AMPLIFYING DEVICE OF CONCENTRATION Of PRESENT ANALYTES IN an ATMOSPHERE AND SYSTEM OF DETECTION ASSOCIATES

The present invention relates to sensors for detecting analytes present in an atmosphere, such as particular chemical or biological species.

In many industries (agri-food, pharmacy...), in the field of safety and industrial prevention, civil (home pollution) and in the military, sensors are used to enable detection of an abnormal concentration of certain analytes in the atmosphere, to prevent the hazardous effects, for example the explosion, poisoning, or contamination. For this purpose, chemical sensors or biosensors are used. In the biological field, it is necessary to detect toxins that are hazardous, some bacterial toxins such as bacillus anthracis or the botulinum toxins, or certain viruses, such as smallpox, influenza... In the field chemical, is known the hazards of organophosphorus derivatives (sarin, tabun...) and TNT.

A chemical sensor is a system that uses chemical reactions for detecting an analyte. It creates a link between the chemical recognition element, which reacts with the analyte, to a transducer which connects the chemical recognition to a useful physical signal, and converts the physical signal into an electrical signal.

It is typically made:

an interface chemical sensitive, which interacts with the analyte to be detected. The interaction between the analyte and the chemical sensitive interface by physico-chemical sorption causes a change in a measurable physical parameter of the interface, for example, the mass, the electrical conductivity, the temperature or the optical reflectivity.

-a transducer, which converts the same particular chemical interface, into an electrical signal, e. g., a voltage, a current, or a frequency or an optical signal. This signal is then processed by any appropriate instrumentation.

Similarly, a biosensor is a system that uses biological reactions for detecting an analyte. It creates a link between the biological recognition element, which reacts with the analyte, to a transducer which connects the biorecognition useful in a physical signal, and converts the physical signal into an electrical signal.

More specifically, and as schematically represented in Figure 1, a biosensor Bcapt is based on the selective grafting of a target analyte has_c (the analyte to be detected) on a receptor ligand L_r . The ligands receptors are immobilized on the sensor surface Scapt , forming a layer of molecules selected for their recognition properties of said analyte. In systems called affinity, the transducer TD is directly responsive to the attachment (graft) of the target analyte on the ligand. In the catalytic systems, or metabolic, an enzyme is used as a reactant. The enzyme catalyzes a biochemical reaction at which the transducer is responsive. The transducer TD outputs an electric signal S_e in response to the signal detected physical.

The sensors are generally ranked transduction principles used.

The optical sensors use a light source to directly excite the target analyte or an analyte (e.g. polymeric) which undergoes a change in the presence of the target analyte, and means for examining variations in the optical properties resulting: absorption, reflection, fluorescence. Chemical sensors using the type of transduction are particularly useful for the detection of chemical vapors that contaminate the environment of an anti-personnel mine (detection of TNT). A known device comprises an excitation light source, typically a laser diode, two transparent substrates coated with a layer of fluorescent polymer, which form a planar waveguide for the light emitted by the polymer. The air flow passage comprising trinitrotoluene (target analyte) in the waveguide alters the fluorescent properties of the polymer (quenching). A interference filter passes the light emitted by the polymer and blocks a large part of the light emitted by the source. A photomultiplier type (tube or photodiode) measures the intensity of the fluorescence. Optical biosensors comprise The for their part optical transducers using e.g., fluorescence or radioactivity.

Sensors resistance change that rely on the change of the conductance of a conductive polymer film or a semiconductor film mineral induced by the sorption of gas and by the chemical reactions derived therefrom. A known structure such as a porous thin film semiconductor (metal oxide such as WO3 or Sn02, ZnO... doped with platinum or palladium) deposited on a heated ceramic. The Heating enables to improve the kinetics surface reactions.

Sensors mass variation, typically the acoustic wave sensors, the sensors or piezoelectric vibration. For example, a surface acoustic wave sensor comprises an interdigitated comb transmitter, a receiver, and a sensitive membrane formed of a metal oxide or a polymer, arranged between the transmitter and the receiver. The adsorption/absorption of analyte molecules by the sensitive membrane, causes a change in the mass and the viscous-elastic properties of said membrane, which causes a disturbing the transmission of the surface wave. The membrane material is selected based on the analyte to be detected.

Other types of sensors exist that will not be detailed. The different sensors of the prior art generally have the disadvantage of being non-selective: they react to more than one analyte, thereby impeding their identification and classification.

A further drawback of these sensors is their low sensitivity:

their detection threshold is generally greater than the threshold of toxicity or severity of some analytes, active, low concentration. For example, toxic chemical agents such as nerve agents types G (sarin, tabun), the blistering agents such the yperite, the yperite-nitrogenated and the lewisite , have in common be of highly toxic agents, and active at low concentrations, typically 0.01 mg/kg. The sensors of the prior art are not able to achieve such sensitivity thresholds.

There is a certain interest to be able to detect their presence at low detection threshold, below a threshold said toxicity or contamination.

The analyte sensors of the prior art are not all operative for such detections to low threshold.

An object of the invention is to provide a technical solution to this problem of detecting analytes in low concentration.

The basic idea of the invention is to support the analyte concentration in the environment of the chemical sensor.

In the invention, following the observation is that a number of toxic or hazardous analytes are characterized by molecules of size of order one nanometer to a few nanometers.

Among these analytes include organophosphorus derivatives (sarin, tabun, ...) but also the TNT, that are molecules of near-nanometer size. The analyte molecules virus like, have sizes of between 20 and 300 nanometers. Bacterial toxins The molecules have sizes of between 1.71 nanometres and 271.

In the invention, a technical solution to the problem has been found in the use of two nanoporous membranes, the diameter of the nanopores of the first membrane being greater than the diameter of the nanopores of the second membrane, and of a device capable of forming a flow of air in the direction from the first to the second membrane, to enclose in the space between the two membranes, analytes, the size of which is between the two diameters.

By placing a sensor or the sensitive surface of the sensor within the space, the response of the sensor matches with the amplification factor obtained. The detection threshold equivalent of a system comprising an amplifier concentration in the invention in combination with a chemical sensor is significantly lowered, for the detection of analytes of interest at low concentrations.

As claimed, the invention provides a device for amplifying concentration of analytes present in an atmosphere, comprising a first and a second nanoporous membrane nanoporous membrane disposed within a duct, and forming a cavity within the conduit, the diameter of the nanopores of the first membrane being greater than the size of the analytes to be detected, the diameter of the nanopores of the second membrane is less than the size of said analytes, and a pump device being provided for causing an input flow current by the first membrane and exiting the second.

The device in concentrates in the the target analytes, having a size between the two diameters of the membranes. The other analytes in the observed atmosphere, is do not penetrate in the, because the molecules are too large relative to the inlet diameter (diameter nanopores of the first membrane) are either rejected via the second membrane, in their molecules are smaller than the outlet diameter (diameter nanopores the second membrane). Typically these are the main constituents of the atmosphere (oxygen, carbon oxide, di-nitrogen oxide... andc).

By adapting the diameter of the nanopore membranes, depending on the size of the analyte species to be searched, the selectivity of the sensor is improved. Now known separating molecules with accuracy of the order of nanometers.

In an improved embodiment, to reduce the risk for attachment of the molecules to the walls of the nanopores of the entry membrane, is provided line the walls of the nanopores by a material taken as nanotubules. In this way the transport of analytes through the nanopores of large diameter is optimized.

Furthermore, to further reduce likely to be caught, is provided one embodiment of the membranes according to technology "film supported" (medium layer), to provide a membrane thickness particularly optimized, low.

The invention also relates to a detection cell of one or a plurality of analytes, comprising a device for amplifying concentration associated with a sensor or a chemical sensor array and an air circulation device.

The sensor may be of any technology, in particular of a resistance, or optical mass variation.

According to one aspect of the invention, for application to the detection of analytes such as type biological toxins or viruses, the sensor is a biosensor.

Other advantages and features of the invention will appear more clearly from a reading of the description that follows, made as indicative and non-limiting of the invention and with reference to the accompanying drawings, in which:

already described-Figure 1 is a block diagram of a biosensor, according to the state of the art;

-figures 2a to 2c show a nanopore membrane used in the invention, in a top view, and, according to the technology used, or carrier film;

-figure 2d shows the constitution of a nanopore to nanotubule used in one embodiment of the invention;

-figure 3 is a block diagram of a simplified amplifier device according to the invention;

figure 4-is the principle of concentration of the invention, by the diameter of the pores of the membranes of the amplifier device according to the invention;

figure 5-is a block diagram of one embodiment of a system for detecting gaseous species comprising an amplification device according to the invention;

-figure 6 represents an alternative embodiment of such a system;

-figure 7 represents schematically a integrated ventilation system; and

figure 8-is a schematic illustrating one example of an embodiment of the assembly of two membranes obtained according to technology supported film.

The amplification principle according to the invention is applicable to nano-sized molecules, to permit their detection well before the limit threshold toxicity. It is generally applicable to molecules of size close to or higher than the nanometer. Listed previously are a number of chemical species entering the windows size of molecules: chemical species such sarin, tabun, or the TNT (between 0.7 and 0.8 nm), viruses (between 10 and 300 nm), toxins, in particular bacterial toxins (between 1.71 and 271 nm).

A sensor according to the invention is particularly suitable for detecting low threshold of these analytes, in order to prevent any toxicity or allow placement of provisions to prevent risk of contamination. It is in particular of use in the detection of chemical weapons or bacteriological, but also for preventing any risk of contamination (hospitals, airports for example).

On Figure 3, is schematically represented a amp amplifier device according to the invention. It comprises a conduit 1 of any shape, for example a tube of round cross-section as shown. Both could have a rectangular tube. The conduit 1 may be in any suitable material, such as glass, quartz, plastic or metal.

The conduit comprises two membranes m1 and nanoporous m2. It has a cavity 2 which the space is defined by the two membranes and the conduit. The assembly can for example be obtained using a suitable method of bonding or assembly of membranes.

A nano-porous membrane is a material well known, generally obtained from a polymer membrane. In one possible method of manufacturing, in a first step, the membrane is exposed to a flow of high-energy ions which passes right through it, and which damages its structure. In a second step, combination treatment chemistry provides optical and reveal the straight path of the ions and thereby form nanopores substantially cylindrical shape.

The density of the pores is statistically controlled by controlling the flow of ions.

Nanopores The diameter is controlled by the parameters developing. With the current technologies, accuracies is reached for separating molecules by their size with accuracy of the order of nanometers.

Fabrication techniques nanoporous membranes are well known and numerous publications. They will not be detailed further.

A nano-porous membrane is shown in Figure 2a, in plan view. It comprises a plurality of nanopores, controlled density. The density will typically depend on the diameter of the nanopore. Current technologies allow The a pore density of the order of 10⁴ TO 5.10⁹ nanopores by cm² .

Two manufacturing technologies are mainly used. The technology said film (thick film technology) and technology supported film (thin film technology).

A membrane obtained according to the film technology is represented in cross-section on Figure 2b. The membrane is a polymer film Pou (polycarbonate, PET, polyimide...) thickness ℮ 1 typically between 10 and 25 microns.

A membrane obtained according to the technology supported layer is represented in cross-section on Figure 2c. The membrane is a polymer film P₀ i2 (polycarbonate, PET, polyimide...) deposited everywhere method suitable thin film, thickness ℮ 2 typically between 0.2 and 5 microns, on a substrate S, for example a silicon substrate.

In a first example assembly of membranes to form an amplifier device according to the invention as shown in Figure 3, the membranes are formed as thick film. They are each assembled by any appropriate means (mechanical connection, bonding) to the conduit.

In another exemplary assembly schematically represented in Figure 8, each of the membranes is achieved as a thin film deposited on a substrate. Is provided then etching of the substrate S1, S2 of each membrane m1, m2, and assembling the two membranes by their substrates so that the etched portion of the substrate of each membrane forms the amplification cavity of the sensor according to the invention. The conduit of Figure 3 is thus made by the substrates S1 and S2 membranes.

Amp amplification The device further includes a device (Figure 2) 3 air circulation, typically a pump or a fan, adapted to create an incoming air stream (Fe) by the first membrane and an output flow (Fs) by the second membrane. The device 3 air circulation is typically provided at the bottom of the conduit.

In the invention, and as more particularly detailed in Figure 3, the first membrane is selected that receives the incoming stream Fe, with nanopores d1 diameter and the second diaphragm which allows for the flow exiting Fs, with nanopores d2 diameter, with d1 > d2.

Therefore, analyte molecules contained in the incoming stream which have a size less than d1; m1 will pass through the membrane. Among the molecules that permeate the membrane m1, analyte molecules which have a size d_M between d1 and d2 are captive in the cavity 2, while those which have a size of d_m less than d2 project out of the cavity by the membrane m2, in the output stream.

According to one embodiment of the invention, d1 is selected greater than the size of the molecule of the target analyte that is to be detected, for example in a ratio two, to reduce the risk of hanging of the analytes to the inner walls of the nanopore.

In order to reduce the risk of catching and to improve the sensitivity of the device according to the invention, is provided preferably line the walls of the nanopore with a material that optimizes the transport of analytes within the nanopores. This may be as nanotubules of the material, arranged in the nanopores using technological methods for the synthesis of nano-objects in the pores well known. On Figure 2d, is cross section such a nanopore whose inner walls are lined with material nanotubule.

The diameters d1 and d2 nanopores the membrane m1 input and output of the membrane m2 and the thickness nanotubules (which reduces the useful internal diameter nanopores) are determined according to the size of desired analyte, with all the precision allowed by the technology.

Or, reduce the risk of catching, preferably thin film membranes. The membranes are typically obtained by a production of said membranes "film supported" (medium layer), to provide a membrane thickness particularly optimized, low (thin film technology), typically less than 5 microns.

According to another aspect of the invention, is provided determination of densities of nanopores pi membranes, ρ2 and their diameters di and d2 so as to create pressure conditions favorable to the detection, i. e., to that the cavity be prevented from remaining or overpressure or depression. This can be achieved with a surface of nanopores equivalent between the two membranes, which is written as follows:

-the surface S "represented by the nanopores of the first membrane is given by: S"=

st2-the surface represented by the nanopores of the second membrane is given by: St2 = ρ2^/4.π^2²

Thus is selected (p1, d1) and (p2, d2) for that: S_t i=St2.

In this way, the pump does not cause any pressure variation within the cavity 2.

In a practical embodiment a concentrator according to the invention, as shown in Figure 4, the amplifier device comprises a concentration of amp inlet neck 4, funnel-shaped, which can improve the performance of collection of analytes within the cavity 2. If takes place in the context of a conduit with a circular cross-section, and if it is note D1 the outer diameter of the neck and D₂ , the inner diameter of the neck, is obtained additional an amplification factor equal to the square of the ratio of the diameters. Either, assuming Di=10cm D2=1cm and for example, an amplification factor additional 100.

D The diameter₂ , or more generally the width of the duct section 1 typically corresponds to the dimension of the passage 1.

According to the invention, a system for detecting analytes in vapour or gas phase, present in an atmosphere, amp amplifier integrates a device according to the invention, a sensor 10 for detecting analytes and a pump device 3. The amplifier and the pump device are typically integrated into the conduit 1, as shown in Figure 4, with the air circulation device (a fan or a pump) arranged at the bottom of the conduit, and the sensor 10 may be disposed within the cavity in the conduit, or outside the cavity, on the conduit.

The sensor can be a chemical sensor or a biosensor, transducer of any type, in particular, it may be of the optical type, variable mass or resistance. It is suitably arranged to perform detection of analytes of interest in the enclosed atmosphere of said cavity (2). In practice, it can be disposed outside or inside of said cavity (of the conduit) based on the technology considered.

In the case of a biosensor, at least the receiving surface of the sensor Scapt (Figurel) is located within the cavity.

In the case of a sensor optical transducer, is preferably provided that the optical system is orthogonally disposed with respect to the flow direction Fe = > Fs, rather than collinear, in which case prior transparent membranes. The conduit would be in one such application type glass or quartz, or more generally in any material transparent to the operating wavelength of the sensor. Been that in this case, the sensor 10 or at least the part of the sensor optical transduction, is arranged outside the amplifying device amp, on the conduit, at the cavity, by any suitable mounting. Such mounting is shown schematically in Figure 4.

If the technology the sensor used provided the reaction with an analyte detection, is provided an injection system said analyte within the cavity.

In the case of other technologies chemical sensor or biosensor, the sensor 10 is typically disposed within the cavity 2, as shown schematically in Figures 5 and 8. In other words, the sensor is integrated in the amplifier amp device. In practice, the sensitive part 13 comprising the interface and the transducer would be in the cavity, while the portion 12 measurement instrumentation and supply would be outside.

In practice, there is further provided a reversal system and flow diversion to enable periodically purging the cavity 2. One example of an embodiment of such a system is detailed in connection with fig. 6.

Typically, such a system is carried out by means of solenoid valves, arranged and controlled to into detection phase, the air circulation device 3 imposes the flow Fe = > Fs, and in purge phase, the direction of flow in the cavity is inverted, with an air inlet provided in the duct between the second membrane and the air circulation device, so as to form a flow of incoming purging Fp by the second membrane and a purge stream exiting Fsp by the first by means of a conduit 5 (by-pass) bypass. In the example, the purge stream exiting Sanitized is into the atmosphere via the 3 air circulation.

In the example, is provided a first valve assembly and v1 v2, for the detection phase, and a second set of valves v3, v4 and v5 for the purging step.

Valves and detection The v1 v2 are positioned in the conduit 1 on either side of the cavity 2 and each prior to entry, respectively exit from the bypass duct 5. They are controlled on into detection phase and to said closed state in purging phase.

The drain valves v3, v4 and v5 are not arranged in the conduit 1. V3 The valve controlling the opening of the air inlet purge is provided for isolating the inlet of the conduit 1, at the output of second membrane. V4 v5 The valves and respectively are arranged to isolate the inlet and exit from the bypass duct 5, of the conduit 1. These valves are controlled in the closed state into detection phase and on in purging phase.

Therefore, the first and second sets of purge are controlled in a complementary manner, according to the operational phase of the system: detection or purging. In practice the air circulation system will be dimensioned relative to the volume of the cavity and stress gating period of the purging. Since order of magnitude, there may be an air flow rate of 1 cm³ / s.

Can be to provide a system to two pumps, one for the detection and the other for purging.

The invention is not limited to the exemplary embodiments described. In particular all embodiments required by the integration of a particular sensor are within the scope of the invention.