EP4263057A1

EP4263057A1 - Adaptation of a processing of an in particular biological sample using a processing unit

Info

Publication number: EP4263057A1
Application number: EP21835266.4A
Authority: EP
Inventors: Martin Schulz; Jochen Rupp
Original assignee: Robert Bosch GmbH
Current assignee: Robert Bosch GmbH
Priority date: 2020-12-16
Filing date: 2021-12-10
Publication date: 2023-10-25
Also published as: WO2022128768A1; DE102020215986A1; CN116887918A

Abstract

The invention relates to a method (600) for adapting a processing of an in particular biological sample using a processing unit (700) and to a correspondingly configured processing unit (700). The invention also relates to a label (100) having an identification region (110, 120, 130, 140) for a processing parameter for adapting a processing and to a cartridge (500) having such a label (100).

Description

description

title

Adaptation of a processing of a particularly biological sample with a processing unit

State of the art

So-called lab-on-a-chip systems (LoC systems for short) are microfluidic systems that accommodate the functionalities of a macroscopic laboratory on a plastic substrate for a process that is as fully automated as possible.

These systems often include both a cartridge into which a sample to be analyzed is placed and an analyzer into which the cartridge is placed to carry out the analysis. While the analysis device typically has all active technical means such as heaters, hydraulic or pneumatic controls for the cartridge, the cartridge, which is usually designed as a disposable product, has no active components but is equipped with the necessary biochemical reagents and is inexpensive.

For example, the documents DE 10 2016 222 075 A1 and DE 10 2016 222 072 A1 each describe a microfluidic system with a cartridge for receiving a biological sample and a processing unit for processing the sample in the cartridge. The processing unit can be set up to carry out different processing methods depending on the type of analysis desired. For this purpose, the processing unit usually has one or more interfaces for the required data input, for example a touch-sensitive display, a camera and/or a wireless communication interface such as Bluetooth, WLAN or NFC. Disclosure of Invention

Advantages of the Invention

Against this background, the invention relates to a method for adapting a processing of a sample with a processing unit. For this purpose, a cartridge is identified in an identification area for a processing parameter and the processing parameter is read in by the processing unit. If the reading is successful, the intended processing of the sample in the cartridge is adjusted depending on the processing parameters. Processing can then be carried out by the processing unit.

The sample can in particular include a biological sample, for example a body fluid such as blood, urine, sputum or a smear or tissue from an animal or a human.

The processing unit can be understood in particular as a microfluidic processing unit or analysis unit for processing and/or analysis of the sample received in the cartridge, which is based, for example, on a processing unit described in DE 10 2016 222 075 A1 or DE 10 2016 222 072 A1. Processing unit and cartridge can together form a microfluidic system, in particular a lab-on-a-chip system. In this case, the processing unit is set up to adapt the processing as a function of the recorded processing parameter. The subject matter of the invention is therefore also such a processing unit. The processing unit preferably has a communication interface for reading in, in particular an optical interface such as a camera or a reading device for reading in bar codes or two-dimensional codes.

A cartridge can be understood in particular as a microfluidic cartridge, based for example on a cartridge described in DE 10 2016 222 075 A1 or DE 10 2016 222 072 A1. Such cartridges are often designed as passive components and are of the Processing unit operated for processing the sample contained in the cartridge. The cartridge has the identification area for the processing parameter and is therefore also the subject of the invention. The subject matter of the invention is also a microfluidic system comprising such a cartridge and the processing unit described above.

Processing by the processing unit can be understood to mean processing of the cartridge and the sample in the cartridge, in particular microfluidic processing, for example a biochemical method for detecting substances or pathogens.

A processing parameter can be understood in particular as information which, after processing by the processing unit, influences the processing of the cartridge. Such processing typically includes controlling a fluidic process in the cartridge for processing the sample, for example controlling valves and actuators for transporting the sample and/or mixing the sample with other substances in the cartridge and/or controlling temperature controls for Setting a local temperature in the cartridge, for example to carry out a polymerase chain reaction. The information encoded by the processing parameter can preferably bring about an adaptation of individual or multiple processing steps of the processing, in particular a specification or change of a part of the fluidic sequence.

An identification area for a processing parameter can be understood in particular as a predetermined area on the cartridge in which the identification takes place when the cartridge is used as intended. The identification area can be a marked area on a surface of the cartridge, for example a bordered area or a marked area. The identification area preferably already contains a first piece of information about the processing parameter. In this case, the identification can preferably be done by supplementing the first information, for example by marking (e.g. highlighting or ticking) or by adding further information, for example manual addition or printing or sticking with the further information. The first piece of information can thus also be referred to as “identifiable information”.

In a preferred embodiment, the processing unit can carry out a number of different processing operations, for example independent or parallel analyzes of samples for different pathogens (different viruses and/or bacteria and/or other pathogens). In other words, the processing unit is preferably set up to carry out a number of different processing methods. At least one of the processings or one of the processing methods can be adjusted by the processing parameter and thus modified. An adaptation of the processing can thus preferably not be understood as a mere selection of one of a plurality of processing methods, but rather an adaptation of one or more steps of one or more specific processing methods.

The method presented thus enables flexible processing of the cartridge and thus in particular increased universality of known microfluidic, (partially) automated processing methods, with the respective parameterization of the processing advantageously being able to take place automatically by reading in the processing parameters. In addition, with the method presented, the processing parameters are provided directly by the marked cartridge, which advantageously increases the security for correct processing, in particular for a correct assignment of cartridge and processing.

The processing parameter can include information on the desired analysis of the sample, for example a determination of the entities to be determined, for example the pathogens to be detected, or a determination of termination criteria for the processing and thus preferably a determination of the desired quality of the processing. In advantageous configurations of the invention, the cartridge can also be marked with several processing parameters. The processing can advantageously be automated by reading in the one or more processing parameters be adjusted. This reduces the effort and the susceptibility to errors due to otherwise manual input by the user.

The processing parameter particularly preferably includes information on the type of sample. A medium is often added to fluidic samples, in particular body fluids or tissue, in particular a medium for stabilizing and/or preserving and/or preparing the sample, also referred to as sample medium. A preparation of the sample can be understood as meaning a reaction, in particular a chemical or biochemical reaction and thus a change in the sample. For example, the medium can be, among other things, a preservation or transport medium such as eNAT™ or UMT™ or the cotton wool of a cotton swab (also called a “swab”). The processing parameter can thus include information about the medium, so that the processing of the sample is preferably adapted depending on the sample medium. In particular, as explained above, one or more steps of a specific processing method can be adapted depending on the type of sample, for example a way of cleaning the sample. In the context of the invention, the term “sample type” can be equated with the totality of sample and sample medium, since the medium typically has a decisive influence on the type of sample.

The coding of the information on the type of sample by the processing parameter thus has the advantage that by adapting the processing to the type of sample and in particular to the type of medium, a more reliable, more efficient and more effective sample processing with a higher probability of success and/or higher yield can take place. In particular, this enables processing that is tailored to the type of sample. A further advantage is that the processing unit can thus be used for a number of different sample types. In addition, as already explained in general above, the presented method provides information about the sample type directly through the marked cartridge, which advantageously increases the security for correct processing, correct sample input into the cartridge and correct assignment of sample type and processing. According to a preferred development of the method, the user is prompted to enter the processing parameter via a communication interface of the processing unit if the reading in of the processing parameter is not successful. This request and also the input can be made, for example, via a touch-sensitive display of the processing unit. Reading in is not successful in particular if the information read in cannot be processed, for example because the information is unknown to the processing unit or is defective. A processing unit set up in this way has the advantage that the processing cannot be aborted but can be continued via interaction with the user.

The identification of the cartridge can preferably include a label (also called “label”), the label having an identification area for the processing parameter, in particular an identification area as described above. The subject matter of the invention is therefore also such a label and a cartridge with such a label.

The proposed label advantageously enables a clear and physically permanent assignment of the cartridge and the processing parameter, in particular the sample type of the sample to be or has already been taken up in the cartridge. Such a label can be applied to a surface of the cartridge without difficulty, which enables the user and/or the processing unit to read in the processing parameters marked on it in an uncomplicated manner. For this purpose, the label can have an at least partially adhesive underside.

In a preferred embodiment, the label, in particular the identification area, includes information about a processing parameter that can be identified. As described above, the item of information that can be identified is to be understood as meaning first information about the processing parameter, which is supplemented with further information by a user and thus identified. As described above, the additional information can be supplemented, for example, by ticking or marking the first information or by adding further information formulated in plain text or in code. The first piece of information has the advantage that the user is already made aware of the processing parameter in question and can select or determine or also specify the processing parameter in a simple manner through the identification or supplementation.

According to a particularly preferred embodiment, the label comprises a first identification area for a first type of sample and a second identification area for a second type of sample. These two different areas have the advantage that it is easy to distinguish between the two types of samples. The different areas can in particular be two areas on the upper side of the label which only partially overlap locally or preferably not at all. In addition, the label can have additional identification areas for additional, in particular other types of samples, for example a third area or a third and fourth area, with the areas overlapping only partially or preferably not at all locally.

In a particularly advantageous embodiment, at least one identification area includes a number of identification fields. At least one identification area preferably has a first identification field and a second identification field. In this case, the first identification field can be provided for an identification of a specific type of sample. The first identification field preferably includes the sample type in plain text, for example the word “eNAT” or “UTM” or “Swab” and preferably corresponds to the information that can be identified as described above. The second identification field can be provided for a selection of the sample type specified in the first identification field. The selection can preferably be made by entering information (in particular the “further information” described above) in the second identification field, for example by writing, in particular by manually ticking or manually filling in the second identification field by the user. Alternatively, the Entry can also be made by sticking another label in the second identification field. Thus, in this refinement, the identification of the second identification field advantageously indicates which type of sample is present.

The identification fields are preferably different areas on the label which only partially overlap locally or preferably not at all. This has the advantage of a low risk that another identification field will be impaired or damaged by marking one identification field, in particular by manual identification in the form of filling out, ticking or sticking on another label.

Furthermore, at least one identification area can have a third identification field. The third identification field can be provided for entering a sample identifier, the sample identifier preferably uniquely identifying a sample, as also described above. Alternatively, independently of the identification area and the third identification field, the label can have a sample identification area for a sample identifier. A sample identifier is to be understood in particular as a clear assignment or identification of the sample, in particular in relation to the sampling and/or to the person from whom the sample was taken. This advantageously facilitates tracking of the sample located in the cartridge. For example, the sample identifier can be in the form of a code, in particular in the form of a numeric code, a bar code or a two-dimensional code such as a QR code. The sample identifier can be applied to a sample label, for example, with the sample label being applied to the third identification field. By entering the sample identifier, the selection of the sample type is advantageously recorded on the one hand and the information on the sample is physically permanently linked to the cartridge and the type of sample on the other hand. The second identification field and the third identification field can also be designed as a common second identification field, so that the common second identification field, as explained above, can be filled out either manually or with another label, in particular the sample label mentioned above.

At least one identification area can include a code, the code encoding information, in particular a processing parameter such as an identifier for the type of sample or an identifier for the sample. For example, the code is a bar code, a data matrix code, or a QR code. The first identification area preferably includes such a code for coding the type of sample, preferably in addition to plain text on the type of sample. This has the advantage that both a human user and the processing unit can directly record the type of sample present. If, as stated above, one or more identification areas have one or more identification fields, one or more of the identification fields can in particular include such a code.

In a preferred embodiment of the invention, the cartridge includes a cartridge identifier. The cartridge identifier can preferably include a unique designation of the cartridge or a unique designation of a type of cartridge, in particular in the form of a code. The cartridge identifier can preferably be applied to a surface of the cartridge.

According to an advantageous development, the label has a cartridge identification area for the cartridge identification of the cartridge. This has the advantage that both the processing parameters, in particular the type of sample, and the identification of the cartridge are physically permanently connected via the label. Furthermore, applying the label to the cartridge ensures a permanent connection to the cartridge.

Brief description of the drawings

Embodiments of the invention are shown schematically in the drawings and explained in more detail in the following description. For the elements shown in the various figures and acting similarly the same reference symbols are used, with a repeated description of the elements being dispensed with.

Show it

Figures la, lb exemplary embodiments of the label according to the invention,

FIG. 2 exemplary embodiments of the system according to the invention, including exemplary embodiments of the cartridge according to the invention and the processing unit according to the invention, and

FIG. 3 shows a flowchart of an exemplary embodiment of the method according to the invention.

Embodiments of the invention

Figures la and lb show an embodiment of the label 100 according to the invention. For example, as shown, the label 100 has a basically rectangular shape with optionally rounded corners and an exemplary size of 6 centimeters by centimeters cm. The label 100 is designed to be placed on a surface of a microfluidic cartridge to be applied, for example via an adhesive underside of the label 100. In this example, the processing parameter is the sample type.

In this example, the label 100 has a first identification area 110, which is delimited by a rectangular border. The first identification area includes four identification fields 111, 112, 113, 114, which are separated from one another by further lines. The first identification field 111 contains a pre-printed human-readable sample type name ("eNAT"). The second identification field 112 is intended for manual ticking by the user, as shown in FIG. As an alternative to ticking, a sample identifier can be entered in the third identification field 113, for example in the form of a bar code (as shown), for example by sticking another label in the third identification field 113. The third identification field indicates this For example, a size of 25 millimeters by 10 millimeters, which corresponds to a typical size of labels for samples in the laboratory area. In this example, the fourth identification area 114 includes a QR code that encodes the sample type (here “eNAT”) for optical reading by a processing unit. Due to the local separation of the identification fields 111, 112, 113, 114, the visibility of the first identification field 111 and also the fourth identification field 114 and the respective sample type listed therein is not impaired when the second identification field 112 is ticked or when the third identification field is filled in. In this example, the entry in the first identification field 111 ("eNAT") and/or the QR code in the fourth identification field 114 represent the information that can be identified as described above, which can be obtained by ticking the second identification field 112 and/or the entries in the third identification field 113 marked and so that the process parameter (here the sample type) eNAT is selected.

In the exemplary embodiment shown, the label 100 comprises four locally separate identification areas 110, 120, 130, 140, with all four areas 110, 120, 130, 140 preferably having the four identification fields described. Each labeling area 110, 120, 130, 140 represents a different sample type, as shown in the respective first labeling field 111, 121, 131, 141, in this example the first labeling field 141 of the fourth labeling area 140 being left blank for the user to fill in. By ticking one of the second identification fields, as shown in second identification field 112 in Figure 1b, or by filling in one of the third identification fields, in particular by sticking on a sample identification label 113 as shown in Figure la, the processing parameter is thus identified as to which sample type is provided. In other embodiments, the label 100 can have a different number of identification areas and also a different number of identification fields, it being possible for the number of identification areas to depend in particular on the number of possible different sample types. The label 100 also has a cartridge identifier 150 in a cartridge identifier area 160 next to the identifier areas 110, 120, 130, 140 as a possible further processing parameter, the cartridge identifier 150 being implemented as a QR code in this example. The label 100 thus represents a physical connection between the cartridge identifier, the sample type identifier and optionally the sample identifier.

Figure 2 shows an exemplary embodiment of a microfluidic system 1000 comprising exemplary embodiments of a processing unit 700 according to the invention and a cartridge 500 according to the invention.

The cartridge 500 includes a sample chamber 510 for receiving the biological sample which is to be processed with the aid of the cartridge 500 and the processing unit 700 . The sample chamber 510 can be closed with a cover 520 of the sample chamber 510 before the cartridge 500 is inserted into a shaft 760 of the processing unit 700 for the processing.

In this example, the label 100 has already been applied to the cartridge 500 and can be read in via the processing unit 700 . For this purpose, the processing unit 700 includes an optical sensor 710, for example a camera or a barcode scanner. The processing unit 700 also includes a wireless communication interface 730 for exchanging data, for example based on Bluetooth®, WLAN or NFC, and an interaction surface 740, for example a touch-sensitive display surface, also known as a “touch screen”, for entering and displaying information. The processing unit 700 also has means (not shown) for processing the cartridge 500 . These means can be mechanical, pneumatic or thermal actuators typical in microfluidics for carrying out microfluidic processes in the cartridge, such as plungers, heating elements or compressed air connections.

A processor 720 of the processing unit 700 is set up, one or more processing parameters such as the identifier of the sample type, the cartridge identifier and optionally the sample identifier via the optical sensor 710 to read in and to adapt and carry out processing of the cartridge 500 depending on the type of sample.

FIG. 3 shows a flow chart of an exemplary embodiment of the method 600 according to the invention, which can be carried out, for example, with a microfluidic system 1000 described above.

In a first step 601 a sample is taken, for example a biological sample from a human or an animal, for example a body fluid such as blood or sputum or a swab. The sample is brought into contact with a medium for preservation and/or transport or already during sampling, for example with a liquid medium such as eNAT™ or UTM™ or with a cotton swab (“swab”). Before or after this, in a second step, a sample identifier is created for the clear identification of the sample, in particular in the form of a clear code, for example a number and/or a bar code.

In a second step 602, a cartridge 500 suitable for the sample and the desired type of processing is provided and identified with one or more processing parameters in one or more identification areas. In this example, by ticking one of the second identification fields or by filling out one of the third identification fields, in particular by sticking on a sample identification label 113 (as shown in Figure la) or by ticking the second identification field 112 (as shown in Figure lb), thus defined as a processing parameter which sample type and thus which sample medium is present.

In a third step 603, the processing parameters are read in via the optical sensor 710 of the processing unit 700 and the processing is adapted, in this case the microfluidic processes are defined to match the sample medium present and thus the sample type present. The reading of the processing parameter preferably includes the optical reading of a large part or preferably the entire label 100. Very preferably, at least all of the labels present on the label 100 are used Identification areas 110, 120, 130, 140 read. For this purpose, the processing unit 700 can be set up to recognize the identification areas 110, 120, 130, 140, for example via the boundary lines shown on the label and/or the QR codes in the fourth identification fields. The specified sample type is then determined by the processor 720 of the processing unit via an identification of one of the identification areas 110, 120, 130, 140 in the second or third identification fields. The identified identification area 110, in particular the identified second or third identification field, determines which type of sample is present, this type of sample being identified by the plain text entry in the first identification area 111 and/or the coded entry in the fourth identification area 114. In the exemplary embodiment according to FIG. In the exemplary embodiment according to FIG. adjusted by the processor 720. For example, the way the sample is cleaned is adapted for the most effective and efficient possible extraction of the essential sample components from the eNAT medium. This is done, for example, by adjusting the duration and intensity of ultrasonic lysis parameters, adjusting the volume of lysis, binding or washing buffers and process parameters such as incubation times, temperatures and sequential or parallel fluidic processes.

In another embodiment, a dry sample, such as a swab, may be labeled "Swab." The course of the associated processing is thus adapted for processing a sample with the sample medium “swab” by the processor 720. Here, an increased volume is used to rinse out the dry swab in the processing.

The adjustment of the processing can also be the adjustment of processing steps such as in particular a selection of evaluation paths for measured test results and cartridge data as well as a Include how results are presented. For example, defining a curve scaling for a sample type can be advantageous.

If the read-in information on the processing parameter cannot be processed by the processing unit 700, in one

Intermediate step 603a via a communication interface, in particular via the display 740, a request to the user to enter the processing parameter manually. This can happen, for example, if the marking 602 on the cartridge is incorrect or illegible.

In a fourth step 604, the sample is processed by the processing unit after the processing in the cartridge 500 has been successfully adjusted.

Claims

Expectations

1. Method (600) for adapting a processing of an in particular biological sample with a processing unit (700), comprising the steps:

• Identification (602) of a cartridge (500), wherein the identification takes place in an identification area (110, 120, 130, 140) for a processing parameter.

• Reading in (603) the processing parameters from the marked cartridge (500) by the processing unit (700) and adapting the processing depending on the processing parameters

• Processing (604) of the sample in the cartridge (500) by the processing unit (700)

2. The method (600) according to claim 1, wherein the identification of the cartridge (500) comprises a label (100), the label (100) having the identification area (110, 120, 130, 140) for the processing parameter.

3. The method (600) according to claim 1 or 2, wherein the processing is adapted with respect to a sample type of the sample.

4. The method (600) according to any one of the preceding claims, wherein the user is prompted to enter the processing parameter via a communication interface (740) if the reading in of the processing parameter is not successful.

5. Label (100) for an in particular microfluidic cartridge, the label (100) having an identification area (110, 120, 130, 140) for a processing parameter for adapting a processing of the cartridge (500) having.

6. Label (100) according to claim 5, wherein the label (100), in particular the identification area (110, 120, 130, 140), comprises information about a processing parameter that can be identified.

7. Label (100) according to claim 5 or 6, wherein the processing parameter comprises information about a sample type.

The label (100) of claim 7, wherein the label (100) comprises a first identification area (110) for a first sample type and a second identification area (120) for a second sample type.

9. Label (100) according to any one of claims 5 to 8, wherein at least one identification area (110, 120, 130, 140), in particular an identification field (111, 112, 113, 114), comprises a code, the code containing information encoded, in particular information on the processing parameters.

10. Label (100) according to one of claims 5 to 9, wherein the label (100) has a sample identification area (113) for a sample identifier and/or a cartridge identification area (156) for a cartridge identifier (100) of the cartridge (500).

11. Cartridge (500), in particular microfluidic cartridge (500), wherein the cartridge (500) has an identification area (110, 120, 130, 140) for a processing parameter for adapting a processing of the cartridge (500).

12. cartridge (500) with a label (100) according to any one of the preceding claims

13. Cartridge (500) according to claim 11 or 12, wherein the cartridge (500) comprises a cartridge identifier (150), in particular wherein the cartridge identifier (150) is applied to a surface of the cartridge (500), preferably on the label - 18 -

(100).

14. Processing unit (700) for processing an in particular microfluidic cartridge (500), wherein the processing unit (700) is set up to adapt the processing with respect to a processing parameter read in by the processing unit (700).

15. Microfluidic system (1000) comprising a processing unit (700) according to claim 14 and a cartridge (500) according to one of claims 11 to 13.