Detection of wet media in a bioanalysis device
By introducing a humidity sensor and an analysis unit into the biological analysis device to automatically detect and monitor the presence of humid media, the problem of the lack of automatic detection methods in the existing technology is solved, and the reliability and efficiency of the operation are improved.
Patent Information
- Application Number
- CN202380046735.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2022-06-13
- Filing Date
- 2023-06-13
- Publication Date
- 2025-01-24
AI Technical Summary
The lack of methods for automatically detecting the presence and state of growth media in existing bioanalytical devices makes it difficult for operators to determine whether the media exists or what is the state, especially during prolonged sampling.
A biological analysis device is designed, including a housing, a humidity sensor and an analysis unit. The internal space of the housing is used to accommodate humid media. The humidity sensor measures the internal humidity and provides an output signal. The analysis unit detects the presence of the humid medium by receiving the output signal and analyzing changes in humidity over time.
Automatic detection and monitoring of the presence of moist media in biological analysis devices is realized, avoiding the necessity of manual inspection, especially during long-term sampling processes, and improving the reliability and efficiency of operations.
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Figure CN119365767A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to a bioanalysis device and a method of using the device. Background Art
[0002] Many bioanalytical devices use growth media (e.g., in the form of plates and / or liquids) to collect, count, grow, or monitor cells or bacterial spores. These devices can benefit from automatic detection of the presence of growth media to trigger specific actions.
[0003] An example is a microbial air sampler, which extracts target particles from the air onto or into a suitable growth medium. The currently preferred method is to use a gas / air stream directed toward the growth medium. The accelerated particles impact a nutrient plate for subsequent analysis. A potential risk is that the operator forgets to insert the required medium (e.g., a nutrient plate) before a measurement, or that the operator forgets to replace an already inserted medium before a subsequent measurement.
[0004] Currently, there are no available methods to infer the presence and status of such mediators in biological analysis devices such as microbial air samplers.
[0005] For stationary tools such as automated microscopes, optical, electrical and mechanical solutions exist to detect the presence of shapes and sizes of growth medium plates (usually in the form of round Petri dishes).
[0006] In contrast, the presence and / or status of the growth medium in bioanalytical devices is not automatically assessed. In particular, in applications such as microbial air sampling, there has been no simple and integrated setup for such a purpose to date. Therefore, the presence of the growth medium during sampling is primarily ensured by standardized work procedures. This means that it is not possible to infer whether the plate is in the current operating system. Especially for long sampling durations, this is a serious limitation, since opening the instrument for manual inspection is not possible without invalidating the ongoing measurement. Summary of the invention
[0007] Therefore, based on the above, the problem to be solved by the present invention is to provide a bioanalytical device and a corresponding method which improves on the above mentioned difficulties in detecting the presence of a moist medium such as a growth medium in a bioanalytical device.
[0008] This problem is solved by a bioanalysis device having the features of claim 1 and a method having the features of claim 15 .
[0009] Preferred embodiments of these aspects of the invention are set out in the respective dependent claims and are also described below.
[0010] According to claim 1, a biological analysis device is disclosed, comprising:
[0011] - a housing comprising an interior space configured to accommodate a moist medium at a location in the interior space,
[0012] a humidity sensor configured to measure the humidity in the interior space and to provide an output signal indicative of the humidity, and
[0013] - an analysis unit operatively connected to the humidity sensor for receiving the output signal, wherein the analysis unit is configured to derive the humidity variation over time from the output signal for detecting the presence of the moist medium in the interior space of the housing.
[0014] Thus, advantageously, the present invention provides a means of detecting and monitoring the presence of a moist medium, such as a moist growth medium, in a bioanalytical device. The moist medium may be an aqueous medium. However, the moist medium may also be a liquid.
[0015] In particular, the present invention is applicable to a wide range of applications, such as microbial air sampling. The present invention is easy to implement, can be implemented in miniature size, and has no direct contact between the medium and the detection humidity sensor during operation, which simplifies its implementation.
[0016] According to a preferred embodiment of the bioanalysis device, the internal space of the shell forms a flow channel, wherein the shell is configured to accommodate a wet medium at the position in the internal space, preferably to accommodate a carrier carrying the wet medium, so that the flow channel extends along the wet medium, in particular along the carrier carrying the wet medium.
[0017] Preferably, in one embodiment, the flow channel extends from the inlet of the housing to the outlet of the housing. The flow channel may also form a closed loop.
[0018] According to yet another embodiment of the bioanalysis device, the bioanalysis device is configured to provide a gas flow through the flow channel, so that when the humidified medium is arranged in the inner space of the housing, the gas flow passes through the humidified medium (e.g., carried by the carrier). In particular, the gas can be ambient air, but can also be any other gas used, for example, in cell culture.
[0019] In particular, in one embodiment, the bioanalysis device is configured to draw in a gas flow through the inlet and discharge the gas flow through the outlet.
[0020] According to another embodiment, the humidity sensor is arranged in the flow channel downstream of the position, i.e., downstream of the humid medium (particularly downstream of the carrier carrying the humid medium when the carrier is arranged in the inner space of the shell as expected at the position), so that the air flow first passes through the humid medium and then through the humidity sensor.
[0021] In addition, according to an embodiment of the present invention, the bioanalysis device further comprises a control unit configured to control the airflow. In particular, controlling the airflow may mean or include turning on or off an airflow generating device of the bioanalysis device, such as a fan, or opening or closing a valve of the bioanalysis device to allow the pressurized gas to flow.
[0022] According to a preferred embodiment of the invention, the analyzing unit is configured to determine the change in humidity over time when the air flow is activated (eg through the flow channel).
[0023] Furthermore, according to a preferred embodiment, the analysis unit is configured to detect the presence of a humid medium in the interior space (particularly carried by said carrier) when the determined variation of the relative humidity over time forms a peak, particularly at said start of the air flow.
[0024] Preferably, according to an embodiment of the present invention, the moist medium is a moist growth medium for promoting the growth of microorganisms. In particular, the carrier is a plate, such as a petri dish.
[0025] Furthermore, according to a preferred embodiment, the bioanalysis device is configured to allow an airflow to pass along the moist medium when the moist medium (or a carrier carrying the moist medium) is arranged in the internal space, so that particulate matter contained in the airflow is deposited on the moist medium. In particular, the particulate matter may be a microorganism, wherein the moist medium here is a moist growth medium for promoting the growth of the microorganism to detect the microorganism (e.g., by examining the cultured microorganism).
[0026] In addition, according to an embodiment, the bioanalysis device includes an airflow generating device for generating the airflow. In particular, the airflow generating device can be a fan, i.e. a power machine for generating an airflow (e.g., an air flow), or a compressor, or a source of a pressurized medium (in particular, a gas). The fan can include a rotating arrangement of blades or paddles. In contrast, a compressor can also generate an airflow, but increases the pressure of the gas by reducing its volume.
[0027] Furthermore, according to a preferred embodiment of the present invention, the humidity sensor is a relative humidity sensor configured to measure the relative humidity in the internal space, the output signal indicating the relative humidity, or wherein the humidity sensor is an absolute humidity sensor configured to measure the absolute humidity in the internal space, the output signal indicating the absolute humidity. According to one embodiment, the bioanalysis device further comprises a temperature sensor, and is configured to derive the relative humidity from the measured absolute humidity and the temperature measured by the temperature sensor.
[0028] According to a further preferred embodiment, the housing comprises an openable cover to allow access to the inner space, so that a carrier carrying the moist medium can be accommodated in the inner space in an open state of the cover and is surrounded by the housing in a closed state of the cover.
[0029] According to a preferred embodiment of the present invention, the inlet is formed in the cover, wherein preferably the inlet is formed by a plurality of through openings formed in the cover.
[0030] Furthermore, according to a preferred embodiment of the bioanalysis device, the bioanalysis device is configured to accommodate the carrier in the internal space so that the top surface of the moist medium faces the inlet.
[0031] According to another aspect of the invention, a method for detecting the presence of a carrier carrying a moist medium in an inner space of a bioanalytical device, the bioanalytical device being configured to receive a moist medium (e.g. carried by the carrier, see e.g. above) at a defined position in the inner space, wherein the method comprises the following steps:
[0032] - starting a gas flow (for example air) from the defined position towards a measurement site in the inner space,
[0033] - measuring the humidity at said measurement location,
[0034] The presence of the moist medium in the interior (for example carried by the carrier) is automatically detected if the variation of the measured relative humidity forms a local maximum, in particular at the beginning of the air flow.
[0035] Preferably, the bioanalysis device according to the present invention is used to implement the method according to the present invention. In particular, the method can be further explained in detail by combining the various embodiments described herein with the bioanalysis device according to the present invention. BRIEF DESCRIPTION OF THE DRAWINGS
[0036] In the following, embodiments of the present invention and other features, advantages and other aspects of the present invention will be described with reference to the accompanying drawings, in which
[0037] Figure 1 An embodiment of a bioanalysis device according to the present invention is shown.
[0038] Figure 2A yes Figure 1 A schematic cross-sectional view of the device shown,
[0039] Figure 2B A schematic diagram showing a flow channel according to an embodiment of a bioanalysis device; and
[0040] Figure 3 The measuring principle according to an embodiment of the invention is shown. DETAILED DESCRIPTION
[0041] refer to Figure 1 and 2A , which shows an embodiment of a bioanalytical device 1 according to the invention, which advantageously utilizes the fact that a moist medium 30, such as any growth medium for organisms / cells / spores, e.g. carried by a suitable carrier 3, contains a considerable amount of water, wherein some of the water will continuously evaporate from the medium 30 into the surrounding gas (note that the space around the nutrient plate / carrier 3 is usually limited).
[0042] In particular, if Figure 1 and 2A As shown, the device 1 comprises a housing 2 defining an inner space 20, the inner space being configured to accommodate the carrier 3 in a defined position, the carrier 3 carrying the moist medium 30. When the humidity sensor 4 can now be placed in flow connection with the gas G surrounding the moist medium 30, the presence of the moist medium 30 can be detected by an increase in humidity (e.g. relative humidity or absolute humidity) measured by the sensor 4. Therefore, the device 1 comprises a humidity sensor 4, which is configured to measure the humidity in the inner space 20 and provide an output signal indicative of the humidity, wherein the sensor 4 is preferably placed downstream of the moist medium 30 in the flow channel 20 formed by the inner space 20, so that the air flow G flowing through the flow channel 20 transmits the humidity of the moist medium 30 towards the humidity sensor 4. Furthermore, the device 1 preferably comprises an analysis unit 5 (e.g. in the form of an electronic circuit), which is operatively connected to the humidity sensor 4 so as to receive the output signal, wherein the analysis unit 5 is configured to derive the change in humidity over time from the output signal for detecting the presence of the carrier 3 carrying the moist medium 30 in the inner space 20 of the housing 2.
[0043] Here, the humidity is measured continuously or repeatedly, and the presence of a moist (e.g. growing) medium 30 results in an increase in the humidity detected by the humidity sensor 4 at the start of the airflow G / measurement, while the absence of a moist medium 30 results in a constant humidity. Thus, if no medium 30, such as a nutrient plate, is present, the humidity will not (significantly) change at the start of the airflow G.
[0044] Thus, the presence of a moist medium 30 can be inferred from the detection of a changing humidity (signal above an upper threshold), and the absence of a moist medium 30 can be inferred from the non-detection of a changing humidity (signal below a lower threshold).
[0045] In particular, according to an embodiment of the present invention, the bioanalysis device 1 may be a microbial air sampler 1 , wherein the airflow G preferably first passes through the moist growth medium 30 in order to impact the particles upstream of the location of the humidity sensor 4 .
[0046] In particular, Figure 3 1 shows a preferred measuring principle, which shows the relationship between the air flow G and time in the uppermost diagram. If a moist medium 30 is arranged in the device 1 at time t0, the humidity detected by the sensor 4 (here the relative humidity RH measured by the sensor 4 in the form of a relative humidity sensor 4) increases with the switching on of the air flow G. This can be detected as a peak P in the derivative of the relative humidity dRH with respect to time, as Figure 3 as shown in the bottom figure.
[0047] Furthermore, the information about the presence / absence of the moist medium 30 can be used to control the process.
[0048] For example:
[0049] - If medium 30 is detected: continue gas (eg air) sampling.
[0050] - If no medium 30 is detected, then any of the following depending on the instrument configuration:
[0051] - Automatically terminate the sampling process and notify the user and / or higher-level system.
[0052] - Raise an alarm and optionally allow the user and / or a higher level system to decide whether to continue or abort the sampling process.
[0053] In particular, evaluating the change in relative humidity over time (dRH / dt or dRH) rather than absolute humidity enables the detection mechanism to be independent of ambient conditions. Even in a start-stop cycle, where the humidity in the system is already high from the last run, where a carrier 3 carrying a moist medium 30 (e.g. a nutrient plate) is located in the device 1 (a similar principle is sometimes referred to as a stopped flow technique for analyte accumulation in diagnostic biosensors), the presence of moist (e.g. growth) medium can be detected.
[0054] also, Figure 2B A schematic flow channel 20 according to an embodiment of the present invention is shown. Accordingly, the device 1 may include a thermal mass flow sensor 40, and the relative humidity sensor 4 downstream of the flow sensor 40 may further include sensors for measuring the temperature and absolute pressure of the sampled gas (e.g., air). Since all these sensors are available in miniature form, the device 1 and method according to the present invention can be implemented not only in large-scale devices, but also suitable for portable applications.
[0055] like Figure 2B As shown, a thermal mass flow sensor 40 can be used in a bypass configuration to measure the pressure drop along the flow channel. The pressure drop can be artificially enlarged using a flow constriction (e.g. an orifice or a venturi configuration). To measure relative humidity (and in particular temperature T and absolute pressure p), a corresponding sensor 4 is preferably located in the flow channel 20 before, after or in parallel with the mass flow sensor 40.
[0056] In addition, according to Figure 2A In the embodiment indicated in, in particular when the device 1 is used as a portable microbial air sampler (as an example of a particle monitoring system) 1, the device 1 is preferably configured to generate an airflow G (usually air) by sucking the gas G into an inlet 21 of a cover 23 of a housing 2 at the top of the device 1, wherein the inlet 21 can be formed by perforating the cover 23. The airflow G then passes through a carrier 3 and a moist medium 30 carried by the carrier 3 (for example, a nutrient plate such as an agar plate). The airflow G can be generated by an airflow generating device 6, such as a fan 6, which draws the airflow G into the flow channel 20 through the inlet 21, wherein the airflow generating device 6 can be arranged downstream of the carrier 3 / medium 30 in the airflow channel 20. In particular, the humidity sensor 4 (or Figure 2B The sensor path shown in the figure can be arranged downstream of the airflow generating device 6, wherein the sensor 4 measures the change of relative or absolute humidity to detect the presence of the moist medium 30 by the analysis unit 5, which evaluates the output signal of the humidity sensor 4, for example as described above. The airflow generating device 6 can be controlled by a control unit 7, which turns the airflow generating device on or off or can control its rotor speed. Finally, the airflow G is discharged through the outlet 22 formed in the housing 2.
[0057] Preferably, the openable cover 23 allows easy access to the inner space 20, so that in the open state of the cover 23, the carrier 3 carrying the moist medium 30 can be accommodated in the inner space 20 at a defined position. The device 1 may include a support 31 on which the carrier can be placed, which support 31 can also fix the carrier 3 parallel to the cover 23 to prevent the carrier 3 from moving in the inner space 20. Once the cover 23 is closed, the housing 2 surrounds the carrier 3 and the moist medium 30 thereon. In particular, the gas generating device 6 can be arranged below the support 31, facing the lower side 31a of the support 31, with its lower side 31a facing away from the carrier 3 placed thereon. The air flow G sucked in through the inlet / perforation 21 is therefore sucked in along the medium 30, then deflected around the carrier 3 and the support 31 in the flow channel 20, sucked in by the air flow generating device 6 (for example a fan), and along the humidity sensor 4 (in particular, if present, along the flow sensor 40, see Figure 2B )pass.
[0058] As mentioned above, when there is no moist medium 30 (e.g., moist medium of a nutrient plate) in the interior space on the support 31, the relative humidity sensor 4 does not measure significant humidity changes before the start of the measurement, after the start of the measurement, during the measurement, and after the measurement / flow stop - the relative humidity remains essentially constant over time. This characteristic of the output signal of the sensor 4 can be evaluated by the analysis device 5, which then detects that there is no moist medium 30 in the interior space 20 on the support 31.
[0059] When a carrier 3 (e.g. a nutrient plate) with a moist medium 30 is inserted, the start of the airflow G delivers gas (e.g. air) that has been in close contact with the humidified nutrient plate 3 since the plate 3 was inserted into the interior space 20 of the device 1. This volume of airflow G has a significantly higher relative humidity than the medium sensed before the start of the airflow G. During the constant flow rate, a constant relative humidity will be seen (higher than in the case without the nutrient plate 3). When the device is stopped, the relative humidity level will remain high (see Figure 3 ).
[0060] When the airflow G is restarted, the accumulated volume close to the nutrient plate 3 during the stop of the airflow G will pass the relative humidity sensor 4. This will trigger the detection of a relative humidity peak P, even if the relative humidity level was already high in the previous measurement. Therefore, this "stop flow" caused peak can be used to detect the presence of a carrier 3 with a moist medium 30 (e.g. a nutrient plate, such as an agar plate 3) in the device 1.
[0061] Due to its features, the invention allows the measuring principle of the invention to be easily integrated into various devices and processes, reducing costs, achieving high precision and thus increasing process reliability. Furthermore, the invention is not influenced by environmental conditions (temperature, absolute pressure, relative humidity). The differential signal analysis makes the detection of the corresponding wet media independent of the previous configuration and short-term history of the instrument.
Claims
1. A biological analysis device (1), comprising: a housing (2) comprising an interior space (20) configured to accommodate a moist medium (30) at a location in the interior space (20), a humidity sensor (4) configured to measure the humidity in the interior space (20) and to provide an output signal indicative of the humidity, and - an analysis unit (5) operably connected to the humidity sensor (4) to receive the output signal, wherein the analysis unit (5) is configured to derive the change in humidity over time from the output signal for detecting the presence of the humid medium (30) in the inner space (20) of the housing (2).
2. The bioanalyzer according to claim 1, wherein: The inner space (20) forms a flow channel, wherein the housing (2) is configured to accommodate a carrier (3) carrying the wet medium (30) in the inner space (20), so that the flow channel (20) extends along the wet medium (30).
3. The bioanalyzer according to claim 2, wherein: The flow channel (20) extends from an inlet (21) of the housing (2) to an outlet (22) of the housing (2).
4. The bioanalyzer according to claim 2 or 3, wherein: The bioanalysis device (1) is configured to provide an airflow (G) through the flow channel (20) so that when the carrier (3) is arranged in the internal space (20), the airflow passes through the moist medium (30) carried by the carrier (3).
5. The bioanalyzer according to any one of claims 2 to 4, wherein: The humidity sensor (4) is arranged in the flow channel (20) downstream of the location.
6. The bioanalyzer according to claim 4 or 5, wherein: The bioanalysis device (1) further comprises a control unit (7) configured to control the gas flow (G).
7. A bioanalysis device according to any one of the preceding claims, wherein: The analysis unit (5) is configured to determine the change in humidity over time, in particular in an interval starting before activation of the air flow (G) and ending after activation of the air flow (G).
8. A bioanalysis device according to any one of the preceding claims, wherein: The analysis unit (5) is configured to detect the presence of the humid medium (30) in the interior space (20) when the determined variation of the relative humidity over time forms a local maximum (P).
9. A bioanalysis device according to any one of the preceding claims, wherein: The moist medium (30) is a moist growth medium that promotes the growth of microorganisms.
10. The bioanalyzer according to claim 4 and any one of claims 5 to 9 depending on claim 4, wherein: The bioanalysis device is configured to allow the airflow (G) to pass along the moist medium (30) when the carrier (3) is arranged in the internal space (20), so that particulate matter contained in the airflow (G) settles on the moist medium (30).
11. The bioanalysis device according to claim 4 or one of claims 5 to 10 dependent on claim 4, wherein: The bioanalysis device (1) comprises an airflow generating device (6) for generating the airflow (G).
12. A bioanalysis device according to any one of the preceding claims, wherein The humidity sensor (4) is a relative humidity sensor configured to measure the relative humidity in the interior space (20), and the output signal indicates the relative humidity, or the humidity sensor (4) is an absolute humidity sensor configured to measure the absolute humidity in the interior space (20), and the output signal indicates the absolute humidity.
13. A bioanalysis device according to any one of the preceding claims, wherein: The housing (2) comprises a cover (23) which can be opened to allow access to the inner space (20), so that the moist medium (30) can be accommodated in the inner space (20) when the cover (23) is open, and is surrounded by the housing (2) when the cover (23) is closed.
14. The bioanalysis device according to claims 3 and 13, wherein: The inlet (21) is formed in the cover (23).
15. A method for detecting the presence of a moist medium (30) in an interior space (20) of a bioanalytical device (1), the bioanalytical device (1) being configured to contain the moist medium (30) at a location in the interior space (20), wherein the method comprises the following steps: - allowing a gas flow (G) to flow from said position towards a measurement site in said inner space (20), - measuring the humidity at said measurement location, - if the measured change in humidity forms a local maximum (P), the presence of the moist medium (30) in the interior (20) is detected.