DE202022100905U1 - Device for receiving samples - Google Patents

Abstract

Device (1) for receiving biological samples for carrying out a PCR analysis method for determining pathogenic microorganisms, in particular pathogenic viruses, especially viruses that cause respiratory diseases, with a receiving container (2) with a first opening (4), a closure device ( 6), which is adapted to the opening (4) of the receptacle (2), so that the opening (4) of the receptacle (2) can be closed with the closure device (6), the closure device (6) having a through-opening (20) characterized in that the receiving container (2) contains a liquid preparation composition for carrying out a PCR test on site (Point of Care; PoC).

Description

The invention relates to a device for receiving samples for carrying out a PCR analysis method for determining pathogenic microorganisms, in particular pathogenic viruses, especially viruses that cause respiratory diseases. The devices according to the invention are suitable for carrying out on-site PCR methods (Point of Care; PoC-PCR). In addition, the invention relates to the use of the device for a PoC PCR test method and methods for carrying out an on-site PCR method (PoC-PCR).

Pathogenic viruses that cause respiratory diseases often spread rapidly and can lead to a confusing course of infection up to and including pandemic conditions. Recently, the spread of corona viruses, especially SARS CoV-2 viruses, has led to a pandemic with major health and economic damage. An essential part of combating the pandemic is reliable and rapid diagnosis of the presence of pathogenic viruses in order to be able to initiate targeted therapies and measures and thus contain the spread.

The reliable gold standard for the detection of pathogenic viruses, in particular SARS-CoV-2 viruses, are PCR methods, which are usually carried out as standard in special laboratories. The disadvantage, however, is that these PCR tests are time-consuming, can only be carried out by specialist personnel and require purification and transport of the patient samples taken from the sampling site to the laboratory.

There is therefore a great need to carry out tests that are reliable and can be carried out quickly with regard to the determination of pathogenic viruses.
Surprisingly, it was found that PCR tests (PoC; point of care) can be carried out on site using suitable devices for taking samples. It is particularly advantageous that the patient samples taken are expensive to transport and that there is no need for any expensive purification of the samples. The PCR tests can thus be carried out close to the patient and directly on site, for example in test centers, pharmacies or doctor's offices.

For this purpose, the sampling devices must not only be practical and easy to use for on-site use, they must also be equipped and designed in such a way that PCR tests can be carried out directly on site.

This object is solved by the objects according to the independent claims of the present invention. The dependent claims reflect advantageous and preferred embodiments of the present invention.

One subject of the invention is a device for receiving biological samples for carrying out a PCR analysis method for determining pathogenic microorganisms, in particular pathogenic viruses, especially viruses that cause respiratory diseases, with a receiving container with a first opening, a closure device which is attached to the Opening of the receiving container is adapted so that the opening of the receiving container can be closed with the closure device, wherein the closure device has a through opening and wherein the receiving container contains a liquid preparation composition for on-site (Point of Care; PoC) carrying out a PCR test.

In an advantageous embodiment, the device also has a sampling device, which has at least one first sampling element on a first free end, with which the sample can be removed, and wherein the sampling device can be inserted into the receptacle. This configuration has the advantage that the device and the sampling device are present together in one system and the risk of contamination is therefore reduced in practice in use.

The sampling device is preferably connected to the closure device at a second end opposite the first free end, so that the sampling device can be inserted into the receptacle by means of the closure device.

In a further preferred embodiment, the passage opening of the closure device is closed by means of a closure element, the closure element being separably attached to the closure element.

In a further embodiment, the sampling device has at least one hollow rod-shaped element, at the free end of which the sampling element is arranged, the hollow rod-shaped element forming a channel on the inside.

The rod-shaped element can be connected to the closure device in such a way that the channel of the rod-shaped element opens into the through-opening or is arranged in it.

In a preferred embodiment, the passage opening of the closure element is closed on the side opposite the sample-taking element by means of a closure element that is separably fastened to the closure element.

For practical reasons of handling, it is advantageous that the closure element can be separated from the closure element by bending. In principle, however, other alternatives familiar to the person skilled in the art are also possible and can be used. For example, the terminating element can also be separable such that it can be twisted off.

In one embodiment, the hollow rod-shaped element has at least one opening at the free end. It is particularly preferred that the end of the channel arranged in the rod-shaped element forms the opening at the free end. It is further preferred that the opening arranged at the free end is arranged in the wall of the rod-shaped element.

The device, in particular the receiving container, advantageously has an identification code. This enables the patient's information to be quickly and reliably associated with the sample to be analyzed. In particular when carrying out PCR tests on several samples at the same time, this can avoid confusion when carrying out, evaluating and identifying.

The device of the present invention is particularly suitable for on-site testing for corona viruses. The viruses are preferably corona viruses, in particular SARS CoV-2 viruses.

In principle, the devices according to the invention can be used specifically for viruses that cause respiratory diseases. One or more viruses are preferably selected from the group consisting of SARS CoV-2 virus, influenza virus and adenovirus.

PCR tests in the field of virus analysis and detection are known to those skilled in the art. In the context of the present invention, it is advantageous if the PCR test is a quantitative PCR method (qPCR) or a quantitative real-time PCR (RT-qPCR).

The biological samples, particularly for examining viruses that cause respiratory diseases, are preferably saliva and/or nasopharyngeal secretion.

An essential part of the present invention is that the receptacle contains a liquid preparation composition for carrying out a PCR test on site (Point of Care; PoC). The preparation composition ensures that the biological samples can be tested directly on site using a PCR method, without the need for further purification of the sample. The liquid treatment composition preferably comprises guanidinium thiocyanate. The conditioning composition is preferably an aqueous composition. It has been found advantageous to keep the concentration of guanidinium thiocyanate below 1M. This improves the direct use of the biological sample together with the preparation composition in a PCR test.

The liquid treatment composition also preferably has one or more surfactants.

The liquid treatment composition also advantageously has one or more RNAase inhibitors, preferably 2 different RNase inhibitors.

It has proven to be advantageous for the liquid treatment composition to contain a buffer. This is due in particular to the fact that the biological samples, in particular saliva and nasophyngeal secretion, can have a different pH value depending on the patient

The liquid treatment composition preferably contains biotin.

Another subject is the use of the device according to the invention for a PoC PCR test method.

1. a) Bereitstellen einer erfindungsgemäßen Vorrichtung,
2. b) Inkontaktbringen einer biologischen Probe, vorzugsweise Saliva und/oder nasopharyngeales Sekret, mit der flüssigen Aufbereitungszusammensetzung zur vor Ort (Point of Care; PoC) Durchführung eines PCR-Tests,
3. c) Verwenden der flüssigen Aufbereitungszusammensetzung umfassend die biologische Probe in einem PoC-PCR-Verfahren.

Another subject is a method for performing an on-site PCR method (PoC-PCR) comprising the following steps:

1. a) providing a device according to the invention,
2. b) contacting a biological sample, preferably saliva and/or nasopharyngeal secretion, with the liquid treatment composition for on-site (Point of Care; PoC) implementation of a PCR test,
3. c) using the liquid processing composition comprising the biological sample in a PoC-PCR method.

In a preferred embodiment, the liquid treatment composition is incubated together with the biological sample, preferably incubated at 15 to 30° C. and in particular over a period of 1 to 30 minutes, specifically Incubated for 2 to 15 minutes, more preferably 3 to 10 minutes.

In a further embodiment of the method, the preparation composition containing the sample can be mixed with a PCR reaction mixture.

The PCR reaction mixture preferably comprises polymerase and primers and probes for the detection of pathogenic microorganisms, in particular pathogenic viruses, especially viruses causing respiratory diseases.

1. a) Bereitstellen einer erfindungsgemäßen Vorrichtung,
2. b) Inkontaktbringen einer biologischen Probe, vorzugsweise Saliva und/oder nasopharyngeales Sekret, mit der flüssigen Aufbereitungszusammensetzung zur vor Ort (Point of Care; PoC) Durchführung eines PCR-Tests zur Bestimmung von Corona Viren, insbesondere SARS CoV-2 Viren,
3. c) gegebenenfalls Inkubieren der flüssigen Aufbereitungszusammensetzung zusammen mit der biologischen Probe,
4. d) Mischen der flüssigen Aufbereitungszusammensetzung umfassend die biologische Probe mit einer PCR-Reaktionsmischung umfassend Polymerase und Primer und Sonden für den Nachweis von Corona Viren, insbesondere SARS CoV-2 Viren.

In a special embodiment, the method according to the invention comprises the following steps:

1. a) providing a device according to the invention,
2. b) contacting a biological sample, preferably saliva and/or nasopharyngeal secretion, with the liquid preparation composition for carrying out a PCR test on site (point of care; PoC) to determine corona viruses, in particular SARS CoV-2 viruses,
3. c) optionally incubating the liquid treatment composition together with the biological sample,
4. d) Mixing the liquid processing composition comprising the biological sample with a PCR reaction mixture comprising polymerase and primers and probes for the detection of corona viruses, in particular SARS CoV-2 viruses.

The PoC-PCR method is preferably a multiplex PCR method.

The PCR reaction mixture has 2 or more probes for the detection of SARS-CoV-2 viruses, 2 or more primers and polymerase, in particular Taq polymerase, reverse transcriptase and optionally a buffer.

1. a) eine erfindungsgemäße Vorrichtung,
2. b) optional eine Probenentnahmevorrichtung und
3. c) optional ein oder mehrere separate(r) Behälter mit einer oder mehreren PCR Reaktionsmischung(en).

Another item is a kit comprising

1. a) a device according to the invention,
2. b) optionally a sampling device and
3. c) optionally one or more separate containers with one or more PCR reaction mixture(s).

The in 1 until 5 illustrated embodiment explained in more detail. The liquid treatment composition is not shown in the figures. This is located in the receptacle.

The invention advantageously provides that the sample-taking device is connected to the closure device at a second end opposite the first free end, so that the sample-taking device can be inserted into the receptacle by means of the closure device.

This embodiment of the present invention has the advantage that taking the samples is simplified. The sampling device does not first have to be placed elsewhere in order to open the closure device. And on the other hand, the closure device does not have to be placed anywhere so that the sampling device can be inserted into the receptacle.

The sampling device can have at least one hollow rod-shaped element, at the free end of which the sampling element is arranged, the hollow rod-shaped element forming a channel on the inside.

The extraction element can consist of a material which can be absorbent or adhesive in relation to liquids. This means that the removal element can suck up the liquid or the liquid adheres to the removal element.

An absorbent material can be, for example, an element made of cotton wool. Alternatively, it can be any other element capable of absorbing moisture.

The holding tank can be waterproof and airtight.

The closure device can have a through-opening.

The rod-shaped element can be connected to the closure device in such a way that the channel of the rod-shaped element opens into the through-opening or is arranged in it.

The passage opening of the closure element can be closed on the side opposite the sample-taking element by means of a closure element that is separably fastened to the closure element.

After the end element has been separated off, the through opening forms an opening to the outside. With the end element separated, the processing unit located in the receptacle can be settling liquid due to capillary action and / or pressure and / or negative pressure from the channel of the rod-shaped element and the through-opening to the outside.

The closing element can be separated from the closure element by bending. Alternatively, the closing element can also be separable from the closure element by unscrewing.

The hollow rod-shaped element can have at least one opening at the free end.

The end of the channel arranged in the rod-shaped element can form the opening at the free end.

The opening located at the free end may be located in the wall of the rod-shaped element.

• - Bereitstellen eines Aufnahmebehälters mit einer ersten Öffnung,
• - Entnahme einer Probe mit zumindest einem an einem freien Ende einer Probenentnahmeeinrichtung angeordneten Entnahmeelements, wobei
• - die Probenentnahmeeinrichtung mit einem dem ersten freien Ende gegenüberliegenden zweiten Ende mit einer Verschlusseinrichtung verbunden ist und mittels der Verschlusseinrichtung in den Aufnahmebehälter eingeführt wird und der Aufnahmebehälter mit der Verschlusseinrichtung verschlossen wird.

Furthermore, a method for taking samples, in particular saliva samples, for detecting SARS-CoV-2 virus in saliva can be provided, the method comprising the following steps

• - providing a receptacle with a first opening,
• - Removal of a sample with at least one removal element arranged at a free end of a sampling device, wherein
• - the sample-taking device is connected to a closure device at a second end opposite the first free end and is inserted into the receptacle by means of the closure device and the receptacle is sealed with the closure device.

The liquid can be introduced into the receptacle, and the sampling member of the sampling device can be immersed in the treatment composition liquid upon insertion into the receptacle.

The liquid can be guided through a channel, which is arranged in a rod-shaped element of the sampling device, to a passage opening in the closure device.

The liquid can be guided to the passage opening due to capillary action and/or pressure and/or negative pressure.

The passage opening can be closed with a closing element and the closing element can be separated from the closing device.

The liquid, which is guided through the channel arranged in the rod-shaped element of the sampling device to the passage opening of the closure device, can be dispensed or poured out of the passage opening after the closing element has been separated from the closure device.

Commercially available devices such as thermocyclers are available for carrying out the POC PCR method. PCR is a method widely used in molecular biology that uses thermal cycling to produce millions to billions of copies of a given RNA/DNA sample in a very short time.

Point-of-care (PoC) analyzers have many advantages. They are mobile, light, flexible and, above all, fast. A result can be available in less than a quarter of an hour. The name clarifies the most sensible place of use for a PoC system: in the immediate vicinity of the patient and his treatment (point-of-care).

The mobile devices are rapid test systems for carrying out qualitative detection of infectious diseases. The testing is carried out on the basis of the nucleic acid amplification technique (NAT). For this reason, some product descriptions do not explicitly state "PoC-PCR device". However, the PCR method falls under the nucleic acid amplification technique. Most devices can not only detect Sars-CoV-2, but also other diseases. Abbott's ID NowTM device can also detect, for example, influenza, RS virus or streptococcal A infection.

Abbott's ID NOW ^TM is a molecular diagnostic test system for the qualitative detection of infectious diseases such as e.g. B. COVID-19 or influenza. Using isothermal nucleic acid amplification technology (NAT), the test device delivers reliable results at laboratory level.

Typical real-time q PCR systems for POC analysis can analyze multiple samples simultaneously, for example 16 or 24 or 32. In addition, the devices preferably have channels for detection, for example one or more channels for FAM/SYBR Green, VIC/JOE/HEX /TET, ABY/NED/TAMRA/Cy3, JUN, ROX/Texas RED, Cy5.

The reaction volume used is typically 5 µL - 50 µL.

For example, the rate of temperature rise at which the preferred thermal cyclers can be operated is 5°C/s heat; Cool at 5°C/s.

The PoC PCR analyzers typically support DNA probes, preferably one or more selected from DNA binding dyes (e.g. SybrGreen), hydrolysis probes (e.g. TaqMan probe) and hybridization probes (e.g. FRET probes).

In a preferred embodiment of the present invention, the qPCR test device has a housing. A test module is arranged in the housing to accommodate at least one test sample, preferably 4 to 64, in particular 16 to 24 test samples. A control module is connected to the test module, the control module being designed to control the test module so that the test module carries out qPCR tests to determine a test result. The qPCR test device preferably has a transmission module which is connected to the control module. The transmission module is designed to transmit the test result and/or status information of the qPCR test device to at least one recipient. Thus, according to a preferred embodiment of the present invention, the qPCR test device is designed to transmit the test result directly and without manual transmission of the test result to at least one recipient. As an alternative or in addition to this, status information from the qPCR test device can be transmitted to the at least one recipient by means of the transmission module. As a result, the recipient can deduce the function of the qPCR test device, which makes manipulation of the qPCR test device more difficult, for example. For example, the point-of-care qPCR test device can be set up in a pharmacy, at a doctor's office, in an ambulance, or in a mobile station or the like. Samples are then taken at the same location. The sample is tested using the qPCR test device. The test result is then automatically sent to at least one recipient. The recipient is, for example, a public/official body, in particular for registering notifiable diseases, or another registration body/database for registering the test results. In particular, the transmission is anonymous. Alternatively, the recipient can be the manufacturer of the qPCR test device, with the test result and/or status information of the qPCR test device being transmitted. Manual and therefore error-prone processing of the test results is no longer necessary. Automated filing in a central database or a central register is also possible in this way, which means that more test results can be processed in a shorter time. Furthermore, the possibility of manipulation of the test results can be reduced, since there is no intermediate step involving employees.

The test module is preferably designed to detect COVID, influenza and/or RSV (respiratory syncytial virus infections). Thus, the qPCR test device can be designed for the dedicated detection of a pathogen. Alternatively, the qPCR test device is designed so that it can detect different pathogens.

The test module is preferably designed to accommodate a plurality of test samples for testing. As a result, several test samples can be tested simultaneously for a possible viral load by the test module. This further increases the processing speed and test results are available more quickly.

A test result can preferably be transmitted. Alternatively, a large number of test results can be transmitted simultaneously. Likewise, the transmitted status information can contain a single status of the qPCR test device, which is then transmitted. As an alternative to this, the status information contains a large number of different pieces of information about the status of the qPCR test device, which are preferably transmitted simultaneously.

The transmission module is preferably designed to set up a secure connection with the at least one receiver. Here, for example, SSL is used between the qPCR test device and the recipient, with a secure connection being able to be established by means of a certificate exchange. This further reduces the possibility of manipulation and increases the security of the data.

The transmission module is preferably designed to transmit the test result to a number of recipients. As an alternative or in addition to this, the transmission module is designed to transmit status information to a number of recipients. It is thus possible for the qPCR test device not only to transmit the test result to one recipient, but rather to make it possible for the test result and/or the status information to be made available to a number of recipients at the same time. Especially in the context of a healthcare system that is interested in monitoring the spread of possible diseases, it may be necessary to send test results, in particular anonymously, to several recipients transmit, for example, to provide statistics, forecasts or information to citizens about the spread of the disease and / or the burden on the healthcare system. A manual transfer of the test results within these information systems, which would lead to delays and errors, is no longer necessary.

The status information preferably comprises one or more of a connection status of the qPCR test device, an error indicator and a test execution indicator. The connection status can be used to determine whether the qPCR test device is online and able to transmit test results via the transmission module. Error statuses of the qPCR test device can be displayed using the error indicator. In particular, if the status information is sent to the manufacturer of the qPCR test devices, the latter can derive possible repairs from this and prepare accordingly. At the same time, the error indicator ensures that only correct test results are forwarded. Thus, if the error indicator shows an error, which in particular could have an impact on the test result, then further tests by the qPCR test device are excluded or their test results are discarded. The test running indicator shows whether the qPCR test device is currently running a test. This allows the activity of the qPCR test device to be further monitored. In this way, in particular, a causal connection can be established between the execution of a test and the provision of test results, so that the provision of manipulated test results is made even more difficult.

Preferably, the test results include one or more of a test indicator, a viral load, an individual ID, and a verification indicator. The test indicator provides an indication of the test person's illness. The test indicator can in particular be binary and thus represents the result of the evaluation of the qPCR test. The test result can also contain a virus load which was determined by the qPCR test. Furthermore, the test result can contain a personal ID. In particular, the personal ID is an anonymous identification of the subject. This personal ID can be made available, for example, as a barcode, by means of which the samples are assigned. In particular, the personal ID does not include any personal information (such as name, address, passport number or the like) and is created by the test device, for example. In particular, the personal ID contains a device ID of the qPCR test device. This ensures that the personal ID of the respective qPCR test device is unique and a collision of personal IDs from different test devices is ruled out. Alternatively, the personal ID is assigned centrally to ensure the uniqueness of the personal ID. Furthermore, the test result can have a verification indicator. The verification indicator shows whether the sample is a human sample. This prevents manipulation of the sample, especially when taking the sample.

The status information is preferably transmitted periodically to the at least one recipient, in particular by means of an http request. This provides a simple transmission path for the status information to the at least one recipient. The status information can be transmitted to the at least one recipient, for example, once an hour, once a minute or every 10 seconds. The present invention is not limited to a specific frequency of transmission of the status information, as long as this frequency is high enough to ensure reliable monitoring of the qPCR test device and its functionality.

Access information for a recipient is preferably stored in the transmission module or the control module. As an alternative to this, the qPCR test device has a memory module, the memory module being connected to the control module and/or the transmission module and being designed to store access data of a recipient. This access information can include a password and/or a device ID, for example. The access information can be used to transmit test results and/or status information to the recipient. For example, if the recipient is a public/official body for registering the test results or a database, access to this public body or the database is protected. Test results and/or status information can only be transmitted to the central location or the recipient if the access information is available. If the access information does not match the access information stored with the recipient for the corresponding qPCR test device, it is not possible to transmit the test results and/or status information to this recipient.

The transmission module is preferably designed to transmit the access information for a second recipient to a first recipient. Thus, for example, access information together with the test results and/or status information is automatically transmitted from the qPCR test device directly to the first recipient. Transmission to the second recipient then takes place, with the access information being used to forward the test results to the second recipient or to store them there, as described above. In this case, the access information is encrypted, in particular as a JASON web token, from the qPCR test device to the first recipient, so that the first recipient has no knowledge of the access information. A decryption by the first recipient is not possible. Only after the second recipient has received the access information or the JASON Web Token can they decrypt the encrypted access information and use it as access information for further processing/storing the test result. The transmitted test results and/or status information are thus received and further processed by the second receiver. This allows for a flexible configuration of the flow of information from the qPCR test device to the multiple recipients. For example, the test results and/or status information can initially be transmitted from the qPCR test device to the first recipient, in particular by means of a secure SSL connection, with the first recipient being, for example, the manufacturer of the qPCR test device or a service provider . This then forwards the test results and/or status information to a second recipient. The second recipient is, for example, a public/official body such as a public health department, a pharmacy association, a doctor's association or the like, through which the test results are to be processed further. The corresponding access data, which contain access to the second recipient for storing the test results, are also transmitted by the qPCR test device, in particular in encrypted form, for example as a JASON web token. The knowledge of the access data by the manufacturer as the first recipient is thus ruled out, since decryption of the access information by the first recipient is not carried out or is ruled out. Nevertheless, it can be forwarded to the second recipient in each case. If the test results are also to be made available to other or other second recipients, it is no longer necessary to reconfigure individual qPCR test devices. Instead, the first recipient, such as the manufacturer or a service provider, can then forward it directly and centrally to this new second recipient. As a result, the flow of information becomes flexible and it is easy to adapt to whom the respective test results and/or status information are forwarded.

Furthermore, the present invention preferably relates to a system with a qPCR test device as described above and at least one first receiver.

The first receiver is preferably designed to forward test results to a second receiver.

The first recipient is preferably a manufacturer of the qPCR test device or a service provider. In particular, the second recipient is a public/official depository such as a public health department, a medical association, a pharmacy association or the like.

• - Erzeugung eines Testergebnisses und/oder einer Statusinformation und
• - Übertragung des Testergebnisses und/oder Statusinformations an mindestens einen Empfänger.

Furthermore, the present invention relates to a method for transmitting test results from a point-of-care real-time quantitative PCR test device (qPCR test device) with the steps:

• - Generation of a test result and/or status information and
• - Transmission of the test result and/or status information to at least one recipient.

The qPCR test device is preferably designed as described above.

The transmission is preferably wired or wireless using known types of transmission, for example via the Internet using LAN, WLAN, a GSM standard, or another wireless transmission technology such as Bluetooth, ZigBee, or the like. The transmission can take place via several nodes or access points. In particular, the present invention is not limited to the specific type of transmission of the test results and/or status information.

The transmission is preferably encrypted or secured, in particular by means of SSL.

The status information is preferably transmitted periodically to the at least one recipient.

The test result is preferably transmitted to several recipients. In this case, the transmission can take place directly from the qPCR test device to a number of recipients. Alternatively, the test results are forwarded by one of the recipients.

The status information is preferably only transmitted to one recipient.

Access information for access to a recipient is preferably stored on the qPCR test device. The test results can thus be sent to the at least one recipient together with the access information. In this case, the access information is required in order to have the test results and/or status information stored with the at least one recipient.

The access information is preferably transmitted to a first recipient in encrypted form, in particular using a JASON Web Token, together with the test results and/or status information. In this case, for example, the transmission can take place using SSL security. The test results are then forwarded to a second recipient by means of the access information, the access information being required to store the test results with the second recipient. The first recipient can be, for example, the manufacturer of the qPCR test device or a service provider, with the second recipient being, for example, a public/official body such as a public health department, a pharmacy association and/or medical association. Thus, the test results can only be stored for further use by the second recipient if the access information is available. The access information is forwarded without the first recipient gaining knowledge of this. It is not possible for the first recipient to decrypt the access information. It is therefore not possible for the first recipient to store manipulated test results, for example, since he has no knowledge of the access information. It is also not possible for the first receiver to read out test results unintentionally, since it has no access to the second receiver.

The consumption of test samples or further test material is preferably determined by the at least one recipient from the status information and/or planning information which is transmitted from the qPCR test device and/or the operator of the qPCR test device to the at least one recipient. The planning information can be, for example, information regarding the tests to be carried out in the future. These can, for example, be automatically forwarded to the first recipient by the operator of the qPCR test device. In particular, the recipient is the manufacturer of the qPCR test device or a service provider. If the number of available test samples or the availability of further test material falls below a specified limit, a signal is triggered. This signal can be an optical or acoustic signal, which is output by the at least one receiver. Alternatively, the signal is a control signal which triggers the automated provision of further test samples or further test material to the operator of the qPCR test device. The probable amount of required test samples and/or test material can be determined using the status information and/or planning information, and the number of test samples to be subsequently delivered or the scope of the test material to be subsequently delivered can thus be adjusted.

Exemplary embodiments of the present invention are explained in more detail below with reference to the drawings.

• 1 eine Vorrichtung zur Aufnahme von Proben gemäß einer Ausführungsform der vorliegenden Erfindung,
• 2 die Aufnahme von Proben mittels einer Ausführungsform der erfindungsgemäßen Vorrichtung,
• 3 eine erfindungsgemäße Ausführungsform der Vorrichtung mit verschlossener Verschlusseinrichtung,
• 4 Vorrichtung aus 3 mit abgetrenntem Abschlusselement,
• 5a Vorrichtung gemäß 4 bei der zu analysierende Probenflüssigkeit in ein PCR-Gefäß ausgeschüttet wird,
• 5b Vorrichtung gemäß 9 bei der zu analysierende Probenflüssigkeit in ein PCR-Gefäß ausgeschüttet wird,
• 6 Vorrichtung gemäß 7 in geöffnetem Zustand und mit Swab
• 7 eine erfindungsgemäße Ausführungsform der Vorrichtung mit verschlossener Verschlusseinrichtung
• 8 Einscannen eines Identificationscodes auf einer einer Ausführungsform einer erfindungsemäßen Vorrichtung, und
• 9 Vorrichtung aus 6 mit abgetrenntem Abschlusselement

They show schematically:

• 1 a device for collecting samples according to an embodiment of the present invention,
• 2 the recording of samples by means of an embodiment of the device according to the invention,
• 3 an embodiment of the device according to the invention with a closed closure device,
• 4 device off 3 with separated end element,
• 5a Device according to 4 in which the sample liquid to be analyzed is poured into a PCR vessel,
• 5b Device according to 9 in which the sample liquid to be analyzed is poured into a PCR vessel,
• 6 Device according to 7 in open condition and with swab
• 7 an embodiment of the device according to the invention with a closed closure device
• 8th Scanning an identification code on an embodiment of a device according to the invention, and
• 9 device off 6 with detached end element

1 shows an embodiment of the device according to the invention for taking samples, in particular saliva samples or nasopharygeal swab samples for carrying out a PCR analysis method for determining pathogenic microorganisms, in particular pathogenic viruses, especially viruses that cause respiratory diseases, in particular corona viruses, especially SARS-CoV-2 viruses . The device has a receiving container 2 which has a first opening 4 .

Furthermore, a closure device 6 is provided, which is adapted to the opening 4 of the receptacle 2 so that the opening 4 of the receptacle 2 can be closed with the closure device 6 . Furthermore, a sampling device 8 is shown, which has at least one first sampling element 12 on a first free end 10 . The sample can be removed with the removal element 12 . The extraction element 12 can consist of a material which can be absorbent or adhesive in relation to liquids. That is, the extraction element can absorb the liquid or the liquid adheres to the extraction element.

An absorbent material can be, for example, an element made of cotton wool. The removal element preferably comprises cotton threads or Dacron fibers. In special embodiments, the removal element has microfibers. These improve the recording and increase the recording volume of the sample material.

The sampling device 8 is connected to the closure device 6 at the second end 14 opposite the first free end 10 . The sampling device 8 can be introduced into the receptacle 2 by means of the closure device 6 .

The sampling device 8 has at least one hollow rod-shaped element 16 . The removal element 12 is arranged at the free end of the rod-shaped element 16 . The hollow rod-shaped element 16 forms a channel 18 on the inside. The rod-shaped element 16 and thus the sampling device 8 are connected to the closure device 6 in this embodiment.

The rod-shaped element 16 preferably comprises a plastic, preferably comprising polyethylene and/or polypropylene.

The closure device 6 has a through opening 20 . The sampling element and thus the rod-shaped element 16 are connected to the closure device 6 in such a way that the channel 18 opens into the through-opening 20 or is arranged in it. The rod-shaped element 18 can thus be arranged in the passage opening 20 and connected to the closure device 6 or connected to the closure device 6 at the end facing the sampling device 8 so that the channel 18 opens into the passage opening 20 .

In 2 shows how the sample, in particular a saliva sample, can be taken. For this purpose, the sampling device 8 can be inserted through the nose or through the mouth and the sample can be taken with the sampling element 12 .

In 3 shows how the receptacle 2 is closed with the closure device 6 . In doing so, the closure device closes the opening 4 . The receptacle 2 can be closed in a liquid-tight and preferably air-tight manner with a closure device. The length of the sampling device 8 is selected in such a way that the sampling device 8 does not hit the bottom of the receptacle 2 when the closure device 6 is closed. However, the sampling device 8 is preferably long enough for the liquid treatment composition to be in contact with the sampling element 12 for carrying out a PCR test on site (Point of Care; PoC) or for the sampling element to be immersed in the liquid.

After a sample has been taken with the sampling element 12 , the sampling device 8 can be inserted into the receiving container 2 . The opening 4 can be closed by means of the closing device 6 and the entire device can be transported safely without contamination getting onto the sample.

According to the invention, the liquid treatment composition for on-site (Point of Care; PoC) implementation of a PCR test is arranged in the receptacle 2, so that after the sample has been taken, the sample extraction device 8 is inserted into the receptacle 2 and the extraction element 12 is immersed directly in the liquid will. The opening 4 can be closed by means of the closure device 6 .

It is also in 3 a closing element 22 is shown, which closes the passage opening 20 of the closure element 6 to the outside. The closing element 22 is detachably connected to the closure element 6 . As long as the closure element 22 is connected to the closure element 6, no liquid can escape through the channel 18 and the through-opening 20 to the outside.

In 4 is the device according to 3 shown, but with the difference that the closing element 22 has been separated from the closure element 6 . The closure element 22 can preferably be separated from the closure element 6 by bending.

The hollow rod-shaped element 16 can have at least one opening at the free end 10 . The opening can form the opening of the channel arranged in the rod-shaped element. In the present case, this can be the opening 24 that is arranged in the removal element 12 . The liquid that passes through the removal element 12 can then be guided through the channel 18 to the through-opening 22 and can exit there from the receiving container 2 when the closure element 22 has been separated. Due to capillary action and/or pressure and/or negative pressure, the liquid can be guided to the passage opening 22 and can exit there from the receiving container 2 when the closure element 22 has been separated.

For example, this is in 5a shown. There, preparation composition for carrying out a PCR test on site (Point of Care; PoC), which has been brought into contact with the biological sample, is poured out of the receiving container 2 into a first PCR vessel A1. This can then be used for further PCR testing directly on site.

The opening in the rod-shaped element 16 can also be arranged in the peripheral wall and/or can also be arranged in the area which adjoins the closure device 6 . At least one opening can also be arranged in this area and additionally another opening in the area of the removal element 12.

7 shows an embodiment of the device according to the invention for taking samples, in particular saliva samples or nasopharygeal swab samples, for carrying out a PCR analysis method for determining pathogenic microorganisms, in particular pathogenic viruses, especially viruses that cause respiratory diseases, in particular corona viruses, especially SARS-CoV-2 viruses. The device has a receiving container 2 which has a first opening 4 .

Furthermore, a closure device 6 is provided, which is adapted to the opening 4 of the receptacle 2 so that the opening 4 of the receptacle 2 can be closed with the closure device 6 .

The closure device 6 has a through opening (not shown). Furthermore, a closing element 22 is shown, which closes the passage opening of the closure element 6 to the outside. The closing element 22 is detachably connected to the closure element 6 . As long as the closure element 22 is connected to the closure element 6, no liquid can escape through the channel 18 and the through-opening 20 to the outside. Furthermore, the receiving container can have an identification code 26 .

6 shows the embodiment according to FIG 7 in which the closure element 6 has been separated from the receptacle 2. After a sample has been taken with the sampling element 30 , the sampling device 8 can be inserted into the receiving container 2 . The collected sample is brought into contact with the liquid treatment composition in the collection container for the on-site (Point of Care; PoC) implementation of a PCR test. The opening 4 can be closed by means of the closing device 6 and the entire device can be transported safely without contamination getting onto the sample.

According to the invention, the liquid treatment composition for on-site (Point of Care; PoC) implementation of a PCR test is arranged in the receptacle 2, so that after the sample has been taken, the sample extraction device 8 is inserted into the receptacle 2 and the extraction element 30 is immersed directly in the liquid will. The opening 4 can be closed by means of the closure device 6 . The sampling element 8 comprises a rod-shaped element 28 and the sampling element 30.

8th shows the embodiment according to FIG 7 with an identification code 26 which is scanned by a scanner 24.

In 9 is the device according to 7 shown, but with the difference that the closing element 22 has been separated from the closure element 6 . The closure element 22 can preferably be separated from the closure element 6 by bending.

It is also in 9 a closing element 22 is shown, which has been separated and which previously closes the passage opening 20 of the closure element 6 to the outside. The closing element 22 is detachably connected to the closure element 6 . As long as the closure element 22 is connected to the closure element 6, no liquid can escape through the through-opening 20 to the outside.

The liquid preparation composition for the on-site (Point of Care; PoC) implementation of a PCR test, which has been brought into contact with the biological sample, can be poured out of the receiving container 2 into a first PCR vessel A1 ( 5b) . This can then be used for further PCR testing directly on site.

Example: PoC PCR for SARS CoV-2 viruses

The in the and The device according to the invention shown for collecting biological samples contains an aqueous preparation composition for carrying out a PCR test on site, comprising guanidinium thiocyanate, surfactant, 2 different RNase inhibitors, an antibody that neutralizes SARS-CoV-2 viruses and biotin.

Nasospharygeal secretion is removed from a patient with a swab and brought into contact with the treatment composition in the device according to the invention. The treatment composition combined with the secretion is then incubated for 5 minutes at 20°C. 1 drop (30 µl) is filled through the passage opening in the cap into a PCR sample tube containing a PCR reaction mixture comprising polymerase and primers and probes for the detection of SARS CoV-2 viruses. The PCR sample container is then placed directly in a PoC-PCR test device (thermocycler). The result is available after 10 to 30 minutes.

Claims (23)

Device (1) for receiving biological samples for carrying out a PCR analysis method for determining pathogenic microorganisms, in particular pathogenic viruses, especially viruses that cause respiratory diseases, with a receiving container (2) with a first opening (4), a closure device ( 6), which is adapted to the opening (4) of the receptacle (2), so that the opening (4) of the receptacle (2) can be closed with the closure device (6), the closure device (6) having a through-opening (20) characterized in that the receiving container (2) contains a liquid preparation composition for carrying out a PCR test on site (Point of Care; PoC). Device according to claim 1 , characterized in that the device also has a sampling device (8) which has at least one first sampling element (12) on a first free end (10) with which the sample can be removed, and the sampling device (8) in the receptacle (2) is insertable. Device according to claim 2 , characterized in that the sampling device (8) is connected to the closure device (6) at a second end (14) opposite the first free end (10), so that the sampling device (8) can be inserted into the receptacle by means of the closure device (6). (2) is insertable. Device according to one of Claims 1 until 3 , characterized in that the passage opening (20) of the closure device (6) is closed by means of a closure element (22), the closure element (22) being separably fastened to the closure element. Device according to one of claims 2 until 4 , characterized in that the sampling device (8) has at least one hollow rod-shaped element (16), at the free end of which the sampling element (12) is arranged, the hollow rod-shaped element (16) forming a channel (18) on the inside. Device according to one of claims 2 until 5 , characterized in that the rod-shaped element (16) is connected to the closure device (6) in such a way that the channel (18) of the rod-shaped element (16) opens into the through-opening (20) or is arranged in this. device after claim 6 , characterized in that the passage opening of the closure element is closed on the side opposite the sampling element by means of a closing element which is separably fastened to the closure element. Device according to one of Claims 4 until 7 , characterized in that the closing element can be separated from the closure element by bending. Device according to one of claims 2 until 8th , characterized in that the hollow rod-shaped element has at least one opening at the free end. device after claim 9 , characterized in that the end of the channel arranged in the rod-shaped element forms the opening at the free end. device after claim 9 or 10 , characterized in that the opening located at the free end is located in the wall of the rod-shaped element. Device according to one of Claims 1 until 11 , characterized in that the device, in particular the receiving container, has an identification code. Device according to one of Claims 1 until 12 , characterized in that the viruses are corona viruses, in particular SARS CoV-2 viruses. Device according to one of Claims 1 until 12 , characterized in that one or more viruses are selected from the group consisting of SARS CoV-2 virus, influenza virus and adenovirus. Device according to one or more of Claims 1 until 14 , characterized in that the PCR test is a quantitative PCR method (qPCR) or a quantitative real-time PCR (RT-qPCR). Device according to one or more of Claims 1 until 15 , characterized in that the biological sample is saliva and/or nasopharyngeal secretion. Device according to one or more of Claims 1 until 16 , characterized in that the liquid treatment composition contains guanidinium thiocyanate. Device according to one or more of Claims 1 until 17 , characterized in that the liquid treatment composition contains one or more surfactants. Device according to one or more of Claims 1 until 18 , characterized in that the liquid treatment composition contains one or more RNAase inhibitors, preferably 2 different RNase inhibitors. Device according to one or more of Claims 1 until 19 , characterized in that the liquid treatment composition contains a buffer. Device according to one or more of Claims 1 until 20 , characterized in that the liquid treatment composition contains biotin. Use of the device according to one of Claims 1 until 21 for a PoC PCR test procedure. Kit comprising a) a device according to any one of Claims 1 until 21 , b) optionally a sampling device and c) optionally a separate container with a PCR reaction mixture.

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