liquid analysis device

Abstract

The invention relates to an analysis device for biological analysis with a view to detecting the presence and / or concentration of a species in a liquid contained in an analysis chamber of a cartridge. The analysis device comprises in particular piezoelectric vibration means provided with a disengageable piezoelectric finger. Figure 11

Description

Title of the invention: device for analyzing a liquid FIELD OF THE INVENTION

[0001] The technical field of the invention is that of biological analysis with a view to detecting the presence and / or the concentration of a species (an analyte) in a liquid, in particular a biological liquid. The invention relates more particularly to an analysis device configured to cooperate with an analysis cartridge provided with a chamber in which there is a liquid to be analyzed. TECHNOLOGICAL BACKGROUND OF THE INVENTION

[0002] Document EP3447492 discloses a method for capturing and detecting a species, often referred to as an “analyte”, in a liquid, in particular a biological liquid. The principles of capturing and detecting patterns implemented by this method are also set out in the article by Fratzl et al “Magnetophoretic induced convective capture of highly diffusive superparamagnetic nanoparticles”, Soft Matter, 14. 10.1039 / C7SM02324C.

[0003] This method comprises in particular a step which consists of mixing a sample, formed of a liquid to be analyzed, with magnetic particles. These particles have, in this respect, a nanometric or more generally submicrometric size, and are coupled to capture elements capable of binding specifically to the species to be detected and / or quantified. This species, the analyte, can be an antigen and the element an antibody, but the reverse configuration is also possible.

[0004] During this step, detection elements are also introduced into the sample. The detection elements may in particular comprise an antibody or a detection antigen carrying a photoluminescent marker, for example a fluorescent marker.

[0005] At the end of this step, complexes formed of the capture element, the species, and the detection element are thus formed in the solution. These complexes are then immobilized on a support comprising magnetic micro-sources ordered according to a determined spatial pattern. The pattern is defined by areas of strong magnetic field and areas of weak magnetic field inducing significant magnetic field gradients. The complexes carried by the magnetic particles tend to agglomerate on the support at the level of the areas where the magnetic field norm is maximum. Photoluminescent markers (and in particular fluorescent markers) make it possible to make the determined spatial pattern visible, which indicates the presence of the analyte in the solution. The average intensity (spatially) of this light pattern is usually referred to as the “specific signal”.

[0006] In most cases, and particularly when the analyte is absent from the sample or when its quantity is limited in the sample, the unbound detection elements carrying the photoluminescent labels remain dispersed in suspension in the solution. They contribute to forming a relatively homogeneous luminous background. The average intensity (spatially) of this luminous background forms a signal called the "supernatant signal". In addition to the unbound photoluminescent labels, this luminous background also consists of the luminous intensity emitted by all the photoluminescent materials in the sample. The capture elements not bound to the analyte and to the detection element are also immobilized on the support, but since they do not carry labels, they do not contribute to the luminous pattern or to the luminous background.

[0007] The spatial ordering in the plane of the support of the micro-sources of magnetic field and the light intensity of the patterns made apparent by the photoluminescent markers make it possible to carry out detection and quantification of the analyte in the sample without washing, that is to say without removing the liquid solution after having immobilized the complexes on the surface of the support, which is particularly advantageous. To enable this detection, the sample and the surface of the support are illuminated to enable the detection of the photoluminescent markers and a digital image is acquired. This digital image therefore has a spatially variable intensity (in the plane of the image) depending on the intensity of the magnetic field produced by the support.The image is processed to identify this spatial variation, and to determine the specific signal and the supernatant signal, and the specific signal / supernatant signal ratio makes it possible to conclude on the presence of the analyte in the sample or even to estimate its concentration.

[0008] The simplicity of this approach, and in particular the absence of a washing step, allows its integration into an autonomous, portable or transportable immunological analysis device "at the patient's bedside", in the field and without a pump or valve, whereas traditionally this type of analysis is carried out in a central laboratory.

[0009] To enable the application of the detection method, the biological liquid is introduced into a cartridge, for example a single-use cartridge, comprising a plurality of analysis chambers, this cartridge being intended to be introduced into the analysis device. The plurality of analysis chambers makes it possible to conduct several analyses from a sample of biological liquid, each analysis being able to be independently conducted on samples respectively held in each of the chambers.

[0010] The cartridge comprises a liquid discharge opening, a plurality of vents arranged downstream of the analysis chambers and a network of channels for fluidically connecting the opening to the analysis chambers. The liquid sample biological fluid discharged into the opening spreads by capillary action in the network of channels to fill the chambers.

[0011] The implementation of this cartridge, although undeniably presenting numerous advantages, requires a number of manipulations which it is desirable to reduce.

[0012] Furthermore, this implementation also requires ensuring effective dissolution and mixing of the magnetic particles and / or detection elements.

[0013] An aim of the present invention is to provide an analysis device making it possible to implement effective mixing of the magnetic particles and / or detection elements present in an analysis chamber of an analysis cartridge. BRIEF DESCRIPTION OF THE INVENTION

[0014] The object of the present invention is achieved by an analysis device for biological analysis with a view to detecting the presence and / or concentration of a species in a liquid which comprises:

[0015] - a support for receiving at least one analysis cartridge so that said analysis cartridge rests on said support by one of its faces, and which comprises an essentially flat rear face, and merged with an XY plane, said analysis cartridge comprising at least one chamber capable of containing a liquid intended to be analyzed;

[0016] - piezoelectric vibration means provided with a piezoelectric finger, said piezoelectric finger extends between two ends called, respectively, first end and second end, the piezoelectric vibration means being arranged so that the piezoelectric finger can adopt one or the other of two positions called, respectively, engaged position and disengaged position, the engaged position being a position for which the second end is in abutment against the support or the rear face when the analysis cartridge rests on the support, while the disengaged position is a position for which the second end is at a distance from the support and the rear face so as to allow the withdrawal of the analysis cartridge;

[0017] - engagement means configured to allow passage of the piezo finger electrically between one of the engaged position and the disengaged position to the other of these two positions, the engagement means involving a translational movement or a pivotal movement.

[0018] According to one embodiment, the piezoelectric finger is configured to impose a vibration on the rear face as soon as the second end is pressed against the rear face.

[0019] According to one embodiment, the piezoelectric finger is configured to exert, against the rear face, a bearing force perpendicular to the XY plane when it is located in its engaged position.

[0020] According to one embodiment, said analysis device comprises complementary magnetic means intended to impose a complementary magnetic field in the at least one chamber of the analysis cartridge.

[0021] According to one embodiment, said analysis device further comprises means for analyzing the liquid likely to be present in the at least one chamber.

[0022] According to one embodiment, the analysis means comprise a detector and a radiation source configured to analyze a liquid likely to be present in the analysis chamber.

[0023] According to one embodiment, the support is perforated so as to make the rear face of the analysis cartridge accessible via the second end when said cartridge rests by its rear face on said support.

[0024] According to one embodiment, said device comprises loading means cooperating with the support and configured to impose on said support one or the other of an analysis position and a loading position, the loading position being a position allowing the installation and / or removal of the analysis cartridge from said support, while the analysis position is a position allowing the piezoelectric finger to be engaged against the rear face of the analysis cartridge, advantageously the loading means comprise a worm screw.

[0025] According to one embodiment, the analysis position is also a position allowing the analysis of the fluid contained in the chamber by the analysis means.

[0026] According to one embodiment, the piezoelectric finger is mounted on a lever.

[0027] According to one embodiment, the piezoelectric vibration means com take a hollow cylindrical body which forms with the piezoelectric finger a piston, called a piezoelectric piston, the piezoelectric finger being partially housed, coaxially with said hollow cylindrical body, in the hollow cylindrical body and partly opening through an opening in said hollow cylindrical body, the piezoelectric vibration means further comprise a guide cylinder, in which the hollow cylindrical body is partially housed in sliding connection.

[0028] According to one embodiment, the engagement means comprise a cam linked to a shaft, and acting on the hollow cylindrical body to impose a translational movement on it in the direction of elongation of the piezoelectric finger, the shaft is advantageously controlled in rotation by means of a motor, in particular a stepping motor.

[0029] According to one embodiment, the piezoelectric vibration means comprise a suspension mechanism configured so that the piezoelectric finger, when in its engaged position, imposes a predetermined contact force on the rear face.

[0030] According to one embodiment, the suspension mechanism comprises a spring mounted in compression and bearing on the one hand against the hollow cylindrical body and on the other hand against a shoulder of the piezoelectric foot.

[0031] According to one embodiment, the shaft is mounted to rotate around an axis perpendicular to the direction of elongation of the piezoelectric finger.

[0032] According to one embodiment, the support comprises shims configured to force the rear face of the analysis cartridge to coincide with the XY plane.

[0033] According to one embodiment, the analysis device comprises additional means for holding the analysis cartridge on the support, these additional holding means are in particular configured to hold the analysis cartridge at the vents of said cartridge and communicating with the chamber, the additional holding means are also configured to close said vents. Brief description of the drawings

[0034] Other characteristics and advantages will appear in the following description of an analysis cartridge and an analysis device according to the invention, given as non-limiting examples, with reference to the appended drawings in which:

[0035] [Fig-1] [Fig.l] is a schematic representation, in perspective, of a analysis cartridge capable of being implemented according to the principles of the present invention;

[0036] [Fig.2] [Fig.2] is a schematic representation of the fluidic section according to a section plane of said fluidic section parallel to the upper face, [Fig.2] represents in particular the at least one analysis chamber in fluidic communication on the one hand with the opening via the channels and on the other hand with the at least one vent via the at least one vent channel;

[0037] [Fig.3] [Fig.3] is a schematic representation of the cartridge shown in [Fig.l] in perspective and exploded view;

[0038] [Fig.4a] [Fig.4a] is a schematic representation along a transverse sectional plane (perpendicular to the main faces) of the cartridge of [Fig.l] at the level of the at least one analysis chamber;

[0039] [Fig.4b] [Fig.4b] is another schematic representation according to a transverse section plane (perpendicular to the main faces) of the cartridge of [Fig.l] at the level of the at least one analysis chamber, said cartridge implementing a non-magnetic layer;

[0040] [Fig.4c] [Fig.4c] is a perspective representation of an interlayer film that can be used for assembling the cartridge of [Fig.l];

[0041] [Fig.4d] [Fig.4d] is a schematic representation in top view of a detection pattern defined by the magnetization produced by a magnetic layer embedded in the support of a cartridge, the magnetic field present in an analysis chamber and the standard of this field;

[0042] [Fig.5] [Fig.5] is a schematic representation of an analysis chamber filled with a liquid which comprises in suspension the analysis, the magnetic nanoparticles onto which capture agents and detection agents are grafted, [Fig.5] illustrates in particular the mechanism of formation of the complexes;

[0043] [Fig.6] [Fig.6] is a representation of an analysis device implemented according to the principles of the present invention;

[0044] [Fig.7a]

[0045] [Fig.7b] Figures 7a and 7b are representations of the interior of the analysis device of [Fig.6], the finger of the piezoelectric vibration means being in a disengaged position, [Fig.7b] being a sectional view;

[0046] [Fig.7c] [Fig.7c] is a representation of the interior of the analysis device of [Fig.6], the finger of the piezoelectric vibration means being in an engaged position;

[0047] [Fig.8] [Fig.8] illustrates, in a perspective view, a support capable of being implemented within the framework of the present invention, in particular, the support shown in this figure can accommodate two analysis cartridges;

[0048] [Fig.9] [Fig.9] is an illustration of the support of [Fig.8] and accommodating on one of its sites an analysis cartridge;

[0049] [Fig. 10] [Fig. 10] is an illustration of a piezoelectric finger that can be implemented in the context of the present invention;

[0050] [Fig. 11] [Fig. 11] is a representation, according to a sectional plane along the elongation axis of the piezoelectric finger, of piezoelectric vibration means according to an advantageous embodiment of the present invention;

[0051] [Fig. 12] [Fig. 12] is a representation, in a perspective view, of a hollow cylindrical body implemented in the piezoelectric vibration means of [Fig.11];

[0052] [Fig. 13] [Fig. 13] is a representation, in a perspective view, of a guide cylinder implemented in the piezoelectric vibration means of [Fig. 11]. DETAILED DESCRIPTION OF THE INVENTION

[0053] [Fig.l] represents an analysis cartridge 1 for the analysis of a species (hereinafter “analyte”) likely to be present in a liquid, and more particularly a biological liquid.

[0054] The analysis cartridge 1 is, in this regard, adapted to receive a sample of a liquid, for example a biological liquid, in order to detect the presence of an analyte given in said liquid.

[0055] The analysis cartridge 1 thus comprises at least one microfluidic analysis chamber 5. In particular, the analysis cartridge may comprise between 1 and 10, for example 5, analysis chambers 5. It is understood that an analysis chamber may itself comprise a plurality of housings arranged in series. The remainder of the statement of the present invention will nevertheless be limited to the description of a chamber having a single housing and designated by the word "chamber".

[0056] The analysis cartridge 1 may comprise a gripping end allowing it to be handled. The gripping end 1a may carry a label, for example provided with a bar code or a two-dimensional code, allowing identification and traceability of the analyses carried out using the analysis cartridge 1 in question. The identification means may alternatively comprise an “RFID” chip.

[0057] The analysis cartridge 1 also comprises an active section 1b formed, for example, in the extension of the gripping end 1a.

[0058] The active section 1b is generally planar in shape and comprises two main faces called, respectively, the upper face and the lower face.

[0059] The analysis cartridge 1 may comprise at least one pouring opening 2 which allows the introduction of a liquid into the analysis cartridge 1. This opening 2 opens in particular onto the upper face of the active section 1b.

[0060] The opening 2 is in particular in fluid communication with the at least one analysis chamber 5. In particular, the active section comprises at least one microfluidic channel 4 ensuring fluid communication between the opening 2 and the at least one analysis chamber 5. In other words, the at least one microfluidic channel 4 ensures the flow and distribution of the liquid poured into the opening 2 towards the at least one analysis chamber.

[0061] The analysis cartridge 1 may also comprise at least one vent 3 in fluid communication with the at least one analysis chamber 5 (FIGS. 1 and 2). The at least one vent 3 is in particular configured to allow evacuation of air likely to be present in the at least one analysis chamber 5 during the filling of the latter with liquid. In particular, the fluid communication between the at least one analysis chamber 5 and the at least one vent 3 is ensured by at least one vent channel 4'.

[0062] Thus, in operation, a liquid sample is introduced, for example by means of a pipette, into the opening 2. The sample then flows into the at least one analysis chamber 5 via the at least one microfluidic channel 4. The air likely to be present in the at least one analysis chamber 5 is expelled during the flow of the liquid in said analysis chamber 5 towards the at least one vent 3.

[0063] In the case of a plurality of analysis chambers 5, the microfluidic channels 4 can be arranged so that the flow of the liquid sample is simultaneous in each of the chambers 5 or sequential. By "sequential flow" is meant a filling of the analysis chambers 5 according to a predetermined order. In particular, according to this principle, the flow in a given chamber only begins when the analysis chamber which precedes it in the filling order is completely filled.

[0064] Still in the case of a plurality of analysis chambers 5, it is also possible to provide that the analysis cartridge comprises a plurality of openings, for example an opening dedicated to each chamber of the cartridge.

[0065] The analysis cartridge 1 shown in [Fig.l] may further comprise a reservoir 2' surmounting the opening 2 whose volume equals that of the microfluidic network formed by the at least one microfluidic channel 4, the at least one analysis chamber 5 and the at least one vent channel 4'. In this respect, this volume may be between 5 mm3 and 500 mm3, and more precisely between 20 mm3 and 100 mm3.

[0066] Equivalently, the at least one vent 3 is surmounted by a peripheral wall in order to retain an excess volume of liquid, according to the principle of communicating vessels. Advantageously, the peripheral wall has a height at least equal to the height of the reservoir 2' in order to prevent the liquid from escaping from the analysis cartridge 1. This arrangement makes it possible to limit problems of sanitary origin, or even damage to an analysis device (described in the remainder of the statement) in which the analysis cartridge 1 is intended to be inserted.

[0067] By way of illustration, the analysis cartridge 1 may have a dimension of between 2 cm and 10 cm in width and length, and have a thickness of between 4 mm and 10 mm. The at least one analysis chamber 5 may have a volume typically of between 1 mm3 and 50 mm3 to receive the sample, advantageously between 5 mm3 and 25 mm3.

[0068] According to a non-limiting example shown in [Fig.3], the analysis cartridge 1 can be formed of a support 6 and an upper cover 7 covering the support 6. The support 6 and the upper cover 7 are in particular assembled to each other by placing their so-called “main” surfaces opposite each other.

[0069] The at least one analysis chamber 5, the at least one microfluidic channel 4 and the at least one vent channel 4' form a microfluidic network of the analysis cartridge 1. This microfluidic network is notably defined by recesses formed on the main surface of the support 6 and / or on the main surface of the upper cover 7, that is to say on one and / or the other of the faces of these two elements which are intended to be assembled to each other.

[0070] Each channel 4, 4' is delimited, on the one hand, by the main surfaces of the support 6 and of the cover 7 forming, respectively, a bottom and a vault, and on the other hand, by side walls connecting the bottom and the vault. The distance separating the bottom and the vault of a 4, 4' channel defines a channel height, while that separating two facing side walls defines a channel width. The vault, the bottom and the side walls generally form the walls of the chamber.

[0071] Equivalently, the at least one analysis chamber 5 is also delimited by the main surfaces of the support 6 and the cover 7 forming, respectively, a chamber bottom 5a and a chamber vault 5b (Figures 4a and 4b). The at least one chamber 5 further comprises chamber side walls 5c which extend from the chamber bottom 5a towards the chamber vault 5b. It is however understood that the at least one analysis chamber 5a may be devoid of a vault, and for example form an open well at the level of the active section.

[0072] It is also understood that the side walls of the at least one chamber may be deformable.

[0073] The upper cover 7, at least for the part which overhangs the at least one analysis chamber 5, may be formed from a material transparent to a photoluminescence signal capable of being emitted by detection agents described in the remainder of the statement. The material forming the upper cover 7 may comprise at least one of the materials chosen from: a plastic material for example based on polycarbonate, cycloolefin copolymer or polystyrene, glass.

[0074] The outer surface of the cover 7 can be optically polished at least in line with the at least one analysis chamber 5.

[0075] The microfluidic network, such as that shown in [Fig.2], therefore extends in the main plane of the analysis cartridge 1. It is of millimetric dimension, that is to say that the width of the channels 4, 4' and of the analysis chambers 5 is typically between 0.1 mm and 10 mm. The height of these elements, that is to say the distance separating the bottom of a vault, is also between 0.1 mm and 10 mm. The liquid likely to be introduced at the level of the opening 2 spreads in the microfluidic network by capillarity.

[0076] The analysis cartridge 1 according to the present invention may also comprise at least one first cluster 9 adhering to the bottom of the at least one analysis chamber 5 ([Fig.4a]). The at least one first cluster 9 is in particular formed of magnetic nanoparticles 9a held together, and onto which capture agents 9b are grafted ([Fig.5]).

[0077] Alternatively, it may be considered to arrange the at least one first cluster on the vault 5b of the at least one chamber 5. This configuration may in particular facilitate the resuspension (described below) of said first cluster when the latter is subjected to magnetic forces due to the presence of a magnetic layer 6b described in the remainder of the statement.

[0078] A first cluster may advantageously have a volume of between 0.1 pl and 5 pl and advantageously between 0.5 pl and 2 pl.

[0079] By "held together" is meant a set of nanoparticles linked together. This cohesion between the nanoparticles can be direct or indirect. Direct cohesion can in particular be ensured by dry or freeze-dried nanoparticles, while indirect cohesion can be ensured by an encapsulation material. In this respect, the encapsulation material can comprise sugar (trehalose, glucose, etc.) or viscous solutions (for example, Tween), or glycerol.

[0080] Maintaining the nanoparticles together, and in the form of clusters, ensures better stability of the latter over time.

[0081] The implementation of an encapsulation material makes it possible to facilitate the suspension of nanoparticles presented in the remainder of the description.

[0082] The magnetic nanoparticles 9a may be of nanometric size, typically between 25 nm and 500 nm, and preferably between 100 and 300 nm. The magnetic nanoparticles 9a may be of generally spherical shape. The latter have superparamagnetic characteristics and are biocompatible. They may also be covered with a polymer (of the polystyrene type) having a surface treatment which allows them to be functionalized, for example, by proteins of the Ac or Ag type. The controlled quantity of particles is such that their concentration in the volume of the chamber once filled with the liquid to be analyzed is between 106 particles / ml and 1012 particles / ml, advantageously between 109 particles / ml and 1011 particles / ml.

[0083] The capture agents 9b are capable of specifically binding to the analyte likely to be present in the liquid. In this regard, the analyte may be an antigen, while the capture agent 9b comprises an antibody (the reverse configuration is also possible).

[0084] The analysis cartridge 1 may also comprise at least one second cluster 10 adhering to the bottom of the at least one analysis chamber 5 (FIGS. 4a and 4b). The at least one second cluster 10 is in particular formed of detection agents 10a linked together ([Fig. 5]).

[0085] It is understood, without it being necessary to specify it, that the first cluster 9 and the second cluster 10 can form the same cluster. Furthermore, the first cluster 9 and the second cluster 10 can one and / or the other be deposited on a wall of the chamber.

[0086] Advantageously, the first cluster 9 and / or the second cluster 10 is based on a surface energy density associated with a hydrophobic surface. The surface energy density can be determined, as is well known per se, by measuring the contact angle of a drop of water, placed on the surface for which one is looking to measure energy. A high contact angle, greater than 90°, indicates a low surface energy density, and the surface is said to be hydrophobic. Conversely, a contact angle less than 90° indicates a high surface energy density and the surface is said to be hydrophilic. Considering a hydrophobic surface makes it possible to impose a relatively spherical shape on one and / or the other of the first cluster and the second cluster.

[0087] A second cluster may advantageously have a volume of between 0.1 pl and 5 pl and advantageously between 0.5 pl and 2 pl.

[0088] The at least one first cluster 9 and the at least one second cluster 10 are both intended to allow, respectively, a capture, or even an immobilization, of an analyte 11 present in a liquid, and to detect, or even quantify, the presence of said analyte 11. To this end, the analyte 11 present in a liquid, and in the presence of detection agents 10a and magnetic nanoparticles 9a onto which the capture agents 9b are grafted, forms complexes 12 with these elements ([Fig.5]).

[0089] Magnetic nanoparticles are intended to isolate the complexes, while detection agents allow them to be detected.

[0090] Thus, the implementation of the analysis cartridge 1 for the detection and / or quantification of an analyte in a liquid involves pouring a sample of said liquid into the at least one analysis chamber via the opening 2.

[0091] The formation of the complexes 12 also requires suspending, in the liquid sample present in the analysis chamber 5, the elements forming the first cluster 9 and the second cluster 10.

[0092] This suspension may in particular comprise a separation of the first and second clusters from the chamber bottom 5a as well as a separation of the elements from each other in order to disperse them in the sample. For this purpose, piezoelectric vibration means 110 described in the remainder of the statement may be implemented.

[0093] These piezoelectric vibration means 110 are in particular adapted to impose a vibration on the bottom of the chamber 5 a. This vibration makes it possible to generate an acoustic pressure field in the liquid present in the analysis chamber 5, and thus to suspend the elements forming the first cluster 9 and the second cluster 10.

[0094] According to a first variant, the vibration can be imposed at fixed frequencies, for example between 5 KHz and 2 MHz, advantageously between 20 KHz and 200 KHz. Still according to this first variant, the vibration can be close to a resonance frequency of the analysis chamber 5 (by “close to the resonance frequency”, we mean a frequency at + / - 15%, advantageously at + / - 10%, even more advantageously at + / - 5% of the resonance frequency of the analysis chamber). Advantageously, the resonance frequency of the analysis chamber 5 is of the order of 50 KHz, or of the order of 80 KHz or of the order of 110 KHz.

[0095] An analysis chamber having such resonance frequencies may comprise, along a section plane perpendicular to the rear face of the cartridge, a rectangular section terminated at each of its two ends by a mouthpiece whose section, along the same plane, is triangular. The length and width of the rectangular section are respectively 8.4 mm and 2.4 mm, while the base and height of the triangular section are respectively 2.4 mm and 4 mm. The height of the analysis chamber is 390 qm.

[0096] According to a second variant, the vibration can be imposed in the form of cycles, and for example in the form of repeated cycles. In this regard, a cycle can comprise a sweep in increasing or decreasing frequency, and more particularly a frequency sweep around the resonance frequency of the analysis chamber. The complete frequency sweep can be of a duration of between 10 seconds and 200 seconds. In particular, this frequency sweep comprises an incrementation or a decrementation in steps of the frequency.

[0097] In particular, each step corresponds to maintaining the frequency for a duration which can be between 2 seconds and 10 seconds so as to allow the liquid to move sufficiently for a minimal mixing effect.

[0098] For example, a cycle may involve a frequency sweep from 110 KHz to 120 KHz, or conversely a frequency sweep from 120 KHz to 110 KHz. This sweep may be executed in steps of 1 KHz, and a maintenance, at each step, of the vibration for a duration of a few seconds and in particular 2 seconds.

[0099] Still by way of example, the vibrational sequence may comprise the repetition of an elementary sequence which comprises a first cycle and a second cycle.

[0100] The first cycle may include a frequency sweep from 120 kHz to 111 KHz in 1 kHz steps and maintaining the vibration at each step for 2 seconds.

[0101] The second cycle may comprise a frequency sweep from 110 kHz to 119 kHz in steps of 1 kHz and maintaining the vibration at each step for 2 seconds.

[0102] This elementary sequence can, for example, be repeated from 1 to 4 times.

[0103] It is also possible to consider a vibration at a fixed frequency (for example approximately equal to one of the frequencies chosen from: 56 kHz, 74 kHz, 80 kHz, 110 kHz) continuously or in the form of one or more pulses. The fixed frequency is advantageously equal to, or at least close to, a natural frequency of the analysis chamber (by natural frequency we mean the set formed by the resonance frequency and its harmonics).

[0104] Particularly advantageously, the side walls 5c can be structured so as to create vortices favorable to mixing in the sample. when the latter circulates in the analysis chamber. This structuring of the side walls 5c may include a crenellated surface.

[0105] In a particularly advantageous manner, gas, and more particularly air, is initially trapped in the side wall 5c of the at least one chamber 5.

[0106] The trapped gas can be released under the action of a mechanical stress applied to the at least one analysis chamber and thus generate gas bubbles on the side wall of the at least one chamber as soon as the liquid sample is present in the at least one chamber 5. This mechanical stress can, in particular, be applied to the rear face of the analysis cartridge 1.

[0107] According to an advantageous embodiment, the side walls 5c of the at least one chamber 5 may be made of a porous material. The gas is initially located in the pores of the porous material.

[0108] According to an alternative or complementary embodiment, the gas can be initially trapped in slots 5e opening onto the side walls ([Fig.4c]).

[0109] The 5e slits may have a length of between 100 qm and 1000 qm, and a cross-section whose largest dimension is between 100 qm and 400 qm.

[0110] The cross-section of a slot may comprise at least one of the shapes chosen from: square, rectangle, round.

[0111] According to the present invention, as soon as the gas bubbles are generated (in particular under the effect of the constraint previously described), the acoustic pressure field, generated by vibration of the chamber bottom, makes it possible to vibrate the latter in the liquid present in the analysis chamber.

[0112] These vibrating gas bubbles then act as additional vibrating agents which improve the mixing of the liquid present in the analysis chamber.

[0113] This effect can nevertheless be optimized by requiring the gas bubbles to vibrate at a frequency close to their resonance frequency (by "close to the resonance frequency" is meant a frequency at + / - 15%, advantageously at + / - 10%, even more advantageously at + / - 5% of the resonance frequency of the gas bubbles). Indeed, under these conditions, the contribution of the gas bubbles to the mixture is exacerbated, all the more so since certain bubbles are capable of transmitting energy by their implosion and the resulting shock wave.

[0114] For this purpose, the pores and / or the slots trapping the gas can be configured so that the gas bubbles likely to be generated have a resonance frequency close to that of the analysis chamber.

[0115] In particular, for the specified slit sizes, the bubble sizes may be between 50 qm and 500 qm. For this range of bubble sizes, the frequencies resonance frequencies are between 20 kHz and 500 kHz.

[0116] Still according to the present invention, the analysis cartridge 1 may comprise a magnetic layer 6b ([Fig.4a]) arranged to immobilize the magnetic nanoparticles 9a of the at least one analysis chamber 5 on the bottom of said chamber. It is therefore understood that this magnetic layer also makes it possible to immobilize the complexes 12. The magnetic layer 6b is advantageously micro-structured so that the magnetic nanoparticles immobilized on the bottom of the analysis chamber 5 form a predefined pattern.

[0117] The magnetic layer 6b may in this respect comprise a repeated juxtaposition of at least a first region 6b 1 and a second region 6b2. More particularly, the first region 6b 1 may have a magnetic polarization in a first direction, and the second region 6b2 may have either zero magnetic polarization or magnetic polarization in a second direction different, preferably 180°, from the first direction ([Fig.4a]).

[0118] The support 6 may in particular be arranged so that it comprises, from its main face towards the rear face, an interlayer film 6d, the magnetic layer 6b and a rigid substrate 6a. It is understood that the magnetic layer 6b does not necessarily extend over the entire surface of the substrate 6a (FIGS. 3, 4a and 4b).

[0119] The rigid substrate 6a may comprise a plastic material. The magnetic layer 6b may be arranged on the substrate 6a, or integrated into this substrate, at least at the level of the analysis chambers 5 of the microfluidic network.

[0120] The magnetic layer 6b may comprise magnetic composite materials, such as ferrites, randomly distributed in a polymer or oriented along a pre-orientation axis. This magnetic layer 6b may be similar to a conventional magnetic recording tape. In the latter case, the microstructuring of a magnetic layer is associated with magnetic coding (in particular via a magnetic recording / reading head). More particularly, the microstructuring according to the latter case amounts to creating magnetic zones which may have a different magnetization from one zone to another in terms of orientation and / or amplitude. For example, two adjacent zones may have two opposite orientations, and more particularly at 180°.

[0121] The substrate 6a may also comprise a non-magnetic layer 6c (or a plurality of such films) interposed between the magnetic layer 6b and the interposed film 6d. This non-magnetic layer 6c, which is optional, aims to move the magnetic layer 6b away from the bottom of the analysis chamber 5.

[0122] By “non-magnetic layer” is meant a layer whose magnetic susceptibility is zero or even less than (in absolute value) 103.

[0123] The non-magnetic layer 6c may, for example, comprise a plastic material, such as than polypropylene on acrylic.

[0124] In the example presented above, the interlayer film 6d defines the microfluidic network. In particular, the interlayer film 6d illustrated in [Fig.4c] has a cutout according to a pattern corresponding to the microfluidic network. When this interlayer film 6d is assembled to the substrate 6a to form the support 6, the latter therefore has recesses reproducing the cutting pattern of the film 6d. These recesses, possibly in combination with complementary recesses formed in the upper cover 7, constitute the microfluidic network of the cartridge 1.

[0125] Particularly advantageously, the interlayer film 6d is an adhesive film, also making it possible to assemble and hermetically retain the upper cover 7 to the support 6 at their contacting surfaces, i.e. surrounding the recesses. It may, for example, be a double-sided adhesive film, then simultaneously ensuring its assembly to the substrate 6a, and to the upper cover 7. As is well known per se, such an interlayer film 6d may consist of a strip, for example plastic, the two faces of which are coated with an adhesive material.

[0126] Still advantageously, the gas or air bubbles, when applying a mechanical stress to the bottom of the chamber, can be generated by the release of gas trapped in the interlayer film. Thus, this film can be porous and / or include slits, for example formed when cutting the pattern corresponding to the microfluidic network.

[0127] Returning to the description of the magnetic character of the analysis cartridge, the magnetic layer 6b comprises a succession of polarized regions 6b1 and 6b2 in two different directions (opposite in FIGS. 4a and 4b). As shown in [Fig.4d] which represents a top view of the magnetic layer 6b, the magnetically polarized regions extend in line along a main direction P in the example shown.

[0128] Regions of relatively high magnetic intensity, referred to as attraction zones, are observed at the interfaces between the zones of different polarization. The attraction zones are notably arranged in the form of a plurality of lines Za oriented along the main direction P. The particular arrangement of these lines defines, in combination, a detection pattern.

[0129] It is understood that the in-line arrangement taken as an example only forms a particular case of a detection pattern. An analysis cartridge 1 is more generally provided with magnetically polarized regions defining a well-defined detection pattern, but the configuration of which can be freely chosen.

[0130] The field Bc generated by the magnetic layer 6b as well as its norm are also represented in [Fig.4d]. As will be explained later in this presentation, it may be useful to add an additional (or complementary) external field Bext, to the field produced by layer 6b. [Fig.4d] shows this external field Bext which combines with the field Bc produced by the layer and the norm of this combined field. It is observed that the application of this external magnetic field Bext can lead to the elimination of certain zones of attraction Za produced when only the field provided by the magnetic layer 6b is present. But in all cases, these zones of attraction are arranged according to lines Za oriented along the main direction P, or more generally according to a detection pattern whose characteristics are perfectly determined.

[0131] In the case of an analysis chamber 5 having the dimensions indicated previously, it is possible to envisage forming a detection pattern comprising between 2 and 50 lines, these having a thickness of between 1 pm and 150 pm (advantageously between 5 pm and 30 pm) and separated from each other by a spacing of between 5 pm and 300 pm, advantageously between 25 pm and 150 pm.

[0132] Based on this description, the inventors calculated the surface gradient at the surface of a non-magnetic layer with a thickness of around 55 μm and resting on a magnetic layer.

[0133] The micro magnets of the magnetic layer, on which the non-magnetic layer rests, have a width of 50 pm and a height of 10 pm. These micro magnets have an in-plane polarization and are alternating with each other. In this calculation, a magnetic field source made of NdFeB with a remanence of 1.2T below this magnetic layer is also implemented. The latter imposes a magnetic field with an amplitude between 0.005 Tesla and 0.3 Tesla.

[0134] In the context of this calculation, the inventors were able to demonstrate that the gradients on the surface of the non-magnetic layer are between 50 T / m and 150 T / m, and can be extended to more or less one order of magnitude. These gradients result in a magnetic force exerted on the particles. This force is capable of retaining the magnetic particles (in particular the clusters), and also contributes to the immobilization of the latter (described at the end of this application).

[0135] Thus, when a liquid sample is introduced into the analysis cartridge 1, it flows into the microfluidic channels 4 to fill the at least one analysis chamber 5 and propagate in the vent channels 4'. A vibration as well as a mechanical stress are imposed on the rear face of the analysis cartridge 1. Gas bubbles are then generated by the release of gas under the effect of the mechanical stress. The acoustic pressure field resulting from the vibration imposed on the bottom makes it possible to suspend, and if necessary to mix, the elements forming the first cluster and the second cluster. This acoustic pressure field can, in addition, cause the gas bubbles to vibrate.

[0136] The vibration of the latter contributes, to a certain extent, also to the suspending and mixing the detection agents 10a and the capture agents 9b associated with the magnetic nanoparticles 9a in the liquid sample present in the analysis chamber 5. During the following reaction time, and when the analyte is present in the sample, complexes comprising at least one capture element, at least one magnetic nanoparticle, at least one analyte, and at least one detection element are formed. These complexes are immobilized on the support 6 of the analysis chamber 5 by agglomerating in a preferential manner at the maxima of the magnetic field intensity standard (induced by the micro-sources and possibly the external magnetic field), and therefore to arrange themselves according to the detection pattern defined by the magnetic layer 6b. The excess detection elements remain in suspension in the sample.

[0137] It may be provided that each analysis chamber 5 of a cartridge 1 is prepared to receive capture elements and detection elements of different natures, so as to carry out multiple analyses of a liquid sample introduced into the analysis cartridge 1. It may also be provided that the detection pattern encoded by the portion of the magnetic layer 6b which is arranged at the level of a chamber 5 is different from one chamber to another.

[0138] It is also possible to consider a magnetic layer which comprises a zone devoid of magnetic zones, and at the level of which the first cluster is formed (the re-suspension of the magnetic nanoparticles of the first cluster can thus be facilitated).

[0139] In all cases, the presence of an analyte in the sample retained in an analysis chamber 5 leads to the formation of a detection pattern defined by the magnetic layer 6b.

[0140] The invention also relates to an analysis device 100 intended to cooperate with the analysis cartridge ([Fig.6]).

[0141] The analysis device 100 comprises in particular a support 101 intended to receive at least one analysis cartridge 1 for the purpose of analyzing the liquid sample contained in the at least one analysis chamber 5 (FIGS. 7a to 7c). More particularly, the support 101 is designed to receive the analysis cartridge 1 so that said analysis cartridge 1 rests on said support 101 by one of its faces. In the remainder of the statement, it will be considered that the analysis cartridge rests by its rear face. Nevertheless, this latter aspect is not such as to limit the present invention and a person skilled in the art will be able to consider an analysis cartridge resting by one of its faces opposite the rear face.

[0142] [Fig.8] illustrates in this regard a support 101 capable of being implemented within the framework of the present invention. In particular, the support 101 shown in this figure can accommodate two analysis cartridges.

[0143] The support 101 can also be configured to allow the insertion of an analysis cartridge 1 according to a sliding movement in the direction “A” ([Fig.8]).

[0144] In particular, the support 101 comprises a base, called support base 101a, and side walls 101b and 101c configured to guide the insertion of an analysis cartridge 1.

[0145] Snap-fastening means 102 may also be arranged on the support base 101a. Said snap-fastening means 102 are in particular configured to cooperate with the rear face of the analysis cartridge 1 in order to retain it on the support 101.

[0146] The support 101 is also perforated and comprises a window 103 formed on the support base 101a and intended to make the rear face of the analysis cartridge 1 accessible when the latter is inserted into the support 101. In particular, the window 103 can be arranged directly above the analysis chamber 5 of the analysis cartridge 1 arranged on the support 101.

[0147] The support may, alternatively, be configured to guide the vibrations imposed by the piezoelectric finger. The support may, in this regard, comprise means for distributing the vibrations, imposed by the piezoelectric finger, to the cartridge. These distribution means may in particular be arranged to guide the vibrations at the level of the at least one analysis chamber, and more particularly at the level of each of the analysis chambers when there is a plurality of analysis chambers.

[0148] When it is arranged on the support 101, the analysis cartridge 1 has its rear face which is merged (i.e.: coplanar) with the XY plane. In particular, this XY plane is a plane parallel to the support base 101a. The XY plane can, for example, be horizontal.

[0149] The side walls 101b and 101c further comprise cleats 104 which extend from a free edge of each of the side walls 101b and 101c ([Fig.9])•

[0150] The cleats 104 (or wedges), as well as the snap-fastening means 102 ensure that the analysis cartridge 1 is held on the support 101, and that the rear face of said cartridge 1 and the XY plane are coplanar. These holding means as described are configured to ensure coplanarity of the XY plane and the rear face of the analysis cartridge. The invention is however not limited to the means described alone and those skilled in the art will be able to implement any means ensuring coplanarity of the XY plane and the rear face of the analysis cartridge.

[0151] Spring means may be arranged on the support base 101a. These spring means are in particular configured to press the analysis cartridge 1 against the tabs 104, and thus ensure coplanarity of the XY plane and the rear face of the analysis cartridge. The spring means may comprise levers. However, this latter aspect is not such as to limit the scope of the present invention and those skilled in the art profession may implement any other type of means presenting such functionality.

[0152] The analysis device 100 may also comprise additional means for holding the analysis cartridge on the support. These additional holding means are in particular configured to hold the analysis cartridge at its vents and in particular so as to close said vents. This closing of the vents makes it possible in particular to avoid a pumping effect of the liquid residing in the chamber and consequently to be able to envisage greater vibration amplitudes imposed by the piezoelectric finger. This latter aspect thus makes it possible to envisage shorter mixing times.

[0153] The analysis device 100 also comprises a stop rail. This stop rail is in particular arranged to be opposite a face of the analysis cartridge opposite the rear face. In particular, the stop rail is arranged to limit the movement of the analysis cartridge when the piezoelectric finger is pressing against the rear face. The support may also comprise one or more notches formed on its side walls 101a and 101b allowing contact (called stop) between the stop rail and the analysis cartridge.

[0154] The analysis device 100 also comprises piezoelectric vibration means 110 arranged to impose a vibration at the bottom of the analysis chamber so as to generate an acoustic pressure field in a liquid likely to be present in the at least one analysis chamber 5.

[0155] The piezoelectric vibration means 110 may comprise a transducer, in particular an elliptical transducer of the Elliptec™ transducer type.

[0156] Alternatively, the piezoelectric vibration means 110 may comprise a piezoelectric stack (Piezostack). The piezoelectric vibration means 110 may comprise a so-called Langevin transducer (A Langevin transducer is produced by a stack of ceramics held between two metal parts which ensure clamping of the assembly).

[0157] In this regard, the inventors were able to demonstrate that these linear transducers exhibited good mixing dynamics.

[0158] Bolt-clamped Langevin ultrasonic transducer type transducers are also very efficient.

[0159] In a particularly advantageous manner, the piezoelectric vibration means 110 comprise a piezoelectric finger 111 which extends between a first end 11a and a second end 111b. Generally, the piezoelectric finger may be cylindrical in shape. However, the invention is not limited to this aspect, and those skilled in the art may consider other shapes. It is understood that the second end may be point-shaped, flat, rounded, comprise a plurality of contact points (rake-shaped).

[0160] As illustrated in [Fig.10], the piezoelectric finger 111 may comprise a piezoelectric stack 112 interposed between a first element 113 and a second element 114, both of generally cylindrical shape. The first element 112 extends in particular from the first end 111a towards the piezoelectric stack 112 while the second element extends from the piezoelectric stack 112 towards the second end 111b. It is understood that the first element, the piezoelectric stack and the second element are mechanically integral with each other and in such a way as to ensure a prestress between these different elements. The prestress may be at least 10 times greater than the bearing force exerted by the second end when the latter is bearing against the rear face or the support.In particular, this prestress improves the coupling between the piezoelectric stack and the elements 113 and 114, and thus makes it possible to limit the influence of the support force on the vibration modes of the stack 112. In other words, the prestress can be greater than 20 MPa, advantageously greater than 35 MPa, even more advantageously greater than 50 MPa. The prestress improves the transmission efficiency of the vibrations generated by the piezoelectric finger to the analysis cartridge.

[0161] The piezoelectric vibration means 110 are arranged so that the piezoelectric finger 111 can adopt one or the other of two positions called, respectively, engaged position and disengaged position.

[0162] In particular, the engaged position is a position for which the second end is in abutment against the rear face when the analysis cartridge rests on the support, while the disengaged position is a position for which the contact end is at a distance from the rear face so as to allow the withdrawal of the analysis cartridge 1.

[0163] The transition from one to the other of these two positions may involve a pivoting or translational movement.

[0164] Advantageously, the pressing force exerted by the piezoelectric finger on the rear face is perpendicular to the YZ plane when said finger is in its engaged position.

[0165] The analysis device 100 may also comprise engagement means configured to allow the passage of the piezoelectric finger between one of the engaged position and the disengaged position to the other of these two positions.

[0166] By way of example, and as illustrated in [Fig.7a], [Fig.7b] and [Fig.7c], the piezoelectric vibration means 110 may comprise a lever 110a on which the piezoelectric finger is mounted. More particularly, the lever 110a is rotatably mounted around an axis integral with the analysis device 100. In particular, in [Fig.7a] and in [Fig.7b], the lever 110a imposes on the piezoelectric finger 111 its disengaged position. In other words, the second end 110a of the piezoelectric finger 111 is at a distance from the rear face of the analysis cartridge resting on the support 101. In [Fig.7c], the piezoelectric finger 111 is in its engaged position and therefore has its second end 110b in contact with the rear face of the analysis cartridge 1. According to this aspect, the engagement means may comprise a motor.

[0167] [Fig. 11] illustrates an example of piezoelectric vibration means for which the passage from one of the engaged position and the disengaged position to the other of these two positions involves a translational movement.

[0168] In particular, this example involves a movement of the piezoelectric finger in a direction parallel to its direction of elongation. More particularly, this translational movement may be perpendicular to the XY plane. It is therefore understood, without it being necessary to specify it and according to this last aspect, that the piezoelectric finger may be mounted perpendicular to the XY plane.

[0169] According to the example illustrated in [Fig. 11] and [Fig. 12], the piezoelectric vibration means comprise a hollow cylindrical body 115 which forms with the piezoelectric finger 111 a piston, called a piezoelectric piston. In particular, in this example, the piezoelectric finger 111 is partially housed, coaxially with said hollow cylindrical body, in the hollow cylindrical body 115. In other words, a section of the piezoelectric finger opens through an opening 115a of said hollow cylindrical body 115. It is understood that the section of the piezoelectric finger opening through the opening comprises the second end 111b. The hollow cylindrical body 115 comprises a side wall 115b giving it its cylindrical shape.

[0170] The piezoelectric vibration means further comprise a guide cylinder 116 ([Fig. 11] and [Fig. 13]), in which the hollow cylindrical body is partially housed in sliding connection ([Fig. 11]). In particular, the hollow cylindrical body 115 is mounted in the guide cylinder 116 so that the axis of elongation of the piezoelectric finger coincides with an axis of revolution of the guide cylinder 116.

[0171] Thus, the piezoelectric finger can adopt either the engaged position or the disengaged position by translation of the piezoelectric piston in the guide cylinder and parallel to the axis of revolution of the guide cylinder.

[0172] The passage from one to the other of the engaged position and the disengaged position is, according to the present invention, controlled by the engagement means. In particular, and as illustrated in [Fig. 11], these engagement means comprise a cam 117 linked (in fixed connection) to a shaft 118. In particular, the shaft 118 is rotatably mounted around a fixed axis of the analysis device 100. More particularly, the shaft 118 passes through a wall of the guide cylinder 116 and is configured to drive the cam 117 when it is rotated. In particular, the cam 117 may comprise a cylindrical block offset relative to the shaft 118. The invention is however not limited to this type of cam, and those skilled in the art may consider other shapes than a cylinder of revolution.

[0173] The cam 118 cooperates with at least one through opening 115c formed in the side wall of the hollow cylindrical body 115 in order to impose one or the other of the engaged position and the disengaged position on the piezoelectric finger. In particular, the at least one through opening 115c formed in the side wall of the hollow cylindrical body 115 and delimited by an interior surface on which the cam 118 is capable of exerting a force to impose one or the other of the engaged position and the disengaged position on the piezoelectric finger. In particular, the through opening 115c has a shape adapted to allow the passage from one or the other of the engaged position and the disengaged position to the other of these two positions. For example, the through opening may have an elongated shape along a directrix of the hollow cylindrical body.

[0174] It is understood that the cam and the shaft extend along an axis perpendicular to the elongation axis of the piezoelectric finger.

[0175] It is also understood that the shaft can be driven in rotation by means of a motor.

[0176] According to a particularly advantageous embodiment, the piezoelectric vibration means comprise a suspension mechanism configured so that the piezoelectric finger, as soon as it is in its engaged position, imposes a predetermined contact force on the rear face. In other words, the suspension mechanism is configured to allow retraction of the piezoelectric finger, in the hollow cylindrical body, as soon as it comes into contact with the rear face and so as to limit the force exerted by said finger on the rear face to the predetermined contact force.

[0177] According to a particularly advantageous embodiment, the suspension mechanism comprises a spring 119 mounted in compression and bearing on the one hand against the hollow cylindrical body and on the other hand against a shoulder 11c of the piezoelectric foot. The shoulder may in particular be formed by an edge of a jacket in which the piezoelectric finger is fixed. It is accepted in this description that the shoulder is a component of the piezoelectric finger.

[0178] In particular, the suspension mechanism, when no constraint is imposed, holds the piezoelectric finger 111 in abutment, for example by its shoulder, in a direction, called the direct direction, going from the first end towards the second end, against a stop of the hollow cylindrical body. As soon as it comes into contact with the rear face of the analysis cartridge, the piezoelectric finger partially retracts. by exerting a compressive force on the spring 119 in a direction opposite to the forward direction. The choice of an appropriate stiffness constant of the spring 119 makes it possible to impose a predetermined contact force (or bearing force) on the rear face of the analysis cartridge. Alternatively and / or additionally, the piezoelectric piston may comprise means for adjusting the compression of the spring. These adjustment means may in particular comprise a screwing system or a screwing washer cooperating with the hollow cylindrical body. The invention is however not limited to these screwing systems, and those skilled in the art may consider any other technical solution making it possible to adjust the compression of the spring.

[0179] Advantageously, the bearing force can be between 1 N and 50 N, advantageously between 1 N and 25 N, even more advantageously between 1 N and 20 N. Furthermore, the bearing force can be exerted on a surface with an extent of between 4 mm2 and 64 mm2.

[0180] Thus, for a bearing force of 1 N on a surface area of ​​4 mm2 or 64 mm2, the pressure exerted is of the order of 5000 Pa and 156.25 Pa respectively.

[0181] Equivalently, for a bearing force of 50 N on a surface area of ​​4 mm2 or 64 mm2, the pressure exerted is of the order of 125 kPa and 7812.5 Pa, respectively.

[0182] The displacement of the chamber bottom under the effect of the pressing force to start the mixing, and possibly the generation of bubbles, can be between 0.2 and 4 pm, more advantageously between 2 and 4 pm.

[0183] The analysis device 100 may also be configured to move the analysis cartridge 1 and / or the piezoelectric vibration means 110, so as to be able to successively match each of the analysis chambers and the piezoelectric vibration means and thus successively and specifically impose a vibration on the bottom of each of the analysis chambers. Thus, lateral movements of the analysis cartridge may be provided to bring the latter opposite the piezoelectric vibration means. In a complementary manner, the piezoelectric vibration means may be arranged to be moved in a horizontal direction so as to bring the finger of said means into contact with the rear face of the analysis cartridge.

[0184] Thus, and by way of example, the analysis device comprises a worm screw cooperating with the support and configured to impose on said support one or the other of an analysis position and a loading position. The loading position is a position allowing the installation and / or removal of the analysis cartridge from said support, while the analysis position is a position allowing the piezoelectric finger to be engaged against the rear face of the analysis cartridge. Alternatively; it may be considered to implement a rack.

[0185] The analysis device 100 may comprise complementary magnetic means intended to impose a complementary magnetic field in the at least one analysis chamber of the analysis cartridge. The complementary means are advantageously implemented when a non-magnetic layer 6c is considered.

[0186] The analysis device 100 may further comprise means for analyzing the sample present in the at least one analysis chamber 1. These analysis means 120 cooperate with the detection agent 10a. The analysis means 120 may in this respect comprise optical means, and more particularly an epifluorescence microscope.

[0187] More particularly, the analysis means 120 are configured to locate / detect the complexes 12 immobilized on the bottom of the analysis chamber 5 by the magnetic layer 6b. In particular, these immobilized complexes form a pattern imposed by the arrangement of the magnetic regions of the magnetic layer 6b.

[0188] Also, since the detection agents associated with the immobilized complexes 12 carry a marker, it is possible to reveal said immobilized complexes 12.

[0189] In particular, the marker carried by the detection agents may be photoluminescent, for example fluorescent.

[0190] Thus, the analysis means of the analysis device can advantageously comprise a radiation source 121 and a detector 122. The radiation source is in particular intended to induce the emission of a photoluminescence signal by the markers, while the detector is configured to collect said photoluminescence signal.

[0191] The piezoelectric vibration means, as described in the present invention, can be implemented to mix, and / or concentrate, a liquid and / or elements included in this liquid for analysis purposes. These piezoelectric vibration means can also be implemented to move the liquid, for example from one chamber to the other (these two chambers being linked by a fluidic channel), to pump a liquid for example towards a chamber of the analysis cartridge.

Claims

Claims

1. An analysis device (100) for biological analysis to detect the presence and / or concentration of a species in a liquid which comprises: - a support (101) for receiving at least one analysis cartridge (1) so that said analysis cartridge (1) rests on said support (101) by one of its faces, and which comprises an essentially flat rear face, and merged with an XY plane, said analysis cartridge (1) comprising at least one chamber (5) capable of containing a liquid intended to be analyzed; - piezoelectric vibration means (110) provided with a piezoelectric finger (111), said piezoelectric finger (111) extending between two ends called, respectively, first end (111a) and second end (111b), the piezoelectric vibration means (110) being arranged so that the piezoelectric finger (111) can adopt one or the other of two positions called, respectively, engaged position and disengaged position, the engaged position being a position for which the second end (111b) is in abutment against the support (101) or against the rear face when the analysis cartridge (1) rests on the support (101), while the disengaged position is a position for which the second end (111b) is at a distance from the rear face so as to allow the removal of the analysis cartridge (1) and the support (101),the piezoelectric vibration means comprise a hollow cylindrical body (115) which forms with the piezoelectric finger (111) a piston, called a piezoelectric piston, the piezoelectric finger (111) being partially housed, coaxially with said hollow cylindrical body, in the hollow cylindrical body (115) and partly opening out through an opening in said hollow cylindrical body, the piezoelectric vibration means further comprise a guide cylinder (116), in which the hollow cylindrical body (115) is partially housed in sliding connection;, - engagement means configured to allow the passage of the piezoelectric finger (111) between one of the engaged position and the disengaged position to the other of these two positions, the engagement means comprise a cam (117) linked to a shaft (118), the shaft (118) passing through a wall of the guide cylinder (116) and is configured to drive the cam 117 when it is rotated and acting on the hollow cylindrical body (115) to impose a translational movement on it in the direction of elongation of the piezoelectric finger (111), the cam 118 cooperates with at least one through opening (115c) formed in the side wall of the hollow cylindrical body (115) in order to impose one or the other of the engaged position and the disengaged position on the piezoelectric finger, the shaft (118) is advantageously controlled in rotation by means of a motor, in particular a stepping motor.

2. Analysis device (100) according to claim 1, in which the piezoelectric finger (111) is configured to impose a vibration on the rear face as soon as the second end (111b) is pressed against the rear face.

3. Analysis device (100) according to claim 1 or 2, wherein the piezoelectric finger (111) is configured to exert, against the rear face, a bearing force perpendicular to the XY plane when it is in its engaged position.

4. Analysis device (100) according to one of claims 1 to 3, wherein said analysis device (100) comprises complementary magnetic means intended to impose a complementary magnetic field in the at least one chamber (5) of the analysis cartridge (1).

5. Analysis device (100) according to one of claims 1 to 4, wherein said analysis device (100) further comprises means for analyzing the liquid likely to be present in the at least one chamber (5).

6. An analysis device (100) according to claim 5, wherein the analysis means comprise a detector and a radiation source configured to analyze a liquid likely to be present in the analysis chamber (5).

7. Analysis device (100) according to one of claims 1 to 6, in which the support (101) is perforated so as to make the rear face of the analysis cartridge (1) accessible via the second end (111b) when said cartridge rests by its rear face on said support (101).

8. Analysis device (100) according to one of claims 1 to 7, wherein said device comprises loading means cooperating with the support (101) and configured to impose on said support (101) one or the other of an analysis position and a loading position. loading, the loading position being a position allowing the installation and / or removal of the analysis cartridge (1) from said support (101), while the analysis position is a position allowing the piezoelectric finger (111) to be engaged against the rear face of the analysis cartridge (1), advantageously the loading means comprise a worm screw.

9. An analysis device (100) according to claim 8 and claim 5 or 6, wherein the analysis position is also a position allowing analysis of the fluid contained in the chamber (5) by the analysis means.

10. An analysis device (100) according to one of claims 1 to 9, wherein the piezoelectric vibration means comprise a suspension mechanism configured so that the piezoelectric finger (111), when in its engaged position, imposes a predetermined contact force on the rear face.

11. Analysis device (100) according to claim 10, in which the suspension mechanism comprises a spring (119) mounted in compression and bearing on the one hand against the hollow cylindrical body (115) and on the other hand against a shoulder of the piezoelectric foot.

12. An analysis device (100) according to claim 11, wherein the shaft (118) is rotatably mounted about an axis perpendicular to the direction of elongation of the piezoelectric finger (111).

13. Analysis device (100) according to one of claims 1 to 12, in which the support (101) comprises shims configured to force the rear face of the analysis cartridge (1) to coincide with the XY plane.

14. Analysis device (100) according to claim 13, wherein said analysis device (100) comprises additional means for holding the analysis cartridge (1) on the support (101), these additional holding means are in particular configured to hold the analysis cartridge (1) at the vents of said cartridge and communicating with the chamber (5), the additional holding means are also configured to close said vents.

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