Cartridge for an analytical device for processing a sample contained in the cartridge, method and device for processing a sample contained in a cartridge using an analytical device and analytical device

The cartridge for an analysis device addresses the challenge of thermal energy management in lab-on-a-chip systems by using a thermally conductive spring arm and elastic membrane for efficient thermal contacting, enabling fast PCR cycling and improved analysis efficiency.

DE102023213244A1Pending Publication Date: 2025-06-26ROBERT BOSCH GMBH
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Patent Information

Application Number
DE102023213244
Authority / Receiving Office
DE · DE
Patent Type
Applications
Current Assignee / Owner
Filing Date
2023-12-22
Publication Date
2025-06-26

AI Technical Summary

Technical Problem

Existing lab-on-a-chip systems for PCR analysis face challenges in efficiently introducing and managing thermal energy for rapid cycling, which can lead to increased costs and reduced analysis speed.

Method used

The proposed cartridge for an analysis device incorporates a carrier substrate with deflection chambers and an elastic membrane for pneumatic sealing, along with a switchable cycling element featuring a thermally conductive spring arm that can be thermally contacted with a temperature control unit, allowing for efficient thermal energy management.

Benefits of technology

This solution enables fast PCR cycling by geometrically separated switchable thermal contacting, reducing thermal resistance and allowing for rapid heating and cooling rates, thereby enhancing the efficiency and speed of PCR analysis.

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Abstract

The invention relates to a cartridge (105) for an analysis device (100) for processing a sample contained in the cartridge (105), wherein the cartridge (105) comprises a carrier substrate (200) with at least one deflection chamber (205), an elastic membrane (210) at least partially integrated into the carrier substrate (200) for pneumatically sealing the deflection chamber (205), and a switchable cycling element (215) arranged on the carrier substrate (200) with a thermally conductive spring arm (220), wherein the spring arm (220) has a contact section (225) at a free end, which is designed for thermal contact with a temperature control unit (125) of the analysis device (100) using a pressing force generated by a deflected membrane (210), wherein the contact section (225) is arranged opposite the at least one deflection chamber (205). is.
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Description

State of the art

[0001] The invention relates to a cartridge for an analytical device for processing a sample contained in the cartridge, a method and a device for processing a sample contained in a cartridge using an analytical device, and an analytical device according to the preamble of the independent claims. The present invention also relates to a computer program.

[0002] Lab-on-a-Chip (LoC) systems are microfluidic systems that automatically accommodate the entire functionality of a macroscopic laboratory on a plastic substrate. Samples for analysis, such as human swabs, are typically transferred into liquid transport media. The cell material, bacteria, virus particles, or body fluids are transferred into the transport medium, washed out, and then subjected to molecular diagnostic analysis using a polymerase chain reaction (PCR). This allows pathogens, antibiotic resistance, or other characteristics to be genetically determined. Disclosure of the invention

[0003] Against this background, the approach presented here provides an improved cartridge for an analytical device for processing a sample contained in the cartridge, an improved method for processing a sample contained in a cartridge using an analytical device, an improved device using this method, and finally, a corresponding computer program and an improved analytical device according to the main claims. The measures listed in the dependent claims enable advantageous refinements and improvements of the device specified in the independent claim.

[0004] The presented approach can create an advantageous way to quickly transfer thermal energy into and out of a cycling element. Among other things, the choice of material and the shape of the cycling element can be advantageous for thermal conductivity. Furthermore, manufacturing costs can be reduced.

[0005] A cartridge for an analytical device for processing a sample contained in the cartridge is presented, wherein the cartridge comprises a carrier substrate with at least one deflection chamber, an elastic membrane, preferably at least partially integrated into the carrier substrate, for pneumatically sealing the deflection chamber, and a switchable cycling element with a thermally conductive spring arm, preferably arranged on the carrier substrate. The spring arm has a contact section at a free end, which is designed for thermally contacting a temperature control unit of the analytical device using a pressure force generated by a deflected membrane. The contact section is further arranged opposite the at least one deflection chamber.

[0006] The cartridge can advantageously be designed as a lab-on-chip cartridge so that tests can be carried out quickly. Such cartridges can be used, for example, for PCR tests. For example, the cartridge can have the cycling element in which corresponding samples can be processed or cycled, i.e., treated in one or more processing cycles. The carrier substrate can, for example, have silicon as its base material. The at least one deflection chamber can, for example, be designed as a recess in the carrier substrate. The membrane can also be at least partially arranged in the cartridge, preferably between two layers of the cartridge, in particular the carrier substrate, in such a way that it is deflected when the deflection chamber is pneumatically acted upon, for example with compressed air, and the pressing force can thereby be generated.The spring arm can, for example, be designed as a resilient spring element whose contact section can be pressed onto the temperature control unit at its free end. The contact section can therefore advantageously be designed as a thermal contact or have such a contact. The temperature control unit can advantageously have at least one heating element and additionally or alternatively at least one cooling element or be designed as such. The actual deflection of the spring arm can advantageously be achieved by force transmission through the elastic membrane arranged in the cartridge. Mechanical or pneumatic deflection can be advantageous in order to be able to deflect the contact section in the direction of the heating elements. Decoupling can be achieved via the restoring force of the spring arm.The force required for good thermal contact between the spring arm and the heating element can therefore be adjusted via the geometry of the deflected elastic membrane. The deflection via the membrane eliminates the need for fixed mechanical plungers or similar devices in the analyzer, thus resulting in very good thermal decoupling.

[0007] According to one embodiment, the spring arm and the contact section can be made of one piece and additionally or alternatively made of metal. This can advantageously improve the stability of the cycling element, thus reducing the susceptibility to errors in analysis results. Advantageously, the cycling element and thus also the spring arm and additionally or alternatively the contact section can comprise silicon, thus improving thermal conductivity. The mechanical properties of silicon for spring arms can advantageously be very well adjusted via the geometry of the spring arms, thus achieving a high level of functional reliability during operation.

[0008] Furthermore, the spring arm can be designed with a bent design. This advantageously allows the cyclinder element to be used for different cartridge types or sizes or analysis ranges.

[0009] According to one embodiment, the spring arm in the contact section can be at least partially planar, stepped, and additionally or alternatively T-shaped. Additionally or alternatively, the contact section can have a raised portion extending away from the deflection chamber. The raised portion can advantageously be round, triangular, or square. Other shapes can also be realized. Furthermore, the shape of the contact section can advantageously reduce thermal resistance.

[0010] Furthermore, the carrier substrate can have at least one further deflection chamber, wherein the membrane can be designed to pneumatically seal the further deflection chamber. The cycling element can have at least one further thermally conductive spring arm, wherein the further spring arm can have a further contact section at a free end, which is designed for thermal contact with a temperature control unit using the further pressing force generated by the deflected membrane. The further contact section can be arranged opposite the at least one further deflection chamber. The deflection chamber and the further deflection chamber can advantageously be of the same design and, for example, have a round outline. The chambers can be integrated into the carrier substrate offset from one another, for example diagonally with respect to a surface of the carrier substrate.The temperature control unit can advantageously generate different temperatures in the different deflection chambers.

[0011] According to one embodiment, the cycling element can have a body, wherein the spring arm and the further spring arm can be arranged on the same side of the body, offset from one another. Additionally or alternatively, the spring arm and the further spring arm can be arranged on two adjacent sides of the body. The body of the cycling element can advantageously be polygonal, in particular quadrangular. This means that the body can have a first side, a second side adjacent to the first side, a third side opposite the first side and adjacent to the second side, and a fourth side connecting the first and third sides. The sides can, for example, be of the same length or different lengths, so that the body can be realized as rectangular or square.The two spring arms can, for example, be arranged parallel or at least approximately parallel to each other, so that the cycling element can have a comb-like shape. The cycling element can advantageously have additional spring arms in addition to the two spring arms, so that the cycling element and thus the cartridge can be used for a variety of analyses.

[0012] Furthermore, the cycling element can be made of a silicon-containing material. This material selection advantageously allows for faster heating and cooling rates, eliminating the need for Peltier elements, for example, and thus reducing costs. Overall, silicon exhibits advantageous thermal and, additionally or alternatively, mechanical properties.

[0013] The cartridge can further comprise at least one additional switchable cycling element arranged on the carrier substrate with a thermally conductive additional spring arm, wherein the additional spring arm can have an additional contact section at a free end, which is designed to thermally contact the temperature control unit using an additional pressing force generated by the deflected membrane. The additional contact section can be arranged opposite the at least one deflection chamber and additionally or alternatively an additional deflection chamber of the carrier substrate. The cycling elements can be shaped identically so that they can be arranged on the carrier substrate in a space-saving manner. Advantageously, both cycling elements can contact the at least one temperature control unit of the analysis device through the same deflection chambers.

[0014] Furthermore, a method for processing a sample contained in a cartridge in a previously mentioned variant using an analysis device is presented, wherein the method comprises a step of deflecting the membrane in the deflection chamber in order to exert a pressing force on the contact section, and a step of transferring the spring arm into a contact position using the pressing force, wherein the contact section of the spring arm is pressed onto a temperature control unit of the analysis device in the contact position in order to establish a thermal connection.

[0015] The method can advantageously be carried out in an analysis device. Advantageously, the membrane can be mechanically or pneumatically loaded during the deflection step, allowing it to deform and, as a result of this deformation, press against the spring arm. The steps of the method can advantageously be performed repeatedly. This method can be implemented, for example, in software or hardware, or in a hybrid form of software and hardware, for example, in a control unit.

[0016] According to one embodiment, the method may include a step of holding the thermal contact in the contact position for a predefined period of time and / or a step of controlling the temperature control unit to control the temperature of the contact section. Advantageously, an achievable temperature may be dependent on the period of time. The control may also bring the contact section to a desired temperature, which is then passed, for example, to the cycling unit.

[0017] The approach presented here further provides a device configured to perform, control, or implement the steps of a variant of a method presented here in corresponding devices. This embodiment of the invention in the form of a device also allows the problem underlying the invention to be solved quickly and efficiently.

[0018] For this purpose, the device can have at least one computing unit for processing signals or data, at least one memory unit for storing signals or data, at least one interface to a sensor or an actuator for reading sensor signals from the sensor or for outputting data or control signals to the actuator, and / or at least one communication interface for reading or outputting data embedded in a communication protocol. The computing unit can be, for example, a signal processor, a microcontroller, or the like, wherein the memory unit can be a flash memory or a magnetic storage unit.The communication interface can be designed to read in or output data wirelessly and / or wired, wherein a communication interface that can read in or output wired data can read this data, for example, electrically or optically from a corresponding data transmission line or output it to a corresponding data transmission line.

[0019] In this case, a device can be understood as an electrical device that processes sensor signals and outputs control and / or data signals depending on them. The device can have an interface that can be implemented in hardware and / or software. In a hardware implementation, the interfaces can, for example, be part of a so-called system ASIC, which contains various functions of the device. However, it is also possible for the interfaces to be separate integrated circuits or to consist at least partially of discrete components. In a software implementation, the interfaces can be software modules that are present, for example, on a microcontroller alongside other software modules.

[0020] Also advantageous is a computer program product or computer program with program code that can be stored on a machine-readable carrier or storage medium such as a semiconductor memory, a hard disk memory or an optical memory and is used to carry out, implement and / or control the steps of the method according to one of the embodiments described above, in particular when the program product or program is executed on a computer or a device.

[0021] There is also provided an analysis device for processing a sample contained in a cartridge in a previously mentioned variant, wherein the analysis device has an aforementioned device, a receiving area for receiving the cartridge and a temperature control unit which is designed to temperature control the contact section when the spring arm of the cartridge is pressed onto the temperature control unit in the contact position.

[0022] The analyzer can advantageously be used in the medical field, for example, to analyze PCR tests. The cartridge can be designed, for example, as a lab-on-chip cartridge. The temperature control unit can advantageously be designed as a heating unit or cooling unit.

[0023] According to one embodiment, the temperature control unit can comprise at least one temperature control element configured as a heating element and / or a cooling element. In particular, the temperature control unit can be configured to generate temperatures between 90 degrees to 110 degrees, 50 degrees to 70 degrees, and additionally or alternatively 70 degrees to 75 degrees. This means that advantageously, a temperature range can be assigned to each of several heating elements or cooling elements.

[0024] Examples of the approach presented here are shown in the drawings and explained in more detail in the following description. It shows: Fig. 1 a schematic representation of an embodiment of an analysis device; Fig. 2 a schematic sectional view of an embodiment of a cartridge; Fig. 3 a schematic representation of an embodiment of a cartridge; Fig. 4 a schematic sectional view of an embodiment of a cartridge; Fig. 5 a schematic sectional view of an embodiment of a cartridge; Fig. 6 a schematic sectional view of an embodiment of a cartridge; Fig. 7 a schematic sectional view of an embodiment of a cartridge; Fig. 8 a schematic representation of an embodiment of a cartridge; Fig. 9 a schematic representation of an embodiment of two cycling elements for a cartridge; Fig. 10 is a schematic representation of an embodiment of two cycling elements for a cartridge; Fig. 11 is a schematic side view of an embodiment of a cyclizing element for a cartridge; Fig. 12 is a schematic side view of an embodiment of a cyclizing element for a cartridge; Fig. 13 is a schematic side view of an embodiment of a cyclizing element for a cartridge; Fig. 14 is a schematic side view of an embodiment of a cyclizing element for a cartridge; Fig. 15 is a flowchart of an embodiment of a method for processing a sample contained in a cartridge using an analytical device; and Fig. 16 a block diagram of a device according to an embodiment.

[0025] In the following description of advantageous embodiments of the present invention, the same or similar reference numerals are used for the elements shown in the various figures and having a similar effect, whereby a repeated description of these elements is omitted.

[0026] Fig. 1 shows a schematic representation of an embodiment of an analysis device 100. In this embodiment, the analysis device 100 is designed to analyze input samples, allowing, for example, PCR tests to be performed. For this purpose, a cartridge 105, for example, with a plastic housing and a microfluidic network for processing the sample, can be inserted into a receiving area 110 of the analysis device 100. Only optionally, the analysis device 100 further comprises a display 115 with a touch function for manually entering settings for the desired analysis process, merely by way of example. Furthermore, the display 115 is designed merely by way of example to display analysis results.

[0027] Accordingly, the analysis device 100 is designed to process a sample contained in the cartridge 105 and, in addition to the receiving area 110, has a device 120 that is designed to control and / or carry out a method for processing the sample, as described in more detail in at least one of the following figures. The device 120 is designed, for example, as a control unit or as a control device. Furthermore, the analysis device 100 has a temperature control unit 125. The temperature control unit 125 is designed, for example, as at least one heating unit or a cooling unit, or has such units that are designed to temperature-control a contact section within the cartridge 105 when a spring arm of the cartridge 105 is pressed onto the temperature control unit 125 in a contact position. The cartridge 105 is described in more detail in the following figures.

[0028] In other words, the approach and the analyzer 100 achieve rapid PCR cycling through geometrically separated, switchable thermal contact. Real-time or endpoint PCR is typically performed cyclically using a two- or three-step thermal process. Multiple PCR reactions in parallel, so-called multiplex PCR, within one analyzer 100 has the advantage that many properties can be identified from a patient sample simultaneously. This minimizes the complexity of the individual PCR reaction and thus makes it more robust. Other known geometric multiplex methods, such as microarray analysis, require an additional time-consuming analysis step after the PCR. Geometric multiplexing of multiple parallel PCR detections is advantageous when the PCR cycling speed is correspondingly high.

[0029] Against this background, a possibility for fast PCR cycling is created by a geometrically separated switchable thermal contact, as described below.

[0030] Fig. 2 shows a schematic sectional view of an embodiment of a cartridge 105 as shown in Fig. 1 has already been mentioned. According to this embodiment, an initial state of the cartridge 105 is shown. The cartridge 105 has a carrier substrate 200 with at least one deflection chamber 205 and an elastic membrane 210 at least partially integrated into the carrier substrate 200 for pneumatically sealing the deflection chamber 205. As an alternative to the integration of the membrane 210 in the carrier substrate 200, the membrane 210 can also be arranged differently, provided that it pneumatically seals the deflection chamber 205, for example between a further substrate layer of the cartridge 105 and the carrier substrate 200 and / or partially glued to the carrier substrate 200 or welded to the carrier substrate. For example, the two in Fig. 2 and spaced apart by the membrane 210 can also be designed as two separate layers of the cartridge 105, which are connected in particular via regions of the membrane 210. The carrier substrate 200 is designed, for example, as a silicon wafer. Furthermore, the cartridge 105 has a switchable cycling element 215 arranged on the carrier substrate 200 with a resilient, thermally conductive spring arm 220, wherein the spring arm 220 has a contact section 225 at a free end, which is designed for thermally contacting a temperature control unit 125 of the analysis device using a pressing force generated by a deflected membrane 210. The contact section 225 is arranged opposite the at least one deflection chamber 205. For example, the spring arm 220 and the contact section 225 is or are designed as a single piece and / or made of metal and is or can be designed to be bent only optionally.Furthermore, the cycling element 215 comprises, for example, a silicon-containing material. According to this exemplary embodiment, the cycling element 215 is positively connected to the carrier substrate 200. Alternatively, the cycling element 215 need not be arranged directly on the carrier substrate, but rather merely needs to be arranged relative to the carrier substrate, in particular adjacent to it, in such a way that the contact section 225 can be touched by the membrane 210 upon deflection of the membrane 210 into the deflection chamber 205, thereby deflecting the spring arm 220.

[0031] According to this exemplary embodiment, the carrier substrate 200 has at least one further deflection chamber 230, wherein the membrane 210 is designed to pneumatically seal the further deflection chamber 230. The cycling element 215 has at least one further thermally conductive spring arm, which is described in more detail, for example, in at least one of the following figures. The further spring arm has, for example, at a free end, a further contact section 235, which is designed for thermal contact with a temperature control unit 125 using the further pressing force generated by the deflected membrane 210. The further contact section 235 is further arranged opposite the at least one further deflection chamber 230. Furthermore, the carrier substrate 200 additionally has a third deflection chamber 240, which is designed similarly to the deflection chamber 205 and / or the further deflection chamber 230.According to this exemplary embodiment, the cycling element 215 further comprises a third thermally conductive spring arm. The third spring arm has, for example, a third contact section 245 at a free end, which is designed to thermally contact a temperature control unit 125 using the third contact force generated by the deflected membrane 210. The third contact section 245 is also arranged opposite the third deflection chamber 240.

[0032] According to this exemplary embodiment, the temperature control unit 125 accordingly has three temperature control elements 250, 255, 260, which are designed, for example, as heating elements. Alternatively, the temperature control elements 250, 255, 260 can be designed as cooling elements.

[0033] In other words, an integrated thermal contacting mechanism within a cartridge 105 is described. The mechanism is that a limitation of a maximum heating and cooling rate for an integrated miniaturized PCR cycling element 215, in particular a silicon-based miniaturized microtiter plate, in a cartridge 105 is lifted by the thermal inertia of the analyzer's external heating and cooling elements. In the design and process described here, isothermally operated temperature control elements 250, 255, 260, also referred to as heating or cooling elements, of the temperature control unit 125 are used, and only the cycling element 215 is heated and cooled.

[0034] The mechanism is designed such that thermal contact is established between the cycling element 215 and an associated stationary heating or cooling element of the temperature control unit 125 via the deflectable membrane 210. The temperature control elements 250, 255, 260, also referred to as heating or cooling elements, are independent of one another and geometrically separated. The cycling element 215 has thermal contacts, also referred to as contact sections 225, 235, 245, which extend geometrically far enough to lie above the corresponding heating or cooling element 250, 255, 260. In the initial state, all thermal contacts 225, 235, 245 of the cycling component 215 are without contact with the temperature control unit 125. The temperature control elements 250, 255, 260 each have a target temperature, for example.

[0035] In summary, Fig. 2 shows a sketched side view of a multi-layer structure with integrated cycling element 215 and deflectable spring arms for thermal contact with heating or cooling elements 250, 255, 260. Typical temperatures for the initial state are, for example, 90°C to 110°C for the temperature control element 250, 50°C to 70°C for the temperature control element 255 and 70°C to 75°C for the temperature control element 260 compared to a room temperature or internal device temperature.

[0036] Fig. 3 shows a schematic representation of an embodiment of a cartridge 105, as it is used, for example, at least in Fig. 2. According to this exemplary embodiment, the cartridge 105 is shown in plan view so that one shape of the cycling element 215 is visible. According to this exemplary embodiment, the cycling element 215 has three spring arms 220, 300, 305, which are arranged parallel to one another on a body 310 of the cycling element 215 and are thus shaped like a comb. At least two of the spring arms 220, 300, 305 are arranged offset from one another, for example, on the same side 315 of the body 310. The spring arms 220, 300, 305 have different lengths. Additionally or alternatively, at least two of the spring arms 220, 300, 305 can be arranged on two adjacent sides 315, 320 of the body 310. For example, the cyclinder element 215 is square and therefore has four sides 315, 320, 325, 330.It has a first side 315, a second side 320 adjacent to the first side 315, a third side 325 opposite the first side 315 and adjacent to the second side 320, and a fourth side 330 connecting the first side 315 and the third side 325.

[0037] According to this exemplary embodiment, the temperature control unit 125 also has the three temperature control elements 250, 255, 260, whose main extension direction runs transversely to a main extension direction of the carrier substrate 200 and the cycling element 215. The deflection chambers 205, 230, 240, which only optionally have a round outline, are each arranged above one of the temperature control elements 250, 255, 260, so that the spring arms 220, 300, 305 can contact the temperature control elements at the level of the deflection chambers 205, 230, 240. For example, the spring arm 220 is assigned to the deflection chamber 205 and the temperature control element 250. The additional spring arm 300, which is longer than the spring arm 220, is assigned to the deflection chamber 230 and the tempering element 255. The third spring arm 305, according to this embodiment, is assigned to the deflection chamber 240 and the tempering element 260.

[0038] The following described Fig. 4 to 7 each show a snapshot of an exemplary sequence for a thermal cycle in a cartridge 105. First, a first contact section 225, also referred to as a thermal contact element, of the cycling component 215 is pressed onto a temperature control element 250. The thermal energy flows via the contact into the cycling element 215 and brings it to the temperature of the heater 250. A holding time dependent on the PCR reaction is waited for. To set the next temperature, the first thermal contact element 225 is mechanically separated from the first heating element 250, and a thermal contact element 245 is pressed onto a heating element 260. This sets a second temperature on the cycling element 215 for the PCR. A holding time dependent on the PCR reaction is waited for.To set the next temperature, the thermal contact element 245 is mechanically separated from the heating element 260, and a thermal contact element 235 is pressed onto a heating element 255. This sets a third temperature on the cycling element 215 for the PCR. Here, too, a holding time dependent on the PCR reaction is waited. To set the next temperature, the thermal contact element 235 is mechanically separated from the heating element 255. The cycle is then repeated until a certain number of cycles have been completed.

[0039] Here, only three temperatures and corresponding holding times are described as examples. However, fewer or more different temperatures and holding times may also be useful.

[0040] For example, in a classic PCR, the number of steps is as described above, with these steps being performed up to 50 times, typically 40 consecutively. Typical hold times are 0 to 60 seconds.

[0041] In a simple PCR, the number of steps is two, which are repeated up to 50 times, typically 40 consecutively. Typical hold times are 0 to 60 seconds.

[0042] In a so-called isothermal amplification, the number of steps is 1, and usually only the duration is adjusted. A typical duration is between 2 and 30 minutes.

[0043] Fig. 4 shows a schematic sectional view of an embodiment of a cartridge 105, as used, for example, in at least one of the Fig. 1 to 3 or at least mentioned. According to this exemplary embodiment, a first snapshot of the previously described exemplary sequence for a thermal cycle is shown. A first contact section 225 of the cycling component 215, also referred to as a thermal contact element, is pressed onto a temperature control element 250. The thermal energy flows via the contact into the cycling element 215 and brings it to the temperature of the heater 250. A holding time dependent on the PCR reaction is waited for.

[0044] Here, too, the cartridge 105 comprises the carrier substrate 200, the membrane 210, and the cycling element 215. According to this exemplary embodiment, the deflection chamber 205 is pneumatically pressurized, so that the membrane 210 in the deflection chamber 205 exerts the pressing force 400 on the contact section 225, which is symbolically represented according to this exemplary embodiment. Using the pressing force 400, the spring arm 220 is deformed, so that the contact section 225 contacts the temperature control unit 125, in particular the temperature control element 250, and, for example, heat is conducted to the body 310 of the cycling element 215. The heat flow 405 is symbolically represented according to this exemplary embodiment.

[0045] Fig. 5 shows a schematic sectional view of an embodiment of a cartridge 105, which, for example, corresponds to the one shown in Fig. 4. According to this exemplary embodiment, the third deflection chamber 240 is pneumatically actuated instead of the deflection chamber 205. This means that the membrane 210 deflects in the third deflection chamber 240 and thereby exerts a third pressing force 500 on the third contact section 245, thus pressing it onto the tempering element 260.

[0046] In other words, according to this exemplary embodiment, a second snapshot of the previously described exemplary sequence for a thermal cycle is shown. To set the next temperature, the first thermal contact element 225 is mechanically separated from the first heating element 250, and a thermal contact element 245 is pressed onto a heating element 260. This sets a second temperature on the cycling element 215 for the PCR. A holding time dependent on the PCR reaction is waited for. According to this exemplary embodiment, a heat outflow 505 from the body 310 to the third deflection chamber 240 is symbolically shown.

[0047] Fig. 6 shows a schematic sectional view of an embodiment of a cartridge 105, which, for example, corresponds to the cartridge shown in at least one of the Fig. 4 to 5. According to this exemplary embodiment, the membrane 210 is deflected in the further deflection chamber 230 in order to exert the further pressing force 600 on the further contact section 235 and press it onto the further tempering element 255. As a result, the heat generated by the further tempering element 255 is conducted to the cycling element 215. The heat flow 405 is represented symbolically according to this exemplary embodiment.

[0048] In other words, according to this exemplary embodiment, a third snapshot of the previously described exemplary sequence for a thermal cycle is shown. To set the next temperature, the thermal contact element 245 is mechanically separated from the heating element 260, and a thermal contact element 235 is pressed onto a heating element 255. This sets a third temperature on the cycling element 215 for the PCR. Here, too, a holding time dependent on the PCR reaction is waited for.

[0049] Fig. 7 shows a schematic sectional view of an embodiment of a cartridge 105, which, for example, corresponds to the one shown in Fig. 4. Here, too, the membrane 210 presses the contact section 225 onto the temperature control element 250. According to this embodiment, the deflection chamber 205 is again pneumatically pressurized, so that the membrane 210 in the deflection chamber 205 again exerts the pressing force 400 on the contact section 225, which is symbolically represented according to this embodiment. Using the pressing force 400, the spring arm 220 is deformed, so that the contact section 225 again contacts the temperature control unit 125, in particular the temperature control element 250, and, for example, heat is conducted to the body 310 of the cycling element 215. The heat flow 405 is symbolically represented according to this embodiment and corresponds, for example, to the Fig. 4 described heat flow.

[0050] In other words, to set the next temperature using the temperature control element 250, the thermal contact element 235 is mechanically separated from the heating element 255. The cycle is then repeated until a certain number of cycles have been completed.

[0051] Fig. Figure 8 shows a schematic representation of an embodiment of a cartridge 105, which, for example, corresponds to the cartridge shown in at least one of the Fig. 1 to 7. According to this exemplary embodiment, at least two of the spring arms 220, 300, 305 are arranged on the same side 315 of the body 310 of the cycling element 215, and two of the spring arms 220, 300, 305 are arranged on the two adjacent sides 315, 320. More precisely, the spring arm 220 is arranged on the second side 320, and the spring arms 300, 305 are arranged on the first side 315 of the body 310. Furthermore, according to this exemplary embodiment, the spring arms 300, 305 are bent. The spring arm 220 is at least partially planar according to this exemplary embodiment. Additionally or alternatively, the spring arm 220, or also the other spring arms 300, 305, is designed in a stepped and / or T-shaped manner and / or has a raised portion extending from the at least one deflection chamber 205, 230, 240, as is shown, for example, in at least one of the Fig. 13 to 14.

[0052] Fig. 9 shows a schematic representation of an embodiment of two cyclizing elements 215, 900 for a cartridge, as used, for example, in at least one of the Fig. 1 to 8. According to this embodiment, the cycling element 215 corresponds to that described in at least one of the Fig. 2 to 7. This means that the cartridge has, for example, at least one additional cycling element 900, which, like the cycling element 215, is arranged on the carrier substrate and is also switchable. The additional cycling element 900 has at least one thermally conductive additional spring arm 905, wherein the additional spring arm 905 has an additional contact section 910 at a free end, which is designed to thermally contact the temperature control unit and / or an additional temperature control unit of the analysis device using an additional pressing force generated by the deflected membrane. Furthermore, the additional contact section 910 is arranged opposite the at least one deflection chamber and / or an additional deflection chamber of the carrier substrate.

[0053] According to this exemplary embodiment, the cycling element 900 and the additional cycling element 900 are designed similarly, so that the additional cycling element 900, like the previously described cycling element 215, has three spring arms 905, 915, 920 arranged parallel to one another. According to this exemplary embodiment, the spring arm 905 lies on the same plane as the spring arm 220, the spring arm 915 lies on the same plane as the further spring arm 300, and the spring arm 920 lies on the same plane as the third spring arm 305. This further means that the contact section 225 and the contact section 910 lie on a common plane. Furthermore, the contact section 235 and a contact section 922 of the spring arm 915 lie on a common plane, and the contact section 245 lies on a common plane with a contact section 924 of the spring arm 920.

[0054] Since the spring arms 220, 300, 305, 900, 915, 920 of the individual cyclizing elements 215, 900 are of different lengths and are of the same design, the cyclizing elements 215, 900 can be inserted into the carrier substrate in a space-saving manner. According to this exemplary embodiment, the cyclizing elements 215, 900 are arranged rotated 180° relative to one another with respect to a main extension axis 925.

[0055] Fig. 10 shows a schematic representation of an embodiment of two cyclizing elements 215, 900 for a cartridge, as used, for example, in at least one of the Fig. 1 to 8. According to this embodiment, the cycling element 215 is similar to that described in at least one of the Fig. 2 to 8. As in Fig. 9, according to this embodiment, two similar cyclinder elements 125, 900 are shown, but rotated by 180° with respect to the main extension axis 925. According to this embodiment, the spring arm 220, in particular each of the spring arms 220, 300, 305, 900, 915, 920, is at least partially planar, stepped and / or T-shaped in its corresponding contact section 225, 235, 245, 910, 922, 924 and / or has a raised portion extending away from the deflection chamber, as is shown, for example, in at least one of the Fig. 13 to 14. More specifically, according to this embodiment, the contact sections 235, 922 are T-shaped and the other contact sections 225, 245, 910, 924 are square.

[0056] Fig. 11 shows a schematic side view of an embodiment of a cyclizing element 215 for a cartridge. The cyclizing element 215 shown here corresponds to or at least resembles the one shown in one of the Fig. 1 to 10 mentioned cyclinder element. In Fig. 11, the features of the cyclizing element 215 with respect to the spring arm 220 are described, wherein the features can also be transferred to other spring arms of the cyclizing element 215.

[0057] According to this exemplary embodiment, the cycling element 215 comprises the body 310 and the spring arm 220. The contact section 225 is arranged at a free end of the spring arm 220. According to this exemplary embodiment, the body 310 has a surface 1100 and a further surface 1105 opposite the surface 1100, with the spring arm 220 adjacent to the further surface 1105. This means that the spring arm 220 and the further surface 1105 lie on a common plane. Overall, the spring arm 220 and the contact section 225 are planar.

[0058] Fig. 12 shows a schematic side view of an embodiment of a cyclizing element 215 for a cartridge, which, for example, corresponds to the one shown in Fig. 11 described cyclizing element. Only one position of the spring arm 220 differs according to this embodiment from Fig. 11. More precisely, the spring arm 220 is arranged on the surface 1100.

[0059] Fig. 13 shows a schematic side view of an embodiment of a cyclizing element 215 for a cartridge, which, for example, corresponds to the one shown in Fig. 12 described cyclin element. In addition, the Fig. The cycling element 215 shown in Figure 13 has a protrusion 1300 in the contact section 225 that is triangular in cross-section. The protrusion 1300 extends away from the deflection chamber when installed.

[0060] Fig. 14 shows a schematic side view of an embodiment of a cyclizing element 215 for a cartridge, which, for example, corresponds to the one shown in at least one of the Fig. 12 to 13. According to this embodiment, the cycling element 215 is at least partially planar and / or stepped in the contact section 225.

[0061] Fig. 15 shows a flow diagram of an embodiment of a method 1500 for processing a sample contained in a cartridge using an analytical device, such as that described in Fig. 1. Consequently, the method 1500 is carried out using a cartridge as described, or at least parts of the cartridge, for example, in at least one of the Fig. 2 to 14 was or were described.

[0062] The method 1500 comprises a deflection step 1505 and a transfer step 1510. In the deflection step 1505, which occurs mechanically or pneumatically, for example, the membrane is deflected in the deflection chamber to exert a pressing force on the contact section. This means that the membrane presses against the contact section of the spring arm. In the transfer step 1510, the spring arm is transferred into a contact position using the pressing force, wherein the contact section of the spring arm is pressed in the contact position onto a temperature control unit of the analysis device to establish a thermal connection. Furthermore, the method 1500 optionally only comprises a step 1515 of holding the thermal contact in the contact position for a predefined period of time. For example, steps 1505, 1510, and 1515 of the method 1500 can be performed repeatedly.

[0063] In other words, the method 1500 enables rapid PCR cycling through geometrically separated switchable thermal contacting.

[0064] Fig. 16 shows a block diagram of a device 120 according to an embodiment, as shown for example in Fig. 1 as part of the analysis device. The device 120 is designed to control and / or carry out a method for processing a sample contained in the cartridge, as described in Fig.15. For this purpose, the device comprises a deflection unit 1605, a transfer unit 1610, and optionally a holding unit 1615. The deflection unit 1605 is designed, for example, to cause the membrane to deflect in the deflection chamber in order to exert a pressing force on the contact section. The transfer unit 1610 is designed to cause the spring arm to be transferred into a contact position using the pressing force, wherein the contact section of the spring arm is pressed onto a temperature control unit of the analysis device in the contact position in order to establish a thermal connection. The holding unit 1615 is designed to cause the thermal contact to be held in the contact position for a predefined period of time.

[0065] If an embodiment includes an “and / or” link between a first feature and a second feature, this should be read as meaning that the embodiment according to one embodiment includes both the first feature and the second feature and according to another embodiment includes either only the first feature or only the second feature.

Claims

[1] Cartridge (105) for an analysis device (100) for processing a sample contained in the cartridge (105), the cartridge (105) having the following features: - a carrier substrate (200) with at least one deflection chamber (205); - an elastic membrane (210), preferably at least partially integrated into the carrier substrate (200), for pneumatically sealing the deflection chamber (205); and - a switchable cycling element (215), preferably arranged on the carrier substrate (200), having a thermally conductive spring arm (220), wherein the spring arm (220) has a contact section (225) at a free end, which is designed to thermally contact a temperature control unit (125) of the analysis device (100) using a pressing force (400) generated by a deflected membrane (210), wherein the contact section (225) is arranged opposite the at least one deflection chamber (205). [2] Cartridge (105) according to claim 1, wherein the spring arm (220) and the contact portion (225) are formed in one piece and / or are made of metal. [3] Cartridge (105) according to one of the preceding claims, wherein the spring arm (220) is bent. [4] Cartridge (105) according to one of the preceding claims, wherein the spring arm (220) in the contact section (225) is at least partially planar and / or stepped and / or T-shaped and / or has an elevation (1300) extending away from the deflection chamber (205). [5] Cartridge (105) according to one of the preceding claims, wherein the carrier substrate (200) has at least one further deflection chamber (230), wherein the membrane (210) is designed to pneumatically seal the further deflection chamber (230), wherein the cycling element (215) has at least one further thermally conductive spring arm (300), wherein the further spring arm (300) has at a free end a further contact section (235) which is designed to thermally contact a temperature control unit (125) using the further pressing force (600) generated by the deflected membrane (210), wherein the further contact section (235) is arranged opposite the at least one further deflection chamber (230). [6] Cartridge (105) according to claim 5, wherein the cycling element (215) has a body (310), wherein the spring arm (220) and the further spring arm (300) are arranged on the same side of the body (310) offset from one another on the body (310), and / or wherein the spring arm (220) and the further spring arm (300) are arranged on two adjacent sides of the body (310). [7] Cartridge (105) according to one of the preceding claims, wherein the cycling element (215) comprises a silicon-containing material. [8] Cartridge (105) according to one of the preceding claims, with at least one additional switchable cycling element (900) arranged on the carrier substrate (200) with a thermally conductive additional spring arm (905), wherein the additional spring arm (905) has an additional contact section (910) at a free end, which is designed to thermally contact the temperature control unit (125) using an additional pressing force generated by the deflected membrane (210), wherein the additional contact section (910) is arranged opposite the at least one deflection chamber (205) and / or an additional deflection chamber (230, 240) of the carrier substrate (200). [9] A method (1500) for processing a sample contained in a cartridge (105) according to any one of the preceding claims using an analysis device (100), the method (1500) comprising the following steps: - deflecting (1505) the membrane (210) in the deflection chamber (205) to exert a pressing force (400) on the contact section (225); and - transferring (1510) the spring arm (220) into a contact position using the pressing force (400), wherein the contact section (225) of the spring arm (220) in the contact position is pressed onto a temperature control unit (125) of the analysis device (100) in order to establish a thermal connection. [10] Method (1500) according to claim 9, comprising a step (1515) of holding the thermal contact in the contact position for a predefined period of time and / or comprising a step of controlling the temperature control unit (125) for temperature control of the contact section (225). [11] Device (120) which is arranged to carry out and / or control the steps (1505, 1510, 1515) of the method (1500) according to one of claims 9 to 10 in corresponding units (1605, 1610, 1615). [12] Computer program configured to execute and / or control the steps (1505, 1510, 1515) of the method (1500) according to any one of claims 9 to 10. [13] A machine-readable storage medium on which the computer program according to claim 12 is stored. [14] Analysis device (100) for processing a sample contained in a cartridge (105) according to one of claims 1 to 8, wherein the analysis device (100) has the following features: - a device (120) according to claim 11; - a receiving area (110) for receiving the cartridge (105); and - a tempering unit (125) designed to temper the contact section (225) when the spring arm (220) of the cartridge (105) is pressed onto the tempering unit (125) in the contact position. [15] Analysis device (105) according to claim 14, wherein the temperature control unit (125) has at least one temperature control element (250, 255, 260) formed as a heating element and / or a cooling element, in particular wherein the temperature control unit (125) is designed to generate temperatures between 90 degrees to 110 degrees and / or 50 degrees to 70 degrees and / or 70 degrees to 75 degrees.

Citation Information

Patent Citations

  • Thermostat

    DE102015114043A1