DE102009048790B4 - Biosensor device with filter monitoring device - Google Patents

Abstract

Biosensor device (10) for detecting biological particles with a detection device (12) for detecting the biological particles present in the sample, wherein the detection device (12) comprises a filter (14) for collecting biological particles for detection, wherein a filter monitoring device (32 ) is provided with a voltage measuring device (52) for measuring a mechanical stress on the filter (14) for automatically monitoring the function of the filter (14).

Description

The invention relates to a biosensor device for detecting biological particles with a detection device having a filter for collecting biological particles.

Known biosensor devices, which detect the presence of biological particles such as bacteria, viruses, fungi, yeasts and other microorganisms, often have a filter designed to collect and concentrate the biological particles. A sample containing the biological particles, for example a liquid or a gas, is passed either over or through the filter. The filter is designed in such a way that the biological particles to be detected remain suspended while the sample itself continues to flow.

For example, such biosensor devices use filters that may be formed as membrane filters of various materials. These membrane filters have a porosity which is adapted to the particles to be detected. Thus, the particles can not penetrate the filter, while the surrounding fluid, in which the particles are present, can flow through the filter.

However, such filters have the disadvantage that the pores, which are designed to trap the biological particles, just enforce this trapping process with the biological particles. In the worst case, this addition renders the filter unusable for further detection after the first use. Examples of biosensor devices for the detection of biological particles which have a membrane filter for filtering out biological particles for detection can be found for example in US Pat WO2005 / 102528A1 and the WO03 / 005013A1 ,

Like in the US 5726026 A and the US2006 / 0257941A1 described, the problem of the clogged filter is solved in that it is disposed of after performing the detection step. This prevents contamination between successive samples and guarantees the functionality of the filter in all tests performed.

Recently, however, there is a desire for a high-quality filter, which has a high resistance especially against chemicals used in the detection as well as other external influences such as bumps.

According to the German patent application DE 03/005013 772 A1 , to which reference is expressly made for further details, it is proposed to produce such a durable diamond filter. However, such filters are too expensive to dispose of after each detection step.

Therefore, there is a desire that the filter can be cleaned in order to use it again. A detection device, in which the possibility for cleaning the filter is described in order to reuse it, is in the WO2008 / 135452A2 disclosed. Here it is described that the filter is usable several times by being regenerated and / or conditioned by suitable chemicals and this is made possible by appropriately controlled pumps and valves.

However, routine cleaning of the filter, even if performed after each detection test, does not guarantee the full functionality of the filter so prepared. Despite cleaning, biological particles can still clog the filter pores and thus contaminate the subsequent sample. A clean test result can not be guaranteed by the mere standard cleaning of the filter.

Further, cleaning can not guarantee that the filter will not be damaged over time. Even if the filter is completely freed from the adding biological particles by the regular cleaning process, the detection can still be affected by the fact that the filter has a fracture or crack and thus is no longer suitable for filtering out the biological particles from the sample.

Therefore, there is a need to provide a biosensor device improved in view of the aforementioned problems.

The US 2002/0160363 A1 describes an analysis device with a sensor array, are bound in the biological particles for detection via optical means to receptor particles. A controller verifies that the sensor array is clogged and needs to be cleaned.

In the CA 2 557 549 A1 An analyte detection device is described in which biological particles in a membrane are enriched with a filter. After enrichment, the biological particles are reacted with a visualization reagent and detected via optical devices. Based on a pressure difference between the sides of the membrane, trigger parameters are determined in which the visualization reagent is added to the filtered particles.

The US 5 190 666 A discloses a filter device which filters out biological particles which are then detected, the filter is automatically monitored for a blockage.

The WO 2008/086477 A1 describes a biosensor device having a filter which is characterized by differential pressure sensors, protein sensors, blood sensors, and the like. Ä. Is monitored for constipation or breakage.

In the WO 2005/105276 A2 a filter is described which has a conduction path. In the event of a break in the filter, the resistance of the line path changes, indicating the breakage of the filter.

In general, it is an object of the invention to provide a low-maintenance biosensor device which has a higher reliability than previous biosensor devices.

This object is achieved by a biosensor device having a filter monitoring device.

Advantageous embodiments are the subject of the dependent claims.

Preferably, a biosensor device for detecting biological particles has a detection device for detecting the biological particles present in the sample, wherein the detection device has a filter for collecting biological particles for the purpose of detection. It is particularly advantageous if a filter monitoring device is provided in the biosensor device, which automatically monitors the function of the filter. It is advantageous if this filter monitoring device can detect both a clogging of the filter and a defect of the filter in the form of cracks or breaks and can then output a signal indicating such a dysfunction of the filter.

Advantageously, the filter monitoring device has at least one differential pressure measuring device for measuring a differential pressure across the filter. In this differential pressure measuring device, at least one pressure sensor is preferably provided. It is particularly advantageous if two pressure sensors are provided which can measure the differential pressure across the filter. The two pressure sensors are located in the flow direction of the sample in which the biological particles to be detected are located before and after the filter and indicate the pressure difference between the area in front of the filter and the area after the filter. If an extremely high pressure difference between the two pressure sensors is detected by the differential pressure measuring device, this indicates a blockage of the filter membrane.

Further preferably, the filter monitoring device has at least one flow quantity measuring device for measuring a flow through the filter. This flow rate measuring device can preferably be used to control a flow rate in order to keep it constant. With a clogged filter membrane, the differential pressure between the two pressure sensors would increase at a constant flow rate, whereby a gradual clogging of the filter can be detected.

Advantageously, the filter monitoring device has a voltage measuring device for measuring a mechanical stress on the filter. With such a voltage measuring device, the deflection or the voltage in the filter membrane can be monitored. In the case of micromechanical filters, this is advantageously possible because the voltage measuring device has a piezoelectric element in which piezoresistive sensors or strain gage sensors are integrated. As a result, the pressure sensors can even advantageously be dispensed with, which is advantageous, above all, in the case of miniaturized systems. Cracks in the membrane can be detected because at a predetermined flow rate and differential pressure, the mechanical stresses in the event of a crack change.

Further preferably, the filter monitoring device has a conduction path for establishing an electrical connection on the filter. The conduction path covers the active surface of the filter membrane. If the membrane breaks or gets cracked, the conduction path is also destroyed and loses its conductivity, whereby a defect can be detected on the membrane.

The filter monitoring device preferably has an optical detection unit and a light source on a side of the filter facing away from the optical detection unit. The optical detection unit may be, for example, a photomultiplier. If the filter is illuminated from one side with light from the light source, the optical detection unit located on the opposite side of the filter should not measure an increase in the light intensity measured by the photomultiplier while the filter is intact. Only in the case of a broken filter membrane will more photons pass through the filter and be detected by the photomultiplier. An increase in the measured light intensity indicates a break or tear in the filter membrane.

Advantageously, the filter monitoring device is designed to detect the porosity of the filter. An indication of a defective membrane is the flow resistance that builds up through the filter membrane. This resistance depends, among other things, on the porosity of the filter. Does it come to one Cracking, the porosity increases abruptly and the flow resistance decreases. This increase in porosity can be determined by the ratio of pressure change: flow change: volume change.

Further advantageously, the filter monitoring device is associated with at least one pump for transporting the fluids and / or it is connected thereto. The pump transports the sample and any detection reagents through the biosensor device and in particular through the filter. It is responsible for the flow rate and differential pressure prevailing in the filter area. The flow rate can be kept constant by controlling the pump. With a clogged filter, the flow through the filter is generally hindered, which requires a lot of work by the pump to pump the fluid through the filter. Blockage or incipient blockage of the filter can therefore be detected by monitoring the power consumption or torque of the pump to see if the pump is running at full load.

Therefore, it is advantageous if the filter monitoring device has a load measuring device for measuring the load acting on the pump. As a result, blockages or even partial blockages of the filter or of areas of the fluidics device present in the biosensor device can be detected.

Since the filter monitor is connected to a plurality of sensors for monitoring the filter, it is advantageous if it has a filter monitoring controller which receives and / or processes the signals from the individual components and, depending on the signal, outputs a shutdown command for the biosensor device is trained. If the filter monitoring device detects with the aid of this control device that the filter is clogged or damaged, accurate detection of the biological particles is no longer possible. It is then necessary to maintain the biosensor device either by cleaning the filter (in the event of blockage) or by replacing it (in the event of damage or clogging so severe that it can not be removed).

The filter monitoring control device preferably receives the signals of the differential pressure measuring device and / or the flow rate measuring device and / or the voltage measuring device and / or the line path and / or the optical detection unit and / or the load measuring device. By receiving the signals, therefore, it is capable of outputting a shutdown command and a warning signal indicating that the biosensor device is not functioning as intended, in the event of any degradation of the biosensor device.

If the filter monitoring control device further preferably has an evaluation device for evaluating the signals received by the filter monitoring control device, it is also able to evaluate the received signals and to interpret them correctly. For example, the flow rate through a filter depends on many different parameters. Essential influencing factors are u. a. the filter porosity, the membrane thickness and the applied pressure. By using similar filters (same membrane thickness and porosity), the flow / pressure characteristics of a functioning system with intact filters will be similar. Using a new filter, it is advantageous to first create a flow / pressure characteristic. Since the flow properties of the filter can only deteriorate during operation, a broken membrane can be determined via the history of the flow / pressure characteristic. If a filter membrane is broken, there is a higher flow through the membrane at a lower differential pressure. As a result, one additionally obtains an increased filtered total volume at the same time. An evaluation device can relate these various factors to each other and conclude whether the filter is still functional, whether it is clogged or if it is damaged in any way.

Further preferably, a cleaning device for automatically cleaning the filter is provided. Only by cleaning the filter, it is possible that this can be used several times, and it is advantageous if this cleaning takes place automatically and thus requires the lowest possible maintenance.

Preferably, the filter has a heating device, with the fluids such as cleaning fluids and / or detection fluids such. B. dyes can be tempered locally. Advantageously, the filter for this purpose has at least one heater structure, which particularly preferably comprises a conductor track as Heizmäander, and which can preferably be protected by a passivation layer of SiO ₂ , Al ₂ O ₃ , SiC or diamond-like layers. Advantageously, the temperature measurement is also carried out on the filter, particularly preferably by the heating meander and / or by a separate conductor meander and / or an integrated thermocouple and / or a pn junction.

Since the filter is preferably cleaned by transverse and / or flushing with fluids, advantageously several vessels are provided in the biosensor device in which these fluids are stored. This storage becomes an automatic operation allows the cleaning device, as so, depending on the size of the vessel, rarely the fluids must be filled.

So that at least one of the fluids stored in the plurality of vessels can be used to clean the filter, it is advantageous if this fluid is a cleaning fluid. It can be transported to the filter if at least the vessel in which it is stored, for. B. is connected via a valve with the cleaning device. Preferably, a valve is provided which can select multiple vessels. Thus, depending on the valve position, also different cleaning fluids can be transported to the cleaning device or to the filter. It can thus both several successive cleaning steps are performed with different liquids, but also the cleaning process can be adapted to the requirements depending on the nature of the detected biological particles.

For transporting the cleaning liquid, it is advantageous if the cleaning device has a pump. This pump can pump the cleaning fluid from the vessel in which it is stored to the filter. For a simple construction of the biosensor device, it is advantageous if the pump is not only provided for pumping the cleaning liquid from its vessel to the filter, but can also assume other functions. This includes not only the pumping of all the fluids stored in the several vessels, but also the pumping of the fluid sample. In order to prevent contamination, but also several pumps may be provided in the biosensor device, depending on what needs to meet the biosensor device. If, for example, it is to be transportable and to be able to be integrated into vehicles, it is advantageous if it has the smallest possible dimensions. For fixed use or for use in larger vehicles, it may also be larger in size. Then it is possible to provide several pumps in the biosensor device.

Preferably, the pump is designed such that they both pump the cleaning fluid through the filter, as they can also backwash and / or backwash. That is, the pump should be designed to pump in at least two different directions.

Preferably, the pump of the filter monitoring device is designed as a pump for pumping the cleaning liquid. Thus, the pump can perform several functions, namely to monitor the filter, whether it is clogged or damaged, and at the same time transport the cleaning liquid from the vessel for storage to the filter. Such a construction can save space in the biosensor device.

Preferably, the cleaning liquid is also at the same time a reaction liquid used in the detection of the biological particles in the biosensor device. Also, this space can be saved in the biosensor device, since instead of many vessels, some for cleaning fluids and some for reaction liquids, only a few vessels for storage of selected fluids must be present.

Advantageously, the cleaning fluid is an acid or a base or an alcohol or a detergent. Depending on the type of contamination of the filter, it is advantageous if different functional cleaning fluids can be used. In order to clean the filter as gently as possible, the acid or the base may be a weak acid or a weak base. If this is not enough to clean the filter, it is also possible to use a stronger or stronger acid or a strong base to clean the filter. Organic contaminants are preferably removed by alcohols or detergents. It is also conceivable to carry out several cleaning steps in which different cleaning liquids are rinsed successively over the filter.

A tempering device for tempering the cleaning liquid is advantageously provided. Heating can speed up the cleaning process of the filter. At the same time, however, a cooling of the filter may be necessary if the reaction of the cleaning fluid with the biological material releases heat and thus could attack the filter. The tempering device is preferably designed such that it is optimized for the cleaning process of the filter with the cleaning liquid. Depending on the type of cleaning used, it is advantageous if the liquid used for cleaning can be supplied in tempered form. For this purpose, the detection chamber and / or the measuring chamber z. B. be heated by cartridge heaters. A temperature of the liquid by a hose heating is possible.

Preferably, temperature sensors are provided on the vessels and the filter to avoid overheating and hypothermia. In order to be able to determine the exact temperature of the liquid, a temperature sensor is advantageously introduced directly into the flow. Most preferably, the temperature sensor sits in close proximity to the microfilter. A temperature sensor can also be integrated on the filter. This can be done by implanting a PN diode in a silicon membrane, applying conductors of different materials to a thermocouple to form, or applying a Leiterbahnmäanders that allows in the form of a temperature-dependent change in resistance temperature measurement. The temperature sensors can each be protected by a passivation layer.

Advantageously, a recycling device is provided for the reprocessing of the cleaning liquid. In order to keep the supply of cleaning liquid as low as possible, it makes sense to recycle the cleaning liquid after use. This can be collected in an extra container and cleaned before use by a particle sieve (classic filter).

Preferably, the recycling device has a particle screen and / or activated carbon. Filter and cleaning fluid are advantageously interchangeable after a maximum number of uses. It is also possible first to clean with recycled cleaning liquid and then to clean with a small amount of fresh solution as the last cleaning step.

Advantageously, the cleaning device has a sound generator, in particular an ultrasound unit, or a megasonic unit, for applying sound waves to the filter. The cleaning of silicon wafers and other surfaces by means of megasonic is an established method in the semiconductor and microelectronics industry. So far, however, this technology is used exclusively for cleaning smooth surfaces. Here, however, the use of megasonic for cleaning filters is proposed. Due to the cavitation caused by the cavitation, it is possible to effectively clean filter surfaces. This mechanical cleaning can be additionally supported by the use of detergents. Megasonic is particularly suitable for cleaning smooth filter surfaces, as they occur for example in micromechanical filter or in so-called. Track-etched filter membranes. Depending on the design of the filter elements or of the megasonic transducers, however, deep cleaning is also conceivable. Due to the effective cleaning, a filter element can be recycled, ie reused. Another use of megasonic technology is already conceivable during filtration. On the one hand, air bubbles, which can hinder the filtration, are dissolved and at the same time, particles are prevented from settling. With a suitable choice of megasonic frequency particles of a certain magnitude are set in motion and thereby prevented from settling. Megasound thus supports the filtration process and extends the service life of the filter.

Therefore, the ultrasound unit preferably has a sound generator. The sound generator generates ultrasound (frequency about 20 kHz to 1 GHz), in particular megasonic (frequency about 400 kHz to 4 MHz), with which the filter can be applied for cleaning.

The detection device further preferably has a detection chamber in which the filter is accommodated.

This detection chamber preferably has a separate reactor for pre-staining the sample material. Thus, instead of the process, filtering of the water sample (meaning enrichment of the bacteria on the filter surface), addition of the probes, reaction of the probes with, for example, the bacteria, flushing of unbound probes, detection, staining may also take place in advance in the separate reactor. This can be tempered or temperature controlled. This changes the process to filling with the water sample, addition of the probes, possible mixing and tempering (reaction probes with, for example, bacteria), pumps through the filter (corresponds to accumulation of bacteria on the filter surface), if necessary rinsing, detection. Pre-staining the sample material in the separate reactor can simplify the reaction of the probes with, for example, the bacteria, since easier mixing is possible than if the bacteria are already immobilized on the filter surface.

Advantageously, the detection chamber has a limiting chamber wall. Thus, the range of detection is advantageously separated from the rest of the biosensor device. Contamination of different biosensor device areas can thus be prevented.

The sound generator is advantageously attached to the detection chamber of the detection unit. Thus, the megasonic in the detection chamber or on the filter can be applied.

Further advantageously, at the detection chamber, a nozzle for exiting by megasonic impacted fluid through the chamber wall is arranged in the detection chamber. From the nozzle then enters the acted upon with megasonic fluid on the filter surface and cleans them.

Further advantageously, however, the filter can also be designed as a sound generator. Thus, the microfilter itself is an active element, i. H. it can be designed as an ultrasound generator, in particular as a megasonic generator. This may be particularly advantageous if the biosensor device should be constructed as space-saving.

Advantageously, the filter is then formed from a piezoelectric material or a piezoelectric layer is applied to the filter. In particular, for example, PZT ( Lead zirconate titanate) or AlN (aluminum nitrate) as a piezoelectric layer.

If the filter has electrodes, in particular interdigital electrodes, the piezoelectric material can be advantageously excited.

The piezoelectric material may preferably be protected by a further layer, a passivation layer, from environmental influences, in particular cleaning media.

Furthermore, the geometry of the membrane and the underlying mechanical support structures under the membrane can be adjusted so that the vibration behavior of the membrane is favorable at the selected oscillation frequency.

Immediately after or even during the megasonic cleaning, the fluidic system can be activated to carry out a cross-flow or backwash, thus improving the cleaning procedure.

Further advantageously, the cleaning device has an EHD unit for electrohydrodynamic atomization of the cleaning liquid. Electrohydrodynamic atomization is a process in which a conduit fluid is broken up and dispersed to form a charged nanotube beam. To initiate an EHD beam, electrostatic stress is exerted on the fluid meniscus that exceeds the surface tension that maintains the meniscus intact.

Advantageously, the EHD unit has a capillary for introducing the cleaning liquid from a vessel into the EHD unit, a pressurization for introducing and passing the cleaning liquid into and through the capillary and an electrical contact for generating an electrostatic field at the end of the capillary. In a typical EHD system, a small fluid reservoir stores the conductive process chemical that is to be sprayed, and electrical contact in the reservoir subjects the fluid to potential. A pneumatic control unit applies a controlled pressure to the fluid that is in the reservoir. This results in a flow from the reservoir via a capillary tube into the electrostatic field at the end of the capillary where the fluid is sprayed.

The electrohydrodynamic atomization requires only small volumes of fluid. Use rates may typically be in the range of 0.6 to 2 μl / minute / nozzle. This could significantly save costs when using EHD, as it avoids high volumes of process chemicals and their post-use utilization.

Advantageously, the EHD unit is designed to form nanotubes from the cleaning fluid and / or to act on the filter surface. At the start of the EHD, current flows through the conductive fluid into the capillary. In addition, charged ions migrate in the fluid in opposite directions in the capillary, resulting in an uneven distribution of the charge. Ions of the same polarity as the voltage applied to the reservoir travel to the extremity of the capillary. There, the electrostatic field exceeds the surface tension of the meniscus and results in collapse of the meniscus to form an EHD nanotube beam.

Since the nanodroplets produced by the EHD process are multiply charged, their acceleration can be controlled by the electric field between the exit of the capillary and the object to be cleaned.

Advantageously, the capillary of the EHD unit is arranged in the wall of the detection chamber. Thus, the nanotubes can be applied directly to the filter.

While EHD nanodroplets are very small, they are extremely large compared to ions and ion beams. EHD nanodroplets distribute their energy over a broad area of the target, causing them to simultaneously detach and remove micron and submicron particles. These may be organic films and / or metallic impurities. The energy of an EHD nanodroplet is carried by the large number of nuclei in the nanodroplet. This results in energies below material sputtering limits and prevents direct etching or damage to the surfaces while the contaminant is being removed.

The control of the EHD nanodroplets is implemented electrically by charging the fluid to a certain range where capillary leaks out and is manipulated by the electric field. The speed and size can be changed, resulting in a wide range of process settings, so as to match the nanodroplets to the contaminants and substrate. Nanodroplets can be made to impart an optimal momentum to the particles.

By introducing a microcapillary through the wall of the detection chamber, the filter surface can be cleaned. In this case, a cleaning effect is achieved without introducing high energies, ie the membrane is mechanically stressed very little. Immediately after or even during EHD cleaning, the fluidic system can be activated to carry out a backwash or backwash to improve the cleaning procedure.

Advantageously, the cleaning device has an electrical cleaning device for electrochemical cleaning of the filter. In particular, the cleaning of the filter is carried out by electrophoresis and / or electroosmosis and / or electrolysis.

In electrophoresis or dielectrophoresis, it is possible to pull charged particles away from the filter surface by means of electric fields. In this case, a high electric field is generated at the surface of the filter. Charged dirt particles and bacteria are drawn by the electric field to the opposite polarity electrode and also carry uncharged particles on their way.

Therefore, electrodes for carrying out the electrochemical cleaning methods, in particular as interdigital electrodes, are advantageously formed on the filter. Electrode width and spacing can be z. B. 1 to 10 microns. They can be protected with a passivation layer and also electrically insulated. In this case, the fluidic system can be activated in order to perform cross or backwashing and thus to improve the cleaning procedure. In particular, during backwashing through the filter (by operation of the fluidic system), the particles can be washed away as soon as they are transported across the filter surface by the electrophoresis or dielectrophoresis process and pass through a pore.

Furthermore, the known effect of electroosmosis can be applied (electroosmotic flow in microchannels). Especially at low height of the detection chamber, z. B. 100 to 200 microns, can pump the liquid therein when an electric field is applied across electrodes, which drops across the filter surface. This allows the liquid and with it the particles contained therein to move. The cleaning effect can be increased if an alternating field is applied. This reciprocation corresponds to a mechanical mixing and can be performed at a higher frequency than a constant flow direction reversal in the cross-flushing by the fluidic system with the conventional mechanical pump. In addition, the fluidic system can be activated to perform cross or backflushing to improve the cleaning procedure.

The electrolysis with gas formation (eg of water) can also act as a cleaning of the filter surface. For this purpose, a liquid is split into gases on the filter surface (design as electrode) while supplying electrical voltage. These rising gases dissolve the particles on the filter surface and make it possible to remove the impurities. The counter electrode may be attached to the wall of the detection chamber. When the electrodes are mounted on the filter surface, in particular as interdigital electrodes, an electrode width and an electrode spacing of, for example, 1 to 10 μm are advantageous. Then the required voltage can be minimized, even with electrically poorly conducting electrolytes (eg water).

Preferably, the interdigital electrodes are formed of platinum and / or by screen printing or by vapor deposition or sputtering. This makes the electrodes particularly robust, since platinum is a precious metal.

Preferably, the cleaning device has at least one cleaning control device. Thus, the cleaning process or the various cleaning processes is controlled and adapted to the contamination by certain biological particles.

Therefore, it is advantageous if the cleaning control device is designed to activate and deactivate the ultrasound unit and / or the EHD unit and / or the electrochemical cleaning and / or the pump. The cleaning control device can thus start all cleaning processes at the same time, or they start one after the other or in a selected combination. By controlling the pump, it is possible, even during a cleaning step with, for example, ultrasound or electrohydrodynamic atomization to rinse the filter with cleaning fluid, so as to improve the cleaning yet.

Advantageously, the cleaning control device is activated by the filter monitoring control device. If the filter monitoring controller indicates contamination of the filter, it is advantageous if the filter can then be cleaned immediately. Therefore, it is advantageous if the cleaning by the cleaning control device is started immediately after detecting an impurity.

In order for the biosensor device to be operated automatically, it is advantageous if a sampling device is provided which in particular can receive fluid sample material directly from a line.

It is advantageous if the sampling device has a diverting / passage device, which can permanently discharge the sample material from the line and at the same time Sample material can pass permanently through the sampling device.

Advantageously, the sample material is introduced into the sampling device via a bypass connected to the line, flows back into the line tangentially to the filter through the detection chamber and via a multi-way valve.

It is advantageous if the bypass has a switchable pressure reducer, which keeps the flow of the sample material through the sampling device and the detection chamber constant or prohibits the flow during a measurement.

By such a device, a permanent flow is generated. In the implementation with permanent flow of a part of, for example, drinking water from the supply line is passed into a bypass. A switchable pressure reducer reduces the pressure and simultaneously the flow rate in this bypass. Is the Fluidikeinrichtung active, so a constant flow of, for example, drinking water is passed through the bypass, flows through the detection chamber tangentially and is added via a multi-way valve back to the drinking water pipe. The flow through the bypass is permanent. There can be no residues left in the pipes. During a measurement, the pressure reducer prohibits the flow from the supply line. After the measurement, the pressure reducer opens again and the flow through the bypass is released.

By such a construction, the sampling device is connected to the fluidic device with the detection chamber. Thus, the fluid sample, for example, drinking water can be introduced without detours in the detection chamber, where then a reliable measurement of exposure to biological particles can be performed.

Advantageously, an air bubble sensor for detecting air bubbles is provided in the fluidic device. Air bubbles are troublesome, especially if the detection of biological particles is to be on a quantitative basis. If air bubbles are present in a sample, then it is no longer possible to deduce the concentration in the volume. Therefore, it is advantageous if the presence of air bubbles is detected via an air bubble sensor, and a message is issued that air bubbles are present. Thus, these can advantageously be removed from the biosensor device before the detection of the biological particles takes place.

In order to prevent contaminations of the fluid sample, for example a water sample, it is advantageous if the sampling device has a switching valve which distinguishes between two operating modes of the biosensor device. In a first position, the switching valve directs the sample material to the fluidics device while directing it past the fluidic device in a second position. As a result, a direct sampling of the example drinking water pipe is possible, and there are no pipes with stagnant water in which biological particles can be concentrated over time. Such concentration could lead to a falsified measurement result. Furthermore, by means of such a setting, all connections between, for example, the drinking water line and the filter can be kept germ-free.

Advantageously, the sampling device has a rotating device which has at least one passage and at least one receiving position for the filter. Such a rotating device may be formed such that it can be screwed directly into the example drinking water line.

Advantageously, it can be screwed into at least two positions in the line, in a first position while the filter is screwed into the drinking water pipe, and in a second position of the passage. With such a construction, the filter can be introduced directly into the sample of interest, without any lines in between, in which contaminations and thus falsifying results can form.

In order to enable a permanent flow through the drinking water pipe, for example, it is advantageous if the rotating device also has a passage which is screwed into the drinking water line when no filter for sample intake in the drinking water pipe is currently available.

Advantageously, a safety device is provided which prevents contamination of the line in the event of a malfunction of the biosensor device. Such a safety device should preferably be designed such that it prevents backflow of the sample already taken into the line.

This is advantageously achieved in that the safety device is a check valve. With such a check valve in the line, the already taken sample can no longer retreat into the drinking water pipe. If there is a technical problem in the biosensor device, then no detection and / or cleaning fluids from the biosensor device can enter into the drinking water line.

To avoid cracks in the filter or to increase its service life, it is advantageous if a high differential pressure is prevented. This differential pressure is caused by the Differential pressure measuring device monitors. Since pressure fluctuations should not occur abruptly but as slowly as possible, it is advantageous if the pump is controlled by the differential pressure measuring device. Thus, the pressure fluctuations in the system are gentle. In particular, in micromechanical filters made of relatively brittle materials, eg. As silicon, this leads to improvements.

In the following the invention will be explained in more detail with reference to the accompanying drawings. Showing:

1 an overview of a biosensor device;

2 an overview of a sampling device of the biosensor device;

3 the function of a switching valve in the sampling device during normal operation of the biosensor device;

4 the function of the switching valve of the sampling device in the detection;

5 the retraction of a membrane filter into a conduit in which a sample of interest flows and the subsequent detection of the biological particles present on the membrane filter.

1 shows a whole with the reference numerals 10 designated biosensor device for the detection of biological particles. The biosensor device 10 has a detection device 12 on that a filter 14 for collecting biological particles for detection.

In the DE 10 2006 026 559 A1 , of the DE 10 2007 021 387 A1 and the unpublished patent application DE 10 2008 035 772 is described as such, in particular micromechanical filter 14 can be used for the detection of particles, in particular of bacteria. The use of the micromechanical filter 14 is hereby incorporated into this application with respect to these three disclosures. These so-called microfilters consist of a thin, z. B. 1 micron thick membrane, z. B. of monocrystalline silicon or possibly of diamond or with. Diamond coating. The membrane is perforated, the holes have a diameter of z. B. 450 nm, ie the membrane or the microfilter forms a sieve. You pump z. B. a water sample through the filter 14 , bacteria (eg 1 μm in diameter) are retained on the filter surface where they can subsequently be detected. These microfilters are integrated into an overall system, including fluidics, optics, electronics, creating a biosensor system that can be used in particular for the detection of bacteria in water. However, other biological particles such as spores, fungi, etc., can be detected. In addition to water, other fluids, such. As air, are analyzed.

A fluidic device 16 passes a fluid sample over the filter 14 , The filter 14 is as a filter membrane 18 designed to hold back the bacteria on the filter 14 can no longer guarantee if there is a rupture of the filter membrane 18 comes. Therefore, there must be damage to the filter 14 be ascertained in all circumstances.

To cracks in the filter 14 To avoid or increase its life, too high a differential pressure between a first range 20 in front of the filter 14 and a second area 22 after the filter 14 be prevented. In addition, pressure fluctuations should not be abrupt, but slow. Therefore, a pump 24 passing the sample through the fluidics device 16 to the filter 14 pumps, via a differential pressure measuring device 26 regulated. The differential pressure measuring device has two pressure sensors in the embodiment shown 28 . 30 on. The first pressure sensor 28 is for measuring the pressure in the first area 20 in front of the filter 14 configured while the second pressure sensor 30 for measuring the pressure in the second area 22 after the filter 14 is designed. The differential pressure measuring device 26 forms a first part of a filter monitoring device 32 to monitor the filter 14 is designed.

Regarding the filter membrane 18 During operation, two possible errors may occur: The filter membrane 18 is clogged or the filter membrane 18 is damaged.

The filter monitoring device 32 points next to the differential pressure measuring device 26 further a flow quantity measuring device 34 on. This is for measuring the flow rate through the filter 14 designed, and has a flow sensor 36 on. The monitoring of the filter 14 can be done by simultaneously measuring the flow rate and the differential pressure. This can be done by another parameter, for example the flow of the pump 24 or their power consumption or their torque to be supplemented. This can be z. As blockages or partial blockages of the filter 14 or areas of the fluidic device 16 detect. By by regulating the pump 24 constant flow rate would z. B. increase the differential pressure with increasing constipation.

The clogging of the filter membrane 18 For example, when drinking water is analyzed, it depends on the water quality of the water under investigation and the effectiveness of cleaning. Include that too Examining water numerous particles, is a blockage of the filter 14 likely.

• 1. Die beiden Drucksensoren 28, 30 zeigen extrem hohen Differenzdruck an.
• 2. Der Flusssensor 36 zeigt keinen oder nur einen geringen Fluss an.
• 3. Eine Lastmesseinrichtung 38, die zur Messung der auf die Pumpe 24 wirkenden Last ausgebildet ist, zeigt an, dass die Pumpe 24 auf Volllast steht.
• 4. Eine in der Filterüberwachungseinrichtung 32 implementierte Filterüberwachungssteuerungseinrichtung 40, die zum Empfangen und/oder Verarbeiten von Signalen ausgebildet ist, und eine Auswerteeinrichtung 42 zum Auswerten der empfangenen Signale aufweist, kann eine Fluss-/Druckcharakteristik nicht aktualisieren oder auswerten.

If there is a blockage of the filter membrane 18 , this can be stated as follows:
A tangential flow across the filter surface works properly. When flowing through the filter membrane 18 at least one of the following disturbances occurs:

• 1. The two pressure sensors 28 . 30 indicate extremely high differential pressure.
• 2. The flow sensor 36 indicates little or no flow.
• 3. A load measuring device 38 for measuring the pump 24 acting load is formed, indicates that the pump 24 is on full load.
• 4. One in the filter monitor 32 implemented filter monitoring control device 40 , which is designed for receiving and / or processing of signals, and an evaluation device 42 for evaluating the received signals, a flow / pressure characteristic can not update or evaluate.

Damage to the filter membrane 18 can be determined as follows:
The most preferred way, a crack in the filter membrane 18 It is, sensors, on the surface or in the filter membrane 18 provided. In a preferred embodiment, these are conduction paths 44 containing the active surface of the filter membrane 18 cover. Indicates the filter membrane 18 a break on, are also the conduction paths 44 destroys and loses its conductivity.

Preferably, to detect a cracked filter membrane 18 an optical detection unit 46 provided that the number of photons coming from a Lichquelle 48 go out, counts. The light source 48 is in front of the first area 20 in front of the filter 14 arranged while the optical detection unit 46 with the second area 22 after the filter 14 located. Will the light passing through the filter membrane 18 appears with, for example, a photomultiplier of the optical detection unit 46 measured, an increase in light intensity should never be detected when the filter 14 is intact. Only in case of a crack of the filter membrane 18 takes the from the optical detection unit 46 measured light intensity too.

Furthermore, the flow rate depends on the filter 14 from many different parameters. Significant influencing factors include the filter porosity, the thickness of the filter membrane 18 and the applied pressure.

Another indication of a defective filter membrane 18 is the flow resistance passing through the filter membrane 18 is built. This resistance depends, among other things, on the porosity of the filter 14 from. If cracking occurs, the porosity increases abruptly and the flow resistance decreases. The increase in porosity is detected in the preferred embodiment via the change in the flow rate or the differential pressure.

The filter monitoring device 32 further includes a voltage measuring device 52 which is used to measure a mechanical stress on the filter 14 is trained. It measures the deflection or the stresses in the filter membrane 18 , For micromechanical filters 14 this is possible by integration of piezoelectric elements 54 or strain gage sensors, which cause cracks in the filter membrane 18 show an altered mechanical tension.

A big influence on the stability of the filter membrane 18 has the material used. This is characterized by the material constants elasticity modulus, Poisson's ratio, ie transverse contraction number, and tensile strength, wherein the breaking strength of the filter membrane 18 primarily on the thickness of the filter membrane 18 depends. Another influencing factor is the aspect ratio of the filter membrane 18 , Optimum stability values are obtained with an aspect ratio of 1 to 1. A microfilter usually always consists of the filter membrane 18 and a back support structure. Because the filter membrane 18 connected to the support structure, this causes the dimension of the active filter surface and thus the aspect ratio of the membrane. Dissolve the filter membrane 18 From the support structure, one has the opportunity, by a suitable design of the front, ie the filter membrane 18 , the aspect ratio of the filter membrane 18 regardless of the support structure. Thus one can optimize the stability values.

At the same time, by adjusting the back side, i. H. the support structure, improved flow characteristics are realized.

The filter monitoring controller 40 is for receiving signals from both the differential pressure measuring device 26 , as well as signals of the flow quantity measuring device 34 , the voltage measuring device 52 , the leadership path 44 , the optical detection unit 46 and the load-measuring device 38 educated. Evaluates the evaluation device 42 an erroneous signal in one of the aforementioned components is the filter monitoring control means 40 for issuing a shutdown command for the biosensor device 10 designed.

Apart from the detection of only low bacterial concentrations, the sensor information of the system, ie pressure, flow rate, load, etc., can be used to evaluate the detection signal in the optical detection unit 46 be used. An alarm signal due to bacterial contamination of the water may, for. B. are suppressed when the sensors are not a certain occupancy of the filter 14 Show. The bacteria must eventually lead to contamination. If this is not recognizable, it may be due to an error in the optical detection unit 46 or in the marking process. This test can be used especially if the medium to be analyzed is low in particles.

The sensor information of the filter monitoring device 32 deliver on determination of clogging of the filter 14 Information about the particle load of the medium to be analyzed. This information can be further processed to z. B. to give a warning.

Particles in the medium to be examined are troublesome, among other things because they limit the possible amount of sample to be filtered. A prefiltration to remove large particles is sometimes not desirable because z. B. bacteria in biofilms attached to larger particles and retained by the prefiltration and thus could not be detected. One way to analyze larger volumes despite particles and yet eliminate any possible bacteria is to use two or more filters 14 to use different pore diameter. In particular, z. For example, in the case of drinking water, the sample through a filter 14 be pumped with 1.5 micron pore size. That's the filter 14 passing medium is replaced by another filter 14 pumped with 450 nm pore size. On both filters 14 the detection takes place. The analyzable sample volume is larger than when using only one filter 14 with 450 nm pore size, as in the proposed method, the pore size of the first filter 14 is significantly larger and the sample for the second filter 14 is prepared by the first one. By moving on a linear stage, it is possible to inexpensively, without the need for a further optical system, both filters 14 analyze.

The detection of biologically relevant particles can be done by luminescence instead of fluorescence. As a result, noise effects such as self-fluorescence of particles can be minimized.

Instead of detection by a photomultiplier or the like for measuring the total intensity, with an imaging method, for. As a CCD camera, and the surface of the filter 14 be imaged. For this purpose, an optical system for enlarging the image of the filter surface can be used. Through data and image processing, an automatic detection of the target organisms can take place.

In the preferred embodiment, the filter is located 14 in a detection chamber 56 passing through a chamber wall 58 is limited to the environment. The detection chamber 56 can be tempered, in particular, it can be heated. The temperature can thus be monitored or regulated.

To the filter membrane 18 After an analysis to be able to use in full goodness, an effective cleaning procedure should be found. There should be no bacteria or dirt left on the filter surface.

Therefore, in the preferred embodiment, a cleaning device 60 for automatic cleaning of the filter 14 intended. The cleaning device 60 has several vessels 62 for storing fluids. Among other things, in the vessels 62 also stored the cleaning fluids used to clean the filter 14 needed. The cleaning device 60 is over a valve 64 with the vessels 62 connected. The valve 64 is designed such that it has different vessels 62 select separately from each other and with the cleaning device 60 can connect. The pump 24 pumps the selected fluid out of the vessel 62 to the filter 14 , It is designed so that it not only the fluid to the filter 14 can pump down, but the selected fluid, such as the cleaning fluid, also on the filter 14 back and / and can rinse.

The cleaning fluid flows through a flow system 66 that of a four-way double-selection valve 68 is controlled. This directs that from the pump 24 pumped fluid either via one of the pressure sensors 28 . 30 on the filter 14 , or in a trash 70 ,

In order to keep the supply of cleaning liquid as low as possible, it makes sense to the cleaning liquid in a recycling facility 71 to recycle. That means cleaning fluid after cleaning the filter 14 , back to the four-way double-selection valve 68 flows, is collected in an extra container, here the waste 70 , In this there is a particle screen, in which the cleaning fluid can be cleaned. In addition, activated carbon is present in the container.

In the preferred embodiment, the liquid used for cleaning is supplied in tempered form. This is in the cleaning device 60 a tempering device 72 provided for tempering the cleaning fluid.

To avoid overheating and hypothermia, the tempering device 72 therefore a first temperature sensor 74 on the vessels 62 and a second temperature sensor 76 on the filter 14 on.

For even better cleaning of the filter 14 has the cleaning device 60 furthermore a sound generator, preferably an ultrasound unit 78 preferably a megasonic unit 80 for applying megasonic to the filter 14 on. With this sound generator 82 Megasound is generated which causes cavitation, with which it is possible to effectively clean the filter surface.

In addition, the filter is also 14 as a sound generator 82 educated. It is formed of a piezoelectric material and has electrodes configured as interdigital electrodes for exciting the piezoelectric material. A passivation layer 88 protects the piezoelectric material from external influences that could destroy it.

For even better cleaning, the cleaning device 60 an EHD unit 90 on, which performs an electrohydrodynamic atomization of the cleaning liquid and thus the filter 14 cleans. The EHD unit 90 has a capillary 92 put on the cleaning fluid from one of the vessels 62 into the EHD unit 90 passes. By applying pressure to the cleaning fluid, this is in the capillary 92 introduced and passed through it and into an electrostatic field 94 at the end of the capillary 92 introduced by an electrical contact 96 is produced. From the cleaning liquid, nanotubes form on the filter 14 be charged, and the filter 14 thus clean.

For an even better cleaning effect of the cleaning device 60 are to achieve electrochemical cleaning equipment for electrochemical cleaning of the filter 14 intended. The electrochemical cleaning device 100 is designed to carry out electrophoresis or electroosmosis or electrolysis. It has electrodes 102 on, in a special embodiment on the filter 14 are formed as interdigital electrodes. The interdigital electrodes are made of platinum, since this is particularly resistant to external influences.

To the various cleaning options of the cleaning device 60 to control is a cleaning control device 104 provided that can activate and deactivate the individual cleaning processes. You can z. B. simultaneously the ultrasonic unit and the pump 14 activate while the EHD unit 90 and the electrochemical cleaning device 100 are disabled. Other combinations of cleaning are possible.

The cleaning control device 104 is via the filter monitoring controller 40 activated. When the filter monitoring controller 40 has recognized that the filter 14 requires cleaning, z. B. because it is clogged, it gives a signal to the cleaning control device 104 , which then starts the corresponding cleaning processes. Upon detection in the biosensor device 10 as well as during cleaning, bubbles in the cleaning fluid have a negative effect. Therefore, in the fluidic device 16 an air bubble sensor 106 provided that detects the occurrence of bubbles and outputs a message, so that these bubbles can be removed.

The biosensor device 10 is for taking a sample from the water line through the sampling device 108 educated. This is designed such that it can take sample material directly from a line, and has for this purpose preferably a pressure reducer 110 on.

2 shows an overview in which the sampling device 108 is shown. It has a bypass 112 on, the discharge of the sample, here the drinking water, directly from the line 114 makes possible. The sampling device has a diverting / passing device 116 on, the permanent sample material from the line 114 into the biosensor device 10 rejects them. At the same time, it permanently passes sample material through the sampling device 108 into the detection chamber 56 and through a multiway valve 118 , From this multi-way valve 118 The discharged water can either be returned to the line 114 be returned or the waste 70 be supplied. The bypass 112 indicates the pressure reducer 110 which is switchable and which may be switched to either flow the sample material through the sampling device 108 keeps constant, or forbids the river. This is especially the case when in the detection chamber 56 a measurement is performed. A flow of sample material through the detection chamber 56 This would only interfere, which is why the river must be prohibited during this time. In the detection, it is advantageous that the detection chamber 56 a separate reactor 120 in which the sample material is pre-dyed. This simplifies the reaction of the probes with the bacteria, and faster detection on the filter membrane 18 is possible. The sampling device 108 is about the Fluidikeinrichtung 16 with the detection chamber 56 connected. About the fluidic device 16 can the reaction liquids from the vessels 62 by means of the valve 64 into the detection chamber 56 be introduced. An additional pump 122 is for pumping out the sample material from the detection chamber 56 in the trash 70 intended. After a measurement, a certain flushing volume must be via the multiway valve 118 in the trash 70 be routed to prevent contamination of the drinking water with process fluids.

The 3 and 4 show a preferred embodiment in which the supply line to the biosensor device 10 is cleanable. According to the Drinking Water Ordinance or according to DIN EN ISO 19458 it is envisaged that the water sample should be as direct as possible to the analysis element, ie to the filter 14 should come to avoid contamination by germs that are not present in the actual sample but in, for example, the hoses. All sampling containers must be germ-free. A first way to prevent contamination is in the 3 and 4 shown. On-off valve 124 becomes in normal operation of the biosensor device 10 who in 3 is shown, switched such that the sample material at the Fluidikeinrichtung 16 and thus at the detection chamber 56 is bypassed. At the same time, the biosensor device 10 and in particular the fluidics device 16 be kept germ-free by means of suitable disinfectants. For a sample taken in 4 is shown, the switching valve 124 switched such that the sample material of Fluidikeinrichtung 16 and thus the detection chamber 56 is forwarded. The sample material flows through previously disinfected fluidic elements before it reaches the filter.

Like the filter 14 directly into a line through which the sample flows 126 can be introduced is in 5 shown in four steps. In this case, the sampling device 108 a rotating device 128 on. This has four different positions, by turning the rotator 128 into the pipe 126 can be introduced. In the first step 130 becomes a recording position for the filter 14 into the pipe 126 screwed. This is the filter 14 directly in the drinking water stream and can trap biological particles. With the further steps 132 to 136 becomes the filter 14 turned to different positions, where various processes can take place, such as the visualization of the bacteria in step 132 , the detection step in step 134 and the washing step in step 136 ,

The turning device 128 is designed to suit each of these steps 130 to 136 a passage 138 that at the position of the rotating device 128 into the pipe 126 is screwed in. This ensures a permanent, undisturbed flow of drinking water.

To avoid that in case of failure of the biosensor device 10 Drinking water in the pipe 114 is contaminated by, for example, reaction liquids or the like, a safety device in the form of a check valve is provided. Thus, no already derived water back into the pipe 114 flow and contaminate the drinking water.

The biosensor device 10 and their components are thermally insulated and have temperature sensors 74 . 76 for controlling the temperature of the cleaning and reaction liquids. All fluids and the overall system and components in the biosensor device 10 , as well as the detection chamber 56 and all leads are tempered.

In the detection chamber, a sample can be examined after the sample has been taken from a water pipe, with a pressure reducer if required 110 is used. Particularly advantageous is the presence of a check valve, which prevents contamination of the drinking water in case of failure.

The overall system is monitored by measuring the pressure difference across the filter 14 , in particular via two pressure sensors 28 that are in the detection chamber 56 are integrated. As a result, measurement errors are caused by a pressure drop between the filter surface and the measuring point outside the detection chamber 56 avoided.

The system continues via the flow sensor 36 that after the pump 24 switched, monitored.

Everywhere in the biosensor device 10 , in the housing, in the detection chamber 56 , in the fluidic system 16 Temperature sensors are available that allow for optimal temperature control of reagents, media and components and avoid overheating and too low a temperature.

Werter is an air bubble sensor 106 provided, the bubbles in the Fluidikeinrichtung 16 recognize and report.

LIST OF REFERENCE NUMBERS

10

biosensor

12

detection device

14

filter

16

fluidic

18

filter membrane

20

first area

22

second area

24

pump

26

Differential pressure measuring device

28

first pressure sensor

30

second pressure sensor

32

Filter monitoring device

34

Flow rate measuring device

36

flow sensor

40

Filter monitoring control device

42

evaluation

44

conduction paths

46

optical detection unit

48

light source

52

Voltage measuring device

54

piezoelectric elements

56

detection chamber

58

chamber wall

60

cleaning device

62

vessels

64

Valve

66

river system

68

Four-way double valve selection

70

waste

71

recycling facility

72

tempering

74

first temperature sensor

76

second temperature sensor

78

ultrasound unit

80

Megasonic unit

82

sound generator

88

passivation

90

EHD unit

92

capillary

94

electrostatic field

96

electric contact

100

Electrochemistry cleaning device

104

Cleaning control device

106

Bubble sensor

108

Sampling device

110

pressure reducer

112

bypass

114

management

116

Ausleit- / Durchleitvorrichtung

118

Multi-way valve

120

reactor

122

pump

124

switching valve

126

management

128

rotator

130

Step 1

132

step 2

134

step 3

136

Step 4

138

passage

Claims (15)

Biosensor device ( 10 ) for the detection of biological particles with a detection device ( 12 ) for detecting the biological particles present in the sample, wherein the detection device ( 12 ) a filter ( 14 ) for collecting biological particles for detection, wherein a filter monitoring device ( 32 ) with a voltage measuring device ( 52 ) for measuring a mechanical stress on the filter ( 14 ) for automatically monitoring the function of the filter ( 14 ) is provided. Biosensor device ( 10 ) according to claim 1, characterized in that the filter monitoring device ( 32 ) at least one differential pressure measuring device ( 26 ) for measuring a differential pressure across the filter ( 14 ) and / or at least one flow quantity measuring device ( 34 ) for measuring a flow through the filter ( 14 ), wherein preferably the voltage measuring device ( 52 ) a piezoelectric element ( 54 ) and / or wherein preferably the filter monitoring device ( 32 ) a conduction path ( 44 ) for producing a conductivity on the filter ( 14 ) and / or an optical detection unit ( 46 ) and a light source ( 48 ) on one of the optical detection unit ( 46 ) facing away from the filter ( 14 ) and / or for detecting the porosity of the filter ( 14 ) and / or at least one pump ( 24 ) is assigned for transporting fluids and / or with the pump ( 24 ) and / or a load measuring device ( 38 ) for measuring the pump ( 24 ) has acting load. Biosensor device ( 10 ) according to claim 2, characterized in that the filter monitoring device ( 32 ) a filter monitoring control device ( 40 ) for receiving and / or processing signals and / or for outputting a shutdown command for the biosensor device ( 10 ) and / or that the filter monitoring control device ( 40 ) for receiving signals of the differential pressure measuring device ( 26 ) and / or the flow quantity measuring device ( 34 ) and / or the voltage measuring device ( 52 ) and / or the management path ( 44 ) and / or the optical detection unit ( 46 ) and / or the load measuring device ( 38 ) is formed and / or at least one evaluation device ( 42 ) for evaluating the filter monitoring control device ( 40 ) received signals Biosensor device ( 10 ) according to one of the preceding claims, characterized in that a cleaning device ( 60 ) for automatically cleaning the filter ( 14 ) is provided. Biosensor device ( 10 ) according to claim 4, characterized in that a plurality of vessels ( 62 ) are provided for storing fluids, in particular for storing a cleaning liquid, and / or that at least one vessel ( 62 ) for storing Fluids via a valve ( 64 ) with the cleaning device ( 60 ) connected is. Biosensor device ( 10 ) according to claim 5, characterized in that the cleaning device ( 60 ) a pump ( 24 ) for pumping the cleaning liquid from the at least one vessel ( 62 ) to the filter ( 14 ) and / or that the pump ( 24 ) for back and forth flushing of the cleaning liquid through the filter ( 14 ) and / or the pump ( 24 ) of the filter monitoring device ( 32 ) as a pump ( 24 ) is designed for pumping the cleaning liquid Biosensor device ( 10 ) according to one of claims 5 or 6, characterized in that the cleaning liquid comprises a reaction liquid for use in the detection of biological particles in the biosensor device ( 10 ) and / or an acid or a base or an alcohol or a detergent and / or that a tempering device ( 72 ) for tempering the cleaning fluid and / or to prevent overheating and hypothermia temperature sensors ( 74 . 76 ) on the vessels ( 62 ) and the filter ( 14 ) are provided. Biosensor device ( 10 ) according to one of claims 5 to 7, characterized in that a recycling device ( 71 ) is provided for cleaning the cleaning liquid and / or that the recycling device ( 71 ) has a particle screen and / or activated carbon. Biosensor device ( 10 ) according to one of claims 4 to 8, characterized in that the cleaning device ( 60 ) an ultrasound unit ( 78 ), in particular a megasonic unit ( 80 ), with a sound generator ( 82 ) for applying the filter ( 14 ) with sound waves and / or that the detection device ( 12 ) one the filter and / or a separate reactor ( 120 ) for pre-staining the sample material and / or a limiting chamber wall ( 58 ) having detection chamber ( 56 ) and / or that the sound generator ( 82 ) at the detection chamber ( 56 ) of the detection device ( 12 ) and / or that a nozzle for the escape of megasonic-loaded fluid through the chamber wall ( 58 ) into the detection chamber ( 56 ) at the detection chamber ( 56 ) and / or the filter ( 14 ) as a sound generator ( 82 ) and / or is formed from a piezoelectric material or comprises a layer of piezoelectric material, in particular of PZT or AlN, and / or electrodes, in particular interdigital electrodes, for exciting the piezoelectric material and / or a passivation layer (US Pat. 88 ) for protecting the piezoelectric material. Biosensor device ( 10 ) according to one of claims 4 to 9, characterized in that the cleaning device ( 60 ) an EHD unit ( 90 ) for electrohydrodynamic atomization of the cleaning liquid and / or that the EHD unit ( 90 ) a capillary ( 92 ) for introducing the cleaning liquid from a vessel ( 62 ) into the EHD unit ( 90 ), a pressurization for introducing and passing the cleaning liquid into and through the capillary ( 92 ) and an electrical contact ( 96 ) for generating an electrostatic field ( 94 ) at the end of the capillary ( 92 ) and / or that the EHD unit ( 90 ) is formed to form nanodroplets from the cleaning fluid and / or to act upon the filter surface and / or that the capillaries ( 92 ) of the EHD unit ( 90 ) in the chamber wall ( 58 ) of the detection chamber ( 56 ) is arranged. Biosensor device ( 10 ) according to one of claims 4 to 10, characterized in that the cleaning device ( 60 ) an electrochemical device ( 100 ) for electrochemical cleaning of the filter ( 14 ), in particular by means of electrophoresis and / or electroosmosis and / or electrolysis, and / or that electrodes for carrying out the electrochemical purification processes on the filter ( 14 ), in particular as interdigital electrodes and / or made of platinum and / or by screen printing or by vapor deposition or sputtering. Biosensor device ( 10 ) according to one of claims 9, 10 or 11, characterized in that the cleaning device ( 60 ) at least one cleaning control device ( 104 ) and / or that the cleaning control device ( 104 ) for activating and deactivating the ultrasound unit ( 78 ) and / or the EHD unit ( 90 ) and / or the electrochemical cleaning and / or the pump ( 24 ) and / or that the cleaning control device ( 104 ) by the filter monitoring control device ( 40 ) is activated. Biosensor device ( 10 ) according to one of claims 9 to 12, characterized in that a sampling device ( 108 ) is provided for receiving, in particular fluid, sample material directly from a line ( 114 ) and / or that the sampling device ( 108 ) a diversion / transit device ( 116 ) for permanent discharge of the sample material from the line ( 114 ) and for the permanent passage of the sample material through the sampling device ( 108 ) and / or that the sample material via a to the line ( 114 ) connected bypass ( 112 ) into the sampling device ( 108 ) flows, the detection chamber ( 56 ) flows tangentially and via a multi-way valve ( 118 ) back into the line ( 114 ) and / or that the bypass ( 112 ) a switchable pressure reducer ( 110 ), the flow of the sample material through the Sampling device ( 108 ) and the detection chamber ( 56 ) and prevents the flow during a measurement. Biosensor device ( 10 ) according to claim 13, characterized in that the sampling device ( 108 ) with the fluidic device ( 16 ) for establishing a connection between the sampling device ( 108 ) and detection chamber ( 56 ) and / or a switching valve ( 124 ) having the sample material in a first position of the fluidic device ( 16 ) and in a second position the sample material at the fluidic device ( 16 ) and / or a rotating device ( 128 ), wherein the rotating device ( 128 ) with at least one passage ( 138 ) and at least one receiving position for at least one filter ( 14 ) is formed and / or that the rotating device ( 128 ) in at least two positions in the line ( 126 ), wherein the at least one filter ( 14 ) in a first position in the line ( 126 ) and in a second position the at least one passage ( 138 ) in the line ( 126 ) is positioned. Biosensor device ( 10 ) according to claim 14, characterized in that at least one air bubble sensor ( 106 ) in the fluidic device ( 16 ) for the detection of air bubbles and for issuing a message and / or a safety device ( 140 ), which is a contamination of the line ( 114 ) in case of failure and / or that a check valve ( 142 ) is provided, the safety device ( 140 ) and / or that the at least one differential pressure measuring device ( 26 ) for controlling the pump ( 24 ) is trained.

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