WO2011042254A1

WO2011042254A1 - Biosensor device comprising a filter monitoring unit

Info

Publication number: WO2011042254A1
Application number: PCT/EP2010/062507
Authority: WO
Inventors: Andreas Helwig; Christoph Heller; Ulrich Reidt; Alois Friedberger; Eberhard Rose
Original assignee: Eads Deutschland Gmbh
Priority date: 2009-10-08
Filing date: 2010-08-26
Publication date: 2011-04-14
Also published as: DE102009048790A1; DE102009048790B4

Abstract

A biosensor device (10) comprises a filter monitoring unit (32) for the automatic monitoring of the function of a filter (14) present in a biosensor device (10). Said filter monitoring unit (32) comprises a plurality of sensors which monitor the differential pressure across the filter (14), the flow quantity through the filter (14), the mechanical stress on the filter (14) and other parameters. If the filter monitoring unit (32) detects a clogging of the filter, it activates a cleaning unit (60) which cleans the filter (14). If it detects damages to the filter (14), it outputs a signal indicating that maintenance is required.

Description

Biosensor device with filter monitoring device

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 for collection and collection

Concentrating the biological particles is formed. 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. This clogging makes the filter in

worst case already unusable after further use for further detection. Examples of biosensor devices for the detection of biological particles which comprise a membrane filter for filtering out biological particles for the purpose of detection are found, for example, in WO2005 / 102528A1 and WO03 / 005013A1. As described in US5726026 and US2006 / 0257941A1, the problem of the clogged filter is solved in that it is discarded after performing the detection step. So will a contamination between

consecutive samples are prevented and the functionality of the filter is guaranteed 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

for example, has bumps.

According to the non-prepublished German patent application DE 10 2008 035 772.3, to which reference is expressly made for further details, is

proposed to manufacture such a resistant filter made of diamond. However, such filters are too expensive to accept after each detection step

to dispose.

Therefore, there is a desire that the filter can be cleaned in order to use it again. A detection device which describes the possibility of cleaning the filter in order to reuse it is disclosed in WO2008 / 135452A2. 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.

A routine cleaning of the filter, even if it after each

Detection test is performed, but does not guarantee the full functionality of the thus prepared filter. 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 by the regular Cleaning process is completely freed from the adding biological particles, 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.

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

Has biosensor devices.

This object is achieved by a biosensor device having a

Having 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 is preferably at least one

Pressure sensor 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 in the flow direction of the sample in which the biological particles to be detected are present, 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 may preferably for controlling a

Flow rate can be used 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 micromechanical filters, this is advantageously possible because the voltage measuring device is a piezoelectric

Has element integrated in the piezoresistive sensors or strain gauge sensors. 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.

Preferably, the filter monitoring device 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 can, for example, a

Be a photomultiplier. If the filter is from one side with light from the light source illuminated, the optical detection unit, which is located on the

is located on the opposite side of the filter, no increase in light intensity, which is measured by the photomultiplier measure, as long as 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 thus indicates a break or crack in the

Filter membrane on.

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 u. a. from the porosity of the filter. If cracking occurs, 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 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 monitoring device is connected to several sensors for monitoring the filter, it is advantageous if they have one

Filter monitoring control device has, which receives the signals from the individual components and / or processed and, depending on the signal, for outputting a shutdown command for the biosensor device is formed. Should the

Filter monitoring device using this control device recognize that the filter is clogged or damaged, is an accurate detection of

biological particles are no longer possible. It is then necessary that the

Biosensor device is maintained by either the filter is cleaned (in case of clogging) or replaced (in case of damage or in such a strong blockage 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 quantity 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, it is therefore capable of any impairment of the

Biosensorvorrichtung issue a shutdown command and a warning signal indicating that the biosensor device is not functioning in the intended manner.

If the filter monitoring control device further preferably has an evaluation device for evaluating the of the

Filterüberwachungssteuerungseinrichtung has received signals, it is capable of evaluating the received signals and to interpret correctly.

For example, the flow rate through a filter depends on many different parameters. Significant influencing factors include 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, it comes to a higher Flow through the membrane at lower differential pressure. As a result, one additionally obtains an increased filtered total volume at the same time. A

The 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 which fluids such

Cleaning fluids and / or detection fluids such as e.g. Dyes can be tempered locally. Advantageously, the filter has at least one

Heater structure, which particularly preferably comprises a conductor as Heizmäander, and which can be preferably protected by a passivation layer of Si0 ₂ , Al ₂ 0 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. By this storage, an automatic operation of the cleaning device is made possible, as so, depending on the size of the vessel, rarely the fluids must be replenished.

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 example via a valve connected to the cleaning device. Preferably, a valve is provided which can select multiple vessels. This can, depending on the valve position, also different cleaning liquids are 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.

To transport the cleaning liquid, it is advantageous if the

Cleaning device comprises a pump. This pump can do the

Cleaning fluid from the vessel in which it is stored, pump 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 have several pumps in the biosensor device

provided.

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. So the pump can be several

Perform 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 out. Such a construction can save space in the biosensor device. Preferably, the cleaning liquid is also a simultaneously

Reaction fluid used in the detection of biological particles in the

Biosensor device is used. This can also make room in the

Biosensorvorrichtung be saved, as instead of many vessels, some for

Cleaning liquids and some for reaction liquids, only a few vessels for storage of selected liquids 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. Is this sufficient?

However, cleaning the filter is not enough, it is also possible to use a stronger or stronger acid or a strong base to clean the filter.

Organic impurities are preferably by alcohols or

Detergents removed. It is also conceivable to have several purification steps

in which different cleaning liquids are rinsed one after the other 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 depends on the cleaning process of the filter with the

Cleaning fluid is optimized. 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, to avoid overheating and hypothermia

Temperature sensors on the vessels and the filter provided. To determine the exact temperature of the fluid, a temperature sensor is used advantageously introduced directly into the river. 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 conductor tracks

different materials to form a thermocouple, or applying a Leiterbahnmäanders, in the form of a temperature-dependent

Resistance change allows the temperature measurement. The temperature sensors can each be protected by a passivation layer. Advantageous is a recycling facility for reprocessing the

Cleaning liquid provided. 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

Megasound proposed for cleaning filters. 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 filters or in so-called. Track-etched filter membranes. Depending on the design of the

However, filter elements or the megasonic transducer is also a Deep cleaning 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. Of 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 of the sample material. Thus, instead of filtering the water sample (means accumulating the bacteria on the filter surface), adding the probes, reacting the probes with, for example, the bacteria, rinsing unbound probes, detecting, staining also in advance in the separate

Reactor take place. 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 area of detection is advantageous from the rest of the biosensor device disconnected. 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. he can as

Ultrasonic generator, in particular as a megasonic generator, be formed. 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, can

for example PZT (lead zirconate titanate) or AIN (aluminum nitrate) as

piezoelectric layer are applied.

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

The piezoelectric material can preferably by another layer, a passivation layer, against environmental influences, in particular

Cleaning media to be protected.

Furthermore, the geometry of the membrane and the underlying mechanical support structures under the membrane can be adjusted to allow the

Vibration behavior of the membrane at the selected vibration frequency is favorable. Immediately after or even during megasonic cleaning, the

Fluidic system can be activated to perform cross or backwash and thus to improve the cleaning procedure.

Further advantageously, the cleaning device to 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 keeps the meniscus intact.

Advantageously, the EHD unit has a capillary for introducing the

Cleaning fluid from a vessel in the EHD unit, a

Pressurizing 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. Usage rates can typically be in the range of 0.6 to 2

μΙ / minute / nozzle are. This could significantly save costs when using EHD, since high volumes of process chemicals and their rejection after use are avoided.

Advantageously, the EHD unit for forming nanodroplets from the

Cleaning liquid and / or designed to be applied to the filter surface. When starting the EHD current flows through the conductive fluid in 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 the collapse of the meniscus to form an EHD nanodroplet 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. This allows the nanotubes to 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 due to the large number of nuclei in the

Nano droplets worn. This results in energies below material sputtering limits and prevents direct etching or damage to the material

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 perform cross or backflushing 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 transmitted through the electric field

drawn opposite polarized electrode and tear on their way even uncharged particles. Therefore, electrodes for carrying out the are advantageous on the filter

electrochemical cleaning method, in particular as an interdigital electrodes formed. Electrode width and spacing can be z. B. 1 to 10 pm. 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 the backwashing through the filter (by operation of the fluidic system), the particles can be washed away as soon as they pass through the electrophoresis or

Dielectrophoretic process be transported across the filter surface and pass a pore.

Furthermore, the known effect of electroosmosis can be used

(electroosmotic flow in microchannels). Especially at low height of the detection chamber, z. B. 100 to 200 pm, the liquid therein can be pumped when an electric field is applied across electrodes, the across across the filter surface falls off. 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 reciprocating pump corresponds to one

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 backwash and thus the

Cleaning procedure to improve. 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 made of platinum and / or im

Screen printing or formed 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 on. 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 simultaneously, or they one after the other or in a selected combination start. By controlling the pump it is possible, even during one

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 characterized by

Filter monitoring control device activated. If the

Filter monitoring control device 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 the sample material permanently through the

Sampling device can pass.

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 is a part of, for example, drinking water from the

Supply line directed to a bypass. A switchable pressure reducer reduces the pressure and simultaneously the flow rate in this bypass. Is the Fluidikeinrichtung active, so is a constant flow of, for example

Drinking water 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 prohibited

Pressure reducer 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 structure, the sampling device with the

Fluidike device connected to 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. An air bubble sensor for the detection of is advantageous in the Fluidikeinrichtung

Air bubbles provided. 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 of

Fluidike device while it is in a second position on the

Fluidics device passes by. 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. Further, by such a setting, all connections be kept germ-free between, for example, the drinking water line and the filter.

Further 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

Safety device should preferably be designed such that it prevents a backflow of the sample already taken in the line.

This is advantageously achieved in that the safety device a

Check valve is. 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 monitored by the differential pressure measuring device. 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. 1 shows an overview of a biosensor device;

2 shows an overview of a sampling device of the bioses

sorvorrichtung; Fig. 3 shows the function of a switching valve in the sampling device in

Normal operation of the biosensor device;

Fig. 4 shows the function of the switching valve of the sampling device in the De

tektion;

Fig. 5 the retraction of a membrane filter in a conduit in which an interes

flowing sample flows and the subsequent detection of the on the

Membrane filter existing biological particles. Fig. 1 shows a generally designated by the reference numeral 10

Biosensor device for the detection of biological particles. The

Biosensor device 10 has a detection device 12, which has a filter 14 for collecting biological particles for the purpose of detection. In DE 102006026559 A1, DE 102007021387 A1 and not

Prior published patent application DE 102008035772 describes how such, in particular micromechanical filter 14 can be used for the detection of particles, in particular of bacteria. The use of micromechanical filter 14 is hereby made with reference to these three disclosures incorporated in this application. These so-called microfilters consist of a thin, z. B. 1 pm thick membrane, z. B. of monocrystalline silicon or possibly of diamond or 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 mm diameter) are retained on the filter surface, where they can then be detected. These microfilters are in one

Integrated 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 directs a fluid sample via the filter 14. The filter 14 is configured as a filter membrane 18, which can no longer ensure retention of the bacteria on the filter 14 when the filter membrane 18 breaks. Therefore, damage to the filter 14 must be detected under all circumstances. To avoid cracks in the filter 14, or to increase its service life, too high a differential pressure between a first region 20 before the filter 14 and a second region 22 after the filter 14 should be prevented. In addition, pressure fluctuations should not be abrupt, but slow. Therefore, a pump 24, which pumps the sample through the fluidic device 6 to the filter 14, is controlled via a differential pressure measuring device 26. The

Differential pressure measuring device has two pressure sensors 28, 30 in the embodiment shown. The first pressure sensor 28 is designed to measure the pressure in the first region 20 in front of the filter 14, while the second

Pressure sensor 30 is configured to measure the pressure in the second region 22 after the filter 14. The differential pressure measuring device 26 forms a first part of a filter monitoring device 32, which is configured to monitor the filter 14. With regard to the filter membrane 18, two possible errors may occur during operation: The filter membrane 18 is clogged or the filter membrane 18 is damaged. The filter monitoring device 32 has in addition to the

Differential pressure measuring 26 further on a flow amount measuring device 34. This is designed to measure the flow rate through the filter 14, and has a flow sensor 36. The monitoring of the filter 14 can be done by simultaneous measurement of the flow rate and the differential pressure. This can be achieved by a further parameter, for example the flow of the pump 24 or its

Power consumption or its torque to be supplemented. This allows e.g. Recognize blockages or partial clogging of the filter 14 or areas of Fluidikeinrichtung 16. With flow rate kept constant by controlling the pump 24, e.g. the differential pressure with increasing

Increase constipation.

The clogging of the filter membrane 18 depends, for example, in the study of drinking water on the water quality of the examined water and the

Cleaning efficiency. If the water to be examined contains numerous particles, blockage of the filter 14 is more likely.

If there is a blockage of the filter membrane 18, this can be determined 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, which is designed to measure the load acting on the pump 24, indicates that the pump 24 is at full load.

4. One implemented in the filter monitor 32

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 to detect a crack in the filter membrane 18 is to provide sensors on the surface or in the filter membrane 18. In a preferred embodiment, these are conduction paths 44 which cover the active surface of the filter membrane 18. If the filter membrane 18 breaks, the conduction paths 44 are also destroyed and lose their conductivity.

Preferably, to detect a cracked filter membrane 18, an optical detection unit 46 is provided which counts the number of photons emanating from a light source 48. The light source 48 is arranged in front of the first region 20 in front of the filter 14, while the optical detection unit 46 with the second

Region 22 is located after the filter 14. When the light shining through the filter membrane 18 is measured with, for example, a photomultiplier of the optical detection unit 46, an increase in light intensity should never be detected when the filter 14 is intact. Only in the case of a crack of the filter membrane 18 does the light intensity measured by the optical detection unit 46 increase.

Further, the flow rate through the filter 14 depends on many different ones

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 that is built up by the filter membrane 18. This resistance depends inter alia on the porosity of the filter 14. 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 has a voltage measuring device 52, which is designed to measure a mechanical stress on the filter 14. It measures the deflection or the stresses in the filter membrane 18. In the case of micromechanical filters 14, this is possible by integrating piezoelectric elements 54 or strain gauge sensors, which indicate a changed mechanical stress in the event of cracks in the filter membrane 8.

A great influence on the stability of the filter membrane 18 has the material used. This is characterized by the material constants Elasticity modulus, Poisson's number, i. Quercontraktionszahl, and tensile strength, wherein the breaking strength of the filter membrane 18 depends primarily on the thickness of the filter membrane 18. Another influencing factor is the aspect ratio of the filter membrane 18. Optimal stability values are obtained with an aspect ratio of 1 to 1. A microfilter normally always consists of the filter membrane 18 and a back support structure. Since the filter membrane 18 is connected to the support structure, this causes the dimension of the active filter surface and thus the aspect ratio of the membrane. By loosening the filter membrane 18 from the support structure, one has the opportunity to distinguish by a suitable design of the front, i. the filter membrane 18 to make the aspect ratio of the filter membrane 18 independent of the support structure. Thus one can optimize the stability values. At the same time, by adjusting the back, i. the support structure, improved flow characteristics are realized.

The filter monitoring control device 40 is for receiving signals from both the differential pressure measuring device 26, as well as signals of the

Flow amount measuring device 34, the voltage measuring device 52, the

Conductive paths 44, the optical detection unit 46 and the load measuring device 38 is formed. If the evaluation device 42 evaluates a faulty signal in one of the aforementioned components, the

Filter monitoring control device 40 configured to output a Abschaitbefehls for the biosensor device 10.

Except for the detection of only low bacterial concentrations, the

Sensor information of the system, ie pressure, flow rate, load, etc. are used to assess the detection signal in the optical detection unit 46. An alarm signal due to bacterial contamination of the water can be suppressed, for example, if the sensors do not indicate a certain occupancy of the filter 14. The bacteria must eventually lead to contamination. If this is not recognizable, it can be assumed that an error has occurred in the optical detection unit 46 or in the marking method. 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 provide information about the determination of the clogging of the filter 14

Particle load of the medium to be analyzed. This information can be further processed to e.g. 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. Prefiltration to remove large particles is sometimes undesirable, as e.g. Bacteria in

Biofilms adhere to larger particles and retained by the prefiltration and thus could no longer be detected. A way to analyze despite volume larger volumes and still no possible bacteria

to weed out, is two or more filters 14 different

To use pore diameter. In particular, e.g. in the case of drinking water, the sample is pumped through a filter 14 with 1, 5 pm pore size. The medium passing through the filter 14 is filtered through another filter 14 at 450 nm

Pore size pumped. On both filters 14, the detection takes place. The

analysable sample volume is greater than using only a filter 14 with 450 nm pore size, since 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. By moving on a linear stage, it is possible to inexpensively, without the need for a further optical system, to analyze both filters 14.

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

Minimize autofluorescence of particles. Instead of being detected by a photomultiplier or the like for measuring the total intensity, the surface of the filter 14 can also be imaged using an imaging method, for example a CCD camera. 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 4 is in one

Detection chamber 56 which is bounded by a chamber wall 58 to the environment. The detection chamber 56 can be tempered, in particular it can be heated. The temperature can thus be monitored or regulated.

In order to be able to use the filter membrane 18 again in full quality after an analysis, 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 is provided for automatically cleaning the filter 14. The cleaning device 60 has a plurality of vessels 62 for storing fluids. Among other things, the cleaning liquids stored in the vessels 62, which are needed to clean the filter 14. The cleaning device 60 is connected via a valve 64 to the vessels 62. The valve 64 is configured such that it

select different vessels 62 separated from each other and with the

Cleaning device 60 can connect. The pump 24 pumps the selected fluid from the vessel 62 to the filter 14. It is configured such that it can not only pump the fluid to the filter 14, but also the selected fluid, such as the cleaning liquid, via the filter 14 back / and cross-wash. The cleaning fluid flows through a flow system 66, which is a

Four-way double selection valve 68 is controlled. This directs the pumped fluid from the pump 24 either via one of the pressure sensors 28, 30 on the filter 14, or in a waste 70th To keep the supply of cleaning liquid as low as possible, it makes sense to recycle the cleaning liquid in a recycling device 71. That is, cleaning fluid that flows back to the four-way dual selection valve 68 after cleaning the filter 14 is collected in an extra container, here the waste 70. In this is a particle sieve 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. For this purpose, in the cleaning device 60 a

Tempering device 72 is provided for controlling the temperature of the cleaning liquid. To avoid overheating and hypothermia, the tempering device 72 therefore has a first temperature sensor 74 on the vessels 62 and a second temperature sensor 76 on the filter 14.

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

In addition, the filter 14 is formed as a sound generator 82. It is formed of a piezoelectric material and has electrodes which as

Interdigital electrodes are designed to stimulate the piezoelectric

Materials on. A passivation layer 88 protects the piezoelectric material from external influences that could destroy it.

For even better cleaning, the cleaning device 60 has an EHD unit 90, which performs an electrohydrodynamic atomization of the cleaning liquid and thus cleans the filter 14. The EHD unit 90 has a capillary 92 which directs the cleaning fluid from one of the vessels 62 into the EHD unit 90. By applying pressure to the cleaning liquid, it is introduced into the capillary 92 and passed through it and into a

electrostatic field 94 at the end of Kappillare 92 introduced by a electrical contact 96 is generated. From the cleaning liquid to form nanotubes, which are acted upon on the filter 14, and thus clean the filter 14. In order to achieve an even better cleaning effect of the cleaning device 60, electrochemical cleaning devices for the electrochemical cleaning of the filter 14 are provided. The electrochemical cleaning device 100 is for

Carrying out an electrophoresis or an electro-osmosis or electrolysis. It has electrodes 102, which are formed in a special embodiment on the filter 14 as interdigital electrodes. The interdigital electrodes are made of platinum, as this is particularly resistant to external

Influences is.

In order to control the various cleaning possibilities of the cleaning device 60, a cleaning control device 104 is provided which can activate and deactivate the individual cleaning processes. You can z. B. simultaneously activate the ultrasonic unit and the pump 14 while the EHD unit 90 and the electrochemical cleaning device 100 are deactivated. Other combinations of cleaning are possible.

The cleaning control device 104 is over the

Filter monitoring control device 40 is activated. If the

Filter monitoring control device 40 has detected that the filter 14 requires cleaning, z. B. because it is blocked, it gives a signal to the

Cleaning control device 104, which then the corresponding

Cleaning processes starts. During 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 is provided which detects the occurrence of bubbles and outputs a message to allow these bubbles to be removed.

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

FIG. 2 is an overview showing the sampling device 108. FIG. It has a bypass 1 12, which makes the discharge of the sample, here the drinking water, directly from the line 1 14 possible. The

Sampling device has a discharge / Durchleitvorrichtung 1 16, which permanently discharges sample material from the line 1 14 in the biosensor device 10. At the same time, she permanently leads sample material through the

Sampling device 108 in the detection chamber 56 and through a

Multi-way valve 1 18. Of these multi-way valve 1 18, the discharged water can either be returned to the line 1 14 or the waste 70 are supplied. The bypass 1 12 has the pressure reducer 1 10, which is switchable, and which can be switched so that it either the flow of the

Sample material held constant by the sampling device 108, or prohibited the flow. This is especially the case when a measurement is performed in the detection chamber 56. A flow of the sample material through the

Detection chamber 56 would have only disturbing effect, which is why the flow must be prohibited during this time. In the detection, it is advantageous that the detection chamber 56 has a separate reactor 120 in which the sample material is pre-dyed. This simplifies the reaction of the probes with the bacteria and allows for faster detection on the filter membrane 18. The sampling device 108 is connected to the detection chamber 56 via the fluidic device 16. About the Fluidikeinrichtung 16, the reaction liquids from the vessels 62 by means of the valve 64 in the

Detection chamber 56 are introduced. An additional pump 122 is provided for pumping the sample material from the detection chamber 56 into the waste 70. After a measurement, a certain flushing volume must be passed through the multi-way valve 1 18 in the waste 70 to prevent contamination of the drinking water with process fluids.

FIGS. 3 and 4 show a preferred embodiment in which the supply line to the biosensor device 10 can be cleaned. According to the Drinking Water Ordinance or according to DIN EN ISO 19458 it is provided that the water sample should be as directly as possible Analyzer element, ie to get to the filter 14 to contamination by germs, not in the actual sample but in for example the

Hoses are present to avoid. All sampling containers must be germ-free. A first way to prevent contamination is shown in Figs. 3 and 4. A switching valve 124 is the normal operation of

Biosensor device 10, which is shown in Fig. 3, connected in such a way that the sample material is guided past the Fluidikeinrichtung 16 and thus on the detection chamber 56. At the same time, the biosensor device 10 and in particular the fluidic device 16 can be kept germ-free by means of suitable disinfectants. In a sampling, which is shown in Fig. 4, the switching valve 124 is switched such that the sample material of the Fluidikeinrichtung 16 and thus the detection chamber 56 is fed. The sample material flows through previously disinfected fluidic elements before it reaches the filter. How the filter 14 can be introduced directly into a conduit 126 through which the sample flows is shown in FIG. 5 in four steps. In this case, the

Sampling device 108 a rotator 128 on. This has four different positions, which can be introduced by turning the rotator 128 in the line 126. In the first step 130, a

Recording position for the filter 14 screwed into the conduit 126. Thus, the filter 14 is located directly in the drinking water stream and can trap biological particles. With the further steps 132 to 136, the filter 14 is rotated to various positions at which various processes may take place, for example the visualization of the bacteria in step 132, the detection step in step 134 and the washing step in step 136.

The rotator 128 is configured such that for each of these steps 130 to 136 has a passage 138 which is screwed into the conduit 126 at the position of the rotator 128. So is a permanent, undisturbed

Continued flow of drinking water guaranteed.

In order to avoid contaminating drinking water in the line 1 14 by, for example, reaction liquids or the like in the event of a malfunction of the biosensor device 10, a safety device in the form of a check valve is provided. Thus, no already derived water can flow back into the line 1 14 and contaminate the drinking water.

The biosensor device 10 and its components are thermally insulated and include temperature sensors 74, 76 for controlling the temperature of the cleaning and reaction liquids. All fluids and the entire 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 1 10 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 the measurement of the pressure difference across the filter 14, in particular via two pressure sensors 28, which are integrated in the detection chamber 56. As a result, measurement errors are avoided by a pressure drop between the filter surface and the measuring point outside the detection chamber 56.

Further, the system is monitored via the flow sensor 36, which is connected after the pump 24.

Throughout the biosensor device 10, in the housing, in the detection chamber 56, in the fluidic system 16, temperature sensors are present which provide optimum

Allow temperature control of reagents, media, and components, avoiding overheating and low temperature.

Further, an air bubble sensor 106 is provided which can detect and report bubbles in the fluidics device 16. LIST OF REFERENCE NUMBERS

10 biosensor device

12 detection device

14 filters

16 fluidic device

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 device

44 line 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-selection valve

70 waste

71 recycling facility

72 tempering device

74 first temperature sensor 76 second temperature sensor

78 Ultrasonic unit

80 megasound unit

82 sound generator

88 passivation layer

90 EHD unit

92 capillaries

94 electrostatic field

96 electrical contact

100 electrochemical cleaning device

104 cleaning control device

106 air bubble sensor

108 sampling device

1 10 pressure reducer

1 12 bypass

1 14 line

1 16 discharge / discharge device

1 18 multiway valve

120 reactor

122 pump

124 switching valve

126 line

128 rotating device

130 Step 1

132 step 2

134 step 3

136 step 4

138 passage

Claims

claims

1. A 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) has a filter (14) for collecting biological particles for detection,

characterized by a filter monitor (32) for automatically monitoring the function of the filter (4).

2. Biosensing device (10) according to claim 1,

characterized in that the filter monitoring device (32) comprises 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) and / or a voltage measuring device. Device (52) for measuring a mechanical stress on the filter (14), wherein preferably the voltage measuring device (52) has a piezoelectric E- element (54) and / or preferably wherein the filter monitoring device (32) has a conduction path (44) for the production 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) is formed and / or associated with at least one pump (24) for transporting fluids and / or connected to the pump (24) is t and / or a load-measuring device (38) for measuring the load acting on the pump (24).

3. biosensor device (10) according to claim 2,

characterized in that the filter monitoring device (32) comprises a filter monitoring control device (40) for receiving and / or processing signals and / or outputting a shutdown command for the Biosensorvorrich- 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 amount measuring device (34) and / or the voltage measuring device (52) and / or the line path (44) and / or the optical detection unit (46) and / or the load measuring device (38) is and / or at least one Evaluation device (42) for evaluating the signals received by the Filterüberwachungssteue-- (40) received

4. biosensor device (10) according to any one of the preceding claims, characterized in that a cleaning device (60) for automatically cleaning the filter (14) is provided.

5. biosensor device (0) 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.

6. biosensor device (10) according to claim 5,

characterized in that the cleaning device (60) has 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 the cleaning liquid over the filter (14) and / or the pump (24) of the filter monitoring device (32) is designed as a pump (24) for pumping the cleaning liquid

7. biosensor device (10) according to any one of claims 5 or 6,

characterized in that the cleaning liquid is 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 temperature control of the cleaning fluid and / or to avoid overheating and hypothermia temperature sensors (74, 76) on the vessels (62) and the filter (14) are provided.

8. Biosensing 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) comprises a particle screen and / or activated carbon.

9. biosensor device (10) according to one of claims 4 to 8, characterized in that the cleaning device (60) comprises an ultrasound unit (78), in particular a megasonic unit (80), with a sound generator (82) for acting on the filter (14) Sound waves and / or that the detection device (12) has a filter and / or a separate reactor (120) for pre-inking the sample material and / or a limiting chamber wall (58) having detection chamber (56) and / or that the sound generator (82) is attached to the detection chamber (56) of the detection device (12) and / or that a nozzle for exiting megasonic-loaded fluid is disposed through the chamber wall (58) into the detection chamber (56) on the detection chamber (56) and / or the filter (14) is formed as a sound generator (82) and / or of a piezoelectric material or has a layer of piezoelectric material, in particular of PZT or AIN and / or electrodes, in particular interdigital electrodes, for exciting the piezoelectric material and / or a passivation layer (88) for protecting the piezoelectric material.

10. Biosensing device (10) according to one of claims 4 to 9,

characterized in that the cleaning device (60) has an EHD unit (90) for electrohydrodynamic atomization of the cleaning fluid and / or that the EHD unit (90) has a capillary (92) for introducing the cleaning fluid from a vessel (62) in 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 designed to form nanotubes from the cleaning fluid and / or to act on the filter surface, and / or that the capillary (92) of the EHD unit (90) in the chamber wall (58 ) of the detection chamber (56) is arranged.

1 is a biosensor device (10) according to one of claims 4 to 10,

characterized in that the cleaning device (60) is an electrochemical cleaning device (100) for the 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 cleaning methods are formed on the filter (14), in particular as interdigital electrodes and / or of platinum and / or by screen printing or by vapor deposition or sputtering.

12. Biosensor device (10) according to any one of claims 9, 10 or 1, characterized in that the cleaning device (60) at least one cleaning control device (104) and / or that the Reinigungssteue- tion 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) is formed and / or that the cleaning control device (104) is activated by the filter monitoring control device (40).

13. Biosensing device (10) according to one of claims 9 to 12,

characterized in that a sampling device (108) is provided for picking up, in particular fluid, sample material directly from a line (1 14) and / or that the sampling device (108) has a diverting / passing device (1 16) for permanently discharging the Sample material from the line (1 14) and for continuously passing the sample material through the sampling device (108) and / or that the sample material flows via a to the line (114) connected to the bypass (1 12) in the sampling device (108) Detection chamber (56) flows through tangentially and via a multi-way valve (1 18) back into the line (1 14) is initiated and / or that the bypass (112) has a switchable pressure reducer (110), the flow of the sample material through the sampling device ( 108) and the detection chamber (56) keeps constant and prohibits the flow during a measurement.

14. Biosensing device (10) according to claim 13,

characterized in that the sampling device (108) is connected to the fluidic device (16) for establishing a connection between the sampling device (108) and detection chamber (56) and / or has a switching valve (124) which receives the sample material in a first Position of the Fluidikeinrich- device (16) zuleitet and in a second position, the sample material on the Fluidi device (16) passes by and / or a rotating device (128), wherein the rotating device (128) is formed with at least one passage (138) and at least one receiving position for at least one filter (14) and / or that the rotating device (128) can be screwed into the line (126) in at least two positions, the at least one filter (14) is positioned in the conduit (126) in a first position and in a second position the at least one passage (138) is positioned in the conduit (126).

15. Biosensing device (10) according to claim 14,

characterized in that at least one air bubble sensor (106) in the Fluidi device (16) for detecting air bubbles and for outputting a message and / or a safety device (140) is provided, which prevents contamination of the line (1 14) in case of failure and / or that a check valve (142) is provided which forms the safety device (140) and / or that the at least one differential pressure measuring device (26) is designed to control the pump (24).