arrangement to block the excitation light wavelength and detect the fluorescence wavelength.
[0072] Chemiluminescence is the emission of light (luminescence) as a result of a chemical reaction. For this second type of measurement, the reader does not necessarily need to be equipped with a light source, as excitation may not be required to trigger luminescence. However, the microfluidic cartridge, i.e., microchannels, can be used to introduce chemical compounds to trigger chemical reactions, such as test fluids like urine, saliva, blood, or derivatives thereof, which elicit and produce a chemiluminescent response. This can be controlled and / or processed by the processing unit. The reader can be equipped to perform one or both of the above-described types of measurements. The reader can be equipped with a USB interface ( Fig. 8A), or with an interface for a wireless network such as Bluetooth ( Fig. 8B).
[0073] The microfluidic cartridge can be used with a flexible film that seals the cartridge and connects the integrated circuits.
[0074] In this context, further aspects concern the integration of an optical detection chip and a microfluidic cartridge containing light-emitting chemicals. Particularly at low signal strengths, such as for photon counting, as used in most sensitive biodiagnostic reactions, close-range integration is important, since light intensities with 1 / R 2 decrease, where R is the distance between the microfluidic (= sample) and the detector.
[0075] Solutions include a package sensor chip manufactured using FAM (Film Assisted Molding) interfaced with the microfluidic cartridge, or a sensor chip bonded to a flexible film interfaced with the microfluidic cartridge, or chips containing TSV (Through-Silicon Vias) interfaced with the microfluidic cartridge. A microfluidic cartridge can be positioned above a mounting hole of the sensor ASIC, within the mounting hole of the sensor ASIC, or in such a way that the fluid is in direct contact with the sensor ASIC.
[0076] Electrical wiring and heating elements can be integrated within the flexible film, integrated circuits, and / or a substrate. Integration of a cooling element (Peltier element, MEMS cooler) is optional. A single flexible film can be used to electrically wire and connect integrated (detector) circuits and to seal the wells of the microfluidic cartridge.
[0077] The proposed concept enables simpler assembly, including single-channel and multi-channel detection with only one ASIC placement (low assembly cost, high yield, fewer alignment problems), reduced crosstalk between channels, a reduced distance between sample and detector resulting in increased sensitivity, fewer assembly steps, a light-tight arrangement enabling photon counting detection, an integrated heat sink and / or cooler, and with flexible film: integrated electrical wiring for ASIC, an integrated heater, and cartridge sealing. Reference designations ACT anisotropic conductive tape BMP contact bump CAB cartridge body CAR carrier CFL carrier film CUT section CVT detection cavity DEC detection chamber IDC integrated driver circuit IPC integrated photodetector circuit HSK heat sinks LOO layer made of optically opaque material LOT layer of optically transparent material MCH microchannel OTW optically transparent window PAL passivation layer PDE photodetector RED reader SF1 area WIR electrical wiring
Claims
[1] Flexible film for sealing a microfluidic cartridge comprising a flexible carrier film (CFL) and an integrated photodetector circuit (IPC) comprising at least one photodetector (PDE), wherein: - the carrier film (CFL) includes at least one optically transparent window (OTW), - the integrated photodetector circuit (IPC) on the carrier film (CFL) is arranged such that the photodetector (PDE) is aligned with the optically transparent window (OTW), and - the integrated photodetector circuit (IPC) is electrically and functionally connected to the flexible carrier film. [2] Flex film according to claim 1, wherein: - the carrier film (CFL) comprises an array of optically transparent windows (OTW), - the integrated photodetector circuit (IPC) comprises an array of photodetectors, and - the integrated photodetector circuit (IPC) is arranged on the carrier film (CFL) such that each photodetector (PDE) is aligned to a respective optically transparent window (OTW). [3] Flex film according to claim 1 or 2, wherein: - the carrier film (CFL) comprises optically transparent and optically opaque material, and - the carrier film (CFL) is structured such that sections of the carrier film (CFL) comprising the optically transparent material form one or more optically transparent windows (OTW), and / or that sections of the carrier film have cutouts. [4] Flex film according to claim 3, wherein: - the carrier film (CFL) comprises at least one layer (LOT) of optically transparent material and at least one layer (LOO) of optically opaque material, and - the carrier film (CFL) is structured such that sections of the layers (LOT, LOO) form one or more optically transparent windows (OTW). [5] Flex film according to any one of claims 1 to 4, which further comprises an integrated driver circuit (IDC), wherein: - the integrated driver circuit (IDC) is arranged on the carrier film (CFL), and - the integrated driver circuit (IDC) is electrically and functionally connected to the flexible carrier film (CFL). [6] Flex film according to any one of claims 1 to 5, which further comprises electrical wiring (WIR) and an interface (INT), wherein the wiring (WIR) is operable to establish an electrical connection to the integrated photodetector circuit (IPC) and / or the integrated driver circuit (IDC) via the interface (INT). [7] Flex film according to any one of claims 1 to 6, wherein: - the carrier film (CFL) comprises one or more adhesive joints (GJO) to establish contact between the carrier film (CFL) and the integrated photodetector circuit (IPC) and / or the integrated driver circuit (IDC), - the carrier film (CFL) comprises one or more structured spacer structures (SST) to establish contact between the carrier film (CFL) and the integrated photodetector circuit (IPC) and / or the integrated driver circuit (IDC) and / or to block optical crosstalk between the photodetectors (PDE), or - the integrated photodetector circuit (IPC) and / or the integrated driver circuit (IDC) are embedded in the carrier film (CFL). [8] Flex film according to any one of claims 1 to 7, wherein the carrier film (CFL) has a thickness between 10 and 200 µm. [9] Microfluidic arrangement comprising: - a microfluidic cartridge comprising a cartridge body (CAB) having at least one detection chamber (DEC) connected to a microchannel (MCH) to receive a fluid to be tested, - a flexible film according to any one of claims 1 to 8, which is attached to the microfluidic cartridge in order to seal the at least one detection chamber (DEC) and / or the associated microchannel (MCH), and wherein: - the microfluidic cartridge on the flexible film is arranged such that one or more of the photodetectors (PDE) of the integrated photodetector circuit (IPC) are aligned to a respective detection chamber (DEC). [10] Microfluidic arrangement according to claim 9, which further comprises a reader, wherein the reader comprises an opening for inserting the microfluidic cartridge into a measuring position to perform a fluorescence and / or chemiluminescence measurement. [11] Microfluidic arrangement according to claim 9 or 10, wherein the cartridge body (CAB) comprises multiple detection chambers (DEC) which are connected to a respective microchannel (MCH) to accommodate one or more liquids to be tested. [12] Microfluidic arrangement according to any one of claims 9 to 11, wherein the cartridge body (CAB) comprises an optically opaque and / or non-reflective material. [13] Microfluidic arrangement according to any one of claims 9 to 12, wherein: - the detection chambers (DEC) and / or microchannels (MCH) in the cartridge body (CAB) are designed as open cavities and / or - the detection chambers (DEC) and / or microchannels (MCH) are sealed by means of a flexible film arranged on the cartridge body (CAB).
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