Classifications

• • G—PHYSICS
  • G03—PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
  • G03F—PHOTOMECHANICAL PRODUCTION OF TEXTURED OR PATTERNED SURFACES, e.g. FOR PRINTING, FOR PROCESSING OF SEMICONDUCTOR DEVICES; MATERIALS THEREFOR; ORIGINALS THEREFOR; APPARATUS SPECIALLY ADAPTED THEREFOR
  • G03F7/00—Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printing surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
  • G03F7/20—Exposure; Apparatus therefor
  • G03F7/24—Curved surfaces
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B81—MICROSTRUCTURAL TECHNOLOGY
  • B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
  • B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
  • B81C1/00015—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems
  • B81C1/00206—Processes for functionalising a surface, e.g. provide the surface with specific mechanical, chemical or biological properties
• • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
  • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
  • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
  • F04B19/00—Machines or pumps having pertinent characteristics not provided for in, or of interest apart from, groups F04B1/00 - F04B17/00
  • F04B19/006—Micropumps
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B81—MICROSTRUCTURAL TECHNOLOGY
  • B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
  • B81B2201/00—Specific applications of microelectromechanical systems
  • B81B2201/02—Sensors
  • B81B2201/0214—Biosensors; Chemical sensors
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B81—MICROSTRUCTURAL TECHNOLOGY
  • B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
  • B81B2201/00—Specific applications of microelectromechanical systems
  • B81B2201/05—Microfluidics
  • B81B2201/058—Microfluidics not provided for in B81B2201/051 - B81B2201/054
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B81—MICROSTRUCTURAL TECHNOLOGY
  • B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
  • B81B2201/00—Specific applications of microelectromechanical systems
  • B81B2201/06—Bio-MEMS
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B81—MICROSTRUCTURAL TECHNOLOGY
  • B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
  • B81C2201/00—Manufacture or treatment of microstructural devices or systems
  • B81C2201/01—Manufacture or treatment of microstructural devices or systems in or on a substrate
  • B81C2201/0101—Shaping material; Structuring the bulk substrate or layers on the substrate; Film patterning
  • B81C2201/0147—Film patterning
  • B81C2201/0154—Film patterning other processes for film patterning not provided for in B81C2201/0149 - B81C2201/015

Definitions

• the present invention relates to a method of functionalization of one or more fluidic veins covered with an opaque wall, for example made of silicon. It also relates to devices containing fluidic veins that can be functionalized, as well as to their method of production.
• fluidic vein is understood to mean any tubular structure comprising a peripheral wall laterally delimiting a space in which a fluid may circulate, and comprising an inlet and an outlet.
• the cross section of a fluidic vein may be arbitrary (circular, polygonal, etc.) constant or not along the vein.
• a capillary, a conduit, a pipe are synonymous with the notion of fluidic vein used in the invention.
• the functionalization of a surface is the operation by which one or more molecule (s) of interest are fixed on a surface, so that it (s) retains (s) all or part of its (their) properties.
• the functionalization of a surface therefore supposes that the molecule of interest and an associated process are available to fix it on the surface.
• Several types of surface functionalization methods are known from the prior art. Traditionally, they consist in modifying the surface to be functionalized by means of chemical reactions aimed at generating functions that can be reactive with respect to a probe molecule. Said probe molecule then being used to capture a target whose presence is ultimately to be detected.
• the main difficulties encountered in these surface functionalizations lie in the choice of reactive chemical functions that can be implemented to obtain the immobilization of the probe on the surface of a support. For example, the chemical nature of the surface of the substrate should be taken into account.
• the silane-type molecules are widely used.
• a molecule having a silane functional group capable of reacting with the silicon support via the surface silanols and a reactive function masked or not with respect to a probe molecule, optionally chemically modified, is then used.
• the probe molecule is positioned on the silane molecule via the use of complementary reactive functions.
• a support in silicon for example, the zones that will have to undergo a functionalization, one uses conventionally techniques of reactions localized by automaton (or "spotting" in English) making it possible to locate precisely the ejection of the silane and consequently, to define successive and isolated zones functionalized by silanes of different natures.
• silanes having a function masked by a photolabile group There are also silanes having a function masked by a photolabile group. After fixing on the surface of a support, said silanes are deprotected to release a function which is itself reactive with respect to a complementary function carried by a probe molecule. By the use of a selective insolation, the photo deprotection can be localized and make it possible to differentiate areas on the surface of the support.
• silane includes the need to make the surface accessible to insolation conditions, which therefore poses a problem when the surface to be selectively functionalized is part of a closed cavity whose walls are opaque, for example silicon or other opaque material.
• a process for functionalizing substrates having, inter alia, the capillary form, has been described in WO 2006/024722. Functionalization of the capillaries was carried out by deprotecting the reactive functions of a compound by insolation with the aid of an ultraviolet lamp, and then bringing the surface of the activated capillaries into contact with a solution of the biological molecules of interest. .
• the capillaries thus activated are necessarily made of glass and are transparent to UV light.
• the object of the present invention is therefore to provide a method of functionalization of the fluidic veins whose walls comprise an opaque layer.
• the subject of the invention is therefore a method for functionalizing a micro mechanical device provided with a fluidic vein comprising a wall device having an outer surface to the vein and an inner surface defining a space in which a fluid is likely to circulate, the peripheral wall comprising at least partially a silicon layer, characterized in that it comprises the following steps:
• the method may comprise a step b) of hydration of at least the internal surface of the fluidic vein.
• the device is a micromechanical device, such as for example a resonator used as a gravimetric sensor.
• the internal surface of the fluidic vein is hydrated.
• the hydration step may include immersing the device in an alcohol and metal hydroxide solution or an alcoholic acid solution.
• the silanization step may comprise immersing the device in a solution containing photosensitive silanes.
• the silane used in the silanization step can be a photosensitive oxyamine silane.
• photosensitive silane is understood to mean a silane-type molecule comprising a silanized group capable of reacting with a silicon-type surface and a photolabile group protecting a reactive function for the purpose of grafting a probe molecule.
• UV light lamp Preferably, this lamp has a power of 100W and an intensity of 20 to 25 mW / cm 2 , preferably of the order of 24 mW / cm 2 ;
• the exposure can be carried out sequentially or simultaneously;
• the duration of insolation is generally between 5 and 30 seconds;
• sequential insolation can be achieved with a ray of UV light which passes through a mechanical opening of adjustable width;
• sequential or simultaneous insolation can be performed on a device covered with a layer of opaque patterns at the irradiation wavelengths of the silane;
• sequential or simultaneous insolation may be performed using a quartz photolithography mask comprising micron units capable of filtering the UV light;
• sequential or simultaneous insolation can be achieved by using a photolithography mask combined with a masking of opaque patterns;
• the method of the present invention may furthermore comprise a step of grafting at least one molecule onto the fixed silanes on at least one surface of a fluidic vein by means of of a pair of chemical functions carried by the molecule to be grafted and the silanes.
• the deprotected silane is capable of reacting with a chemically modified probe molecule or not to immobilize said probe molecule on the internal surface of the fluidic vein.
• the molecules to be grafted may be macromolecules, chosen from nucleic acids, lipids and / or proteins;
• the molecules to be grafted may be oligonucleotide probes.
• the method of the present invention may further comprise a hybridization step, followed by a fluorescence read step.
• the method of the present invention may further comprise a hybridization step, followed by a step of detection and / or characterization of the hybridization. In particular, this detection step can be done by means of electrical means.
• the present invention also aims to provide a micromechanical device containing fluidic veins whose wall comprises at least partially an opaque material layer and which can be functionalized by the method of the invention.
• Another object of the present invention is therefore the provision of a micromechanical device capable of being functionalized by the method of the invention, the device being provided with a fluidic vein comprising a peripheral wall having an external surface to the vein and an inner surface delimiting a space in which a fluid is likely to circulate, the peripheral wall comprising at least partially a silicon layer, the device having, at least locally, a thickness of between 100 and 200 nm excluded, preferably between 160 and 180 nm, and the inner surface being silanized.
• the silanized internal surface may be at least locally deprotected where the thickness of the wall is between 100 and 200 nm excluded, preferably between 160 and 180 nm;
• the silanized internal surface deprotected locally may comprise grafted molecules
• the grafted molecules can be probes.
• Probe means molecules capable of detecting specific targets.
• the device of the present invention may be a device for the gravimetric detection of particles in a fluid medium, comprising a planar electromechanical oscillator, oscillator support means and means for actuating said oscillator, said means being arranged to vibrate the oscillator, said device further comprising a channel for the passage of the fluid, the electromechanical oscillator comprising a throughflow fluidic fluid in upstream and downstream fluid communication with said channel, the vein having a surface internal device delimiting a space in which a fluid may circulate, and being delimited at least partially by a peripheral wall comprising a silicon layer having, at least locally, a thickness of between 100 and 200 nm excluded, preferably between 160 and 180; nm, the inner surface being silanized.
• the silanized internal surface may be at least locally deprotected where the thickness of the wall is between 100 and 200 nm excluded, preferably between 160 and 180 nm; the silanized internal surface deprotected locally may comprise grafted molecules by contacting said molecules with the photodeprotected function of the silane;
• the grafted molecules may be probes
• the electromechanical oscillator may have a shape taken from a disk, a ring and a polygon, preferably a square;
• the oscillator may be square in shape and have a width and a thickness such that the ratio of the width to the thickness is between 10 and 30, preferably 10;
• the electromechanical oscillator can be obtained from a substrate layer of polycrystalline material
• the electromechanical oscillator can be obtained preferentially from a substrate of monocrystalline material
• the substrate may be based on silicon
• the electromechanical oscillator may comprise or be obtained from metals deposited by PVD (vapor phase deposition) method, evaporation or electrolytic growth;
• the oscillating fluidic vein of the oscillator and / or the channel contains pillars of cross-sectional shape taken from a circle, an ellipse, and a polygon.
• the peripheral wall comprising the silicon layer may comprise a metal material for detection by transduction (piezometallic, capacitive, thermoelastic), optionally in the form of a track.
• said metallic material may have a mask function for photodeprotection and a detection function within the scope of the invention.
• the present invention also relates to a method for producing a device according to the invention, comprising the following steps:
• a substrate suitable for the gravimetric detection envisaged comprising, at least partially, a layer of silicon, the production from said substrate of a planar electromechanical oscillator and at least partially comprising the silicon layer,
• the wall comprising at least partially the silicon layer has, at least locally, a thickness of between 100 and 200 nm excluded, preferably between 160 and 180 nm,
• the present invention also relates to the use of a photochemical functionalization method with a device provided with at least one fluidic vein having a wall at least partially opaque to the wavelengths used by the insolation to activate the reaction.
• photochemical wherein the device is provided with a fluidic vein whose peripheral wall comprises at least partially a silicon layer having, at least locally, a thickness of between 100 and 200 nm excluded, preferably between 160 and 180 nm.
• FIG. 1 is a schematic sectional view of a portion of a device comprising a fluid stream capable of being functionalized according to the method of the invention
• Figure 2 a schematic sectional view (Figure 2b) and top view ( Figure 2a) of a device similar to that of Figure 1 during a sequential insolation;
• FIGS. 5, a diagrammatic sectional view (FIG. 5b) and top view (FIG. 5a) of a device similar to that of FIG. 1 during sequential exposure with a photolithography mask combined with the pattern mask. opaque;
• Figure 6 a schematic sectional view (Figure 6b) and top view ( Figure 6a) of a device similar to that of Figure 1 during an insolation simultaneously in full plate with a photolithography mask;
• FIG. 7 is a diagrammatic cross-sectional view (FIG. 7b) and top view (FIG. 7a) of a device similar to that of FIG. 1, in simultaneous insolation in full plate with an opaque pattern mask; ;
• FIG. 8 is a schematic sectional view (FIG. 8b) and top view (FIG. 8a) of a device similar to that of FIG. 1 during the probe attachment step after sequential insolation;
• FIG. 9 is a diagrammatic sectional view (FIG. 9b) and top view (FIG. 9a) of a device similar to that of FIG. 1 during the probe attachment step after sequential insolation with the mask of FIG. opaque patterns;
• FIG. 10 a schematic perspective view of an embodiment of a functionalizable device according to the method of the invention.
• FIG. 11 a schematic perspective view showing the interior of the fluidic vein of the device of FIG. 10
• FIG. 13 a schematic perspective view of a device similar to that of Figures 10 and 11;
• FIG. 14 is a schematic sectional view of an embodiment of a device according to the invention comprising a structured metal layer on the silicon layer of the fluidic vein.
• the functionalization method according to the invention is useful for the functionalization of a micromechanical device such as that shown in FIG.
• This device is provided with at least one fluidic vein 1b comprising a peripheral wall 5 having an external surface 2 to the vein and an inner surface 3 defining a space in which a fluid is likely to circulate.
• the peripheral wall 5 comprises, at least partially, a silicon layer 5a, having, at least locally, a thickness e of between 100 and 200 nm excluded, preferably between 160 and 180 nm.
• the functionalization method according to the invention comprises a first step of providing a device as shown in FIG. 1, followed by a step of hydration of at least one surface of the fluidic vein of the device.
• the hydration step comprises immersing the device provided with the fluidic veins 1 in a solution that enters the veins through the fluidic accesses E and S.
• This solution is an aqueous or alcoholic aqueous solution with basic or acidic pH .
• the device is left in the solution for 1 hour and then it is washed with pure water and dried with nitrogen. Alternatively, a plasma 02 can be used.
• the thus hydrated device is subjected to a silanization step.
• the silanization step comprises immersing the device in a solution containing 10 mM photosensitive silane which penetrates and "lines" the interior of the channels through the fluidic ports.
• the device is immersed in a solution containing trichlorethylene, and incubated for a period of 6 to 48 hours, on average of about 12 hours at room temperature. After washing in the silanization solvent (trichlorethylene for example), then ethanol, the device is dried under nitrogen.
• the silanization solvent trichlorethylene for example
• the silane covers all the surfaces of the device, unless protective zones are provided on these surfaces by means of a material preventing silanization.
• the silane used is a photosensitive oxyamine silane whose synthesis and formulation is described below:
• the silanized device is subjected to a photodeprotection step.
• This photodeprotection step comprises contacting at least one surface of the device with an aqueous solution of 5% pyridine or an aqueous solution of 20 mM sodium hydroxide.
• this solution is confined in the fluidic vein to prevent or limit its evaporation.
• this confinement is obtained by closing the accesses E and S.
• device is thus mounted on the tray of a microscope, equipped with a mercury lamp 100 having preferably a power of 100 W and an intensity of between 20 and 25 mW / cm 2 , preferably 24 mW / cm 2 .
• the lamp 100 is intended to irradiate the silane layer and in particular that contained in the fluidic veins 1b.
• the thickness of the wall comprising the silicon layer covering the fluidic vein is sufficiently thin (in this case between 100 and 200 nm excluded, preferably between 160 and 180 nm), and chosen judiciously to allow the transmission a portion of light ray so that sufficient insolation energy passes through this part of the wall.
• the irradiation of the silane causes deprotection and activation of the function that this silane comprises, and which is intended to fix a probe 1 10 (see FIG. 14).
• FIG. 2 illustrates the device of the invention during a sequential insolation.
• the fluidic vein 1b where it is desired to graft the probes is sequentially insolated by a UV flash 100 which is emitted and whose beam passes freely through a mechanical opening 101 of adjustable width (diaphragm + shutter ).
• Each flash occurs after moving the tray on which the device rests.
• the size of the exposed spots 120 depends on the width of the mechanical opening, and is advantageously of the order 100 ⁇ m in diameter but can be reduced more if necessary. Spot size may vary from site to site, and if necessary will require adjusting the flash aperture.
• FIG. 3 illustrates the device of the invention during a sequential insolation with a mask of opaque patterns 130.
• These patterns are defined in a material that is opaque to the irradiation wavelengths of the silane.
• This mask 30 locally covers the wall V having a thickness between 100 and 200 nm excluded, preferably between 160 and 180 nm, and comprising the silicon layer.
• This mask 130 is structured by thin layer deposition techniques and chemical or dry etching. It is for example to have patterns of chrome, gold, or other material on the wall 1 '. The only condition is that the mask material is opaque to the irradiation wavelengths of the silane and that its thickness prevents any transmission of UV energy from silane deprotection.
• This material can also take on functions of an electrical nature (for example, electrodes for DEP concentration, piezometallic detection electrodes, etc.).
• an electrical nature for example, electrodes for DEP concentration, piezometallic detection electrodes, etc.
• FIG. 4 illustrates a device according to the invention during a sequential insolation with a photolithography mask 140.
• the sequential insolation can be done using the UV lamp 100 alone or by coupling this lamp and the microscope with the use of a quartz photolithography mask 140 covered with chrome patterns 141, of micron size (of the order of one micrometer or more) or even submicron, which thus filter the UV light.
• the microscope is equipped with a mask holder that is affixed and aligned above the sample holder (taking up the same principle than that of photolithography in conventional microelectronics processes). Between each UV flash, the mask gate is moved in X, Y (in the manner of a "stepper" or photorepetitor) by a value that depends on the location of the sites to be insolated in the fluidic vein.
• This latter method can be coupled to the use of opaque masks 130 structured on the device (FIG. 3) which have a smaller size or spacing than the patterns of the photolithography mask. Such a combination is shown in FIG.
• the two advantages of such a combination are the use of lower resolution masks 130 which is less expensive and the reduction of the area covered by the opaque patterns. Indeed, in the case of sensors or part of the peripheral wall 5 can be vibrated (see Figures 10 to 14) the presence of said patterns can generate a degradation of the resonance frequency (and therefore a decrease in sensitivity) because they weigh down the wall. In addition, it allows to retain only the reasons fulfilling a function of electrical, mechanical, chemical, specific to the device.
• the opaque layer when it is a metal (for example gold, AISi, chromium, nickel, tungsten, etc.) can serve as a piezometallic track to perform a piezometallic detection. associated with the gravimetric sensor, rather than a capacitive detection for example. In this case, it is necessary to structure a metal layer above the wall of the gravimetric sensor.
• the insolation can be made simultaneously on the entire surface that is to be functionalized. This insolation is said in "full plate”.
• the full plate insolation is made through a photolithography mask 140.
• units 130 are deposited and structured in an opaque material with respect to the irradiation wavelengths of the silane.
• This material (chromium, gold, or other material) is directly integrated on the device and locally covers the wall 1 'provided with the silicon layer 5a and having a thickness between 100 and 200 nm excluded, preferably between 160 and 180 nm. The entire plate is insolated at one time allowing the deprotection of silanes 120 which are not located below the opaque patterns deposited on the wall of the fluidic vein.
• Full plate insolation enables the device to be insolated at one time, in order to radiate all the areas of interest collectively, and not to resort to multiple insolations of the silane, as is the case for sequential insolation. This process is therefore faster.
• the device After UV irradiation, during the grafting step, the device is rinsed with water and is brought into contact with an aqueous solution containing the molecule to be grafted.
• the methods of grafting by specific reaction are preferred, that is to say that the immobilization of the probe on the deprotected silanes implements a pair of chemical functions carried on the probe and the deprotected silane is fixed. on the surface of the fluidic vein.
• This notion of a pair of chemical functions is based on the reactivity between a nucleophile and an electrophile, for example.
• the grafting takes place only where the silane, covering the device, has been previously irradiated and thus deprotected.
• the immobilization therefore establishes covalent type bonds between the deposited probe 10 (oligonucleotide sequence with associated chemical function) and the irradiated silane.
• the grafting of oligonucleotides is carried out by immersion of the device in an oxidized periodate sodium solution containing the oligonucleotides to be fixed (comprising vicinal diol functions at the 3 'or 5' ends or comprising a 3 'ribose) at 20 ⁇ 15 minutes at room temperature. The device is then rinsed with water and then dried under a stream of nitrogen.
• FIGS. 8 and 9 respectively illustrate a device according to the invention during the probe fixing step inside the fluidic vein after sequential insolation with a photolithography mask 140 (not shown) or after sequential insolation with the mask 130 of opaque patterns.
• the method according to the invention comprises a subsequent step of hybridization.
• the device is brought into contact with a solution containing the targets (for example complementary sequences of oligonucleotides) present in a concentration equivalent to 100 nM, labeled with a fluorophore Cy3®.
• the immersion time of the device is one hour at 39 ° C.
• the device is then rinsed in a buffer solution: 2X SSC (Sigma Aldrich).
• This hybridization step is followed by a fluorescence read step.
• a fluorescence read step For example, a GeneTAC TM LS IV brand scanner, genomic solutions (Cy3 emission wavelength: 570nm, Cy3 excitation wavelength: 550nm) can be used.
• the liquid can penetrate freely in the fluidic veins through the fluidic accesses E and S.
• a device may be a sensor for gravimetric detection.
• a device is shown in FIGS. 10 and 11, and comprises a planar electromechanical oscillator 1 comprising a square bottom 1 and flanks 1c defining a through cavity 1b.
• Oscillator 1 thus comprises a fluidic vein 1b.
• an electrode 2a, 2b, 2c and 2d is disposed in the same plane as the oscillator.
• the electrodes are opposite the sides of the oscillator, parallel to its bottom and substantially the same thickness.
• the distance g must be as small as possible, its value being limited mainly by the resolution of the lithography tools as well as by the thickness TSQ of the plate 1 in which the oscillator 1 is etched (typically g is of the order of TSQ / 30 and greater than 100 nm).
• the wall 1 d is shown the wall 1 d, opposite the bottom 1a.
• the set of walls 1a, 1c and 1d constitute the peripheral wall 5 of the fluidic vein 1b.
• the wall 1d comprises at least partially a silicon layer 5a, and has, at least locally, a thickness of between 100 and 200 nm excluded, preferably between 160 and 180 nm.
• the oscillator 1 is supported by support means over an opening 3a (see FIG. 12) so that it can vibrate, preferably at its resonant frequency (according to a lamé, or volumetric extension for example), substantially in its plane, by electrostatic coupling through the side electrodes.
• the gravimetric detector according to the invention has a high coefficient of quality since the volume of displaced fluid is located inside the fluidic vein of the oscillator.
• the device further comprises a fluid passage channel 4 arranged to be in fluid communication with the through cavity 1b of the oscillator 1.
• the fluid enters the device through a fluidic inlet E, through the cavity 1b of the oscillator 1 and then out of the device by the fluidic outlet S.
• the fluid analyzed by the device is sealed from the environment in which the oscillator is actuated and which is, preferably, a dry medium.
• the planar electromechanical oscillator is in the form of a plate with a width L sq and a thickness T sq such that the ratio L sq / T sq of the width over the total thickness of the The oscillator is between 10 and 30, preferably 30. In this way, the plate exhibits a vibratory behavior different from a membrane.
• the support means are distributed at the four vertices of the oscillator. They can be in the form of massive pieces such as blocks 6 and pairs of arms 7, as illustrated in FIG. 1. In this figure, it can be seen that the two pieces 6 and respectively the two pairs of arms 7 are in the extension of the diagonals of the oscillator 1. Said pairs of arms are machined so as to allow the circulation of fluid within the through cavity 1b passing through the oscillator 1.
• the actuating means are implemented and arranged relative to the oscillator so that it can enter vibration in its plane, according to a specific vibration mode.
• the oscillator may vibrate according to different modes, such as the Lamé mode, the volumetric expansion mode or, according to the so-called “wine glass” mode (particularly for a circular or annular oscillator).
• the oscillator 1 can be vibrated, in its plane, by electrostatic coupling, via at least one of the four electrodes 2a to 2d, or, in a preferred embodiment, two adjacent electrodes.
• actuation means may, however, be integrated on oscillator 1 by structuring, for example, a layer of piezoelectric nature (aluminum nitride or PZT for example) on the surface external of the upper wall 1d of the oscillator, it is possible to carry out a piezoelectric actuation.
• a layer of piezoelectric nature aluminum nitride or PZT for example
• the detection of vibration amplitudes of the oscillator can be done by capacitive coupling via at least one of the four electrodes 2a to 2d, or, in a preferred embodiment, two adjacent electrodes.
• Other detection means may be envisaged, such as a piezoelectric, piezometallic or piezoresistive detection.
• a substrate which may consist either of a layer of polysilicon deposited on a thermal oxide, or of an SOI (Silicon On Insulator) substrate. This latter substrate consists of two monocrystalline silicon layers between which is disposed a layer of silicon dioxide (SiO 2).
• the realization of a gravimetric detection device comprises, in a general manner, the following steps:
• a substrate suitable for the gravimetric detection envisaged comprising, at least partially, a layer of silicon
• the embodiment of a through cavity in said oscillator such that the wall of the oscillator comprising at least partially the silicon layer has, at least locally, a thickness e of between 100 and 200 nm excluded, preferably between 160 and 180 nm, the realization of a channel for the passage of the fluid, said channel being in fluid communication with said fluidic vein formed in the oscillator,
• FIG. 12 An exemplary embodiment of a device is illustrated in section in Figure 12, in cross section.
• the device comprises an oscillator 1 of total thickness T S Q, between two cavities 3a and 3b.
• the cavity 3b is defined between the oscillator 1, a transparent cap 50 (preferably glass or Pyrex) or a cover support layer 60 (biocompatible polymer or highly resistive silicon).
• the device may also comprise a layer 71 of metal to form electrodes (see Figure 14).
• the portion of the wall 1a and / or 1d has at least locally a thickness e of between 100 and 200 nm excluded, preferably between 160 and 180 nm.
• These walls comprise a silicon layer 5a issuing from the layer 21 (or 31: see FIG. 14) of the SOI substrate used during the manufacture of the device.
• An example of manufacture is given in document FR 2 931 549.
• the advantage of providing walls 1a and 1d having a thickness between 100 and 200 nm excluded, preferably between 160 and 180 nm lies in the possibility of functionalizing the inner face of the oscillator after the manufacture of the device, and not necessarily when of this manufacture as suggested in document FR 2 931 549.
• the invention therefore makes it possible to propose silicon oscillators which can be further functionalized as required.
• pillars may be arranged upstream and / or downstream of the cavity 1b machined in the oscillator (that is to say before and / or after the passage of the arms 7 indicated in FIG. 13). . Upstream of the oscillator, they can be used to capture molecules that are not of interest and that are brought by the fluidic inlet E. For this, the spacing between these pillars is adjusted so as to let flow from the input E to the output S the molecules of interest but not the other molecules. Placing pillars downstream of the oscillator makes it possible to reverse the flow direction of the fluid and thus to facilitate the use of the detection device according to the invention which does not depend on the flow direction of the fluid.
• the pillars When the pillars are integrated in the oscillator, they serve to support and strengthen the wall 1d covering the cavity 1b formed within the oscillator. They are also used to increase the capture area available for grafting biological objects of interest, in order to increase capture probability and sensor sensitivity.
• the pillars have a cross section of circular, elliptical or polygonal shape.
• Figure 14 shows a device in longitudinal section, similar to Figure 12 and whose inner face of the cavity of the oscillator has been functionalized by the method according to the invention.
• This device comprises, above the functionalized wall of the oscillator, a metal layer 71 serving as a mask during the functionalization, and advantageously to electrical functions, such as concentration by DEP (dielectrophoresis) or piezoelectric detection.
• DEP dielectrophoresis

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  • 2011-06-29 US US13/805,491 patent/US8968673B2/en active Active
  • 2011-06-29 EP EP11738320.8A patent/EP2588405A1/de not_active Withdrawn
  • 2011-06-29 WO PCT/IB2011/052865 patent/WO2012001642A1/fr active Application Filing

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