DEVICE FOR ANALYSIS OF A LIQUID

Description

DOMAINE DE L'INVENTION

[0001] The technical field of the invention is that of biological analysis for detecting the presence and / or concentration of a species (an analyte) in a liquid, particularly a biological fluid. More specifically, the invention relates to an analytical device configured to cooperate with an analytical cartridge equipped with a chamber containing the liquid to be analyzed. ARRIERE PLAN TECHNOLOGIQUE DE L'INVENTION

[0002] A method for capturing and detecting a species, often referred to as an "analyte," in a liquid, particularly a biological fluid, is known from document EP3447492. The principles of pattern capture and detection implemented by this method are also described in the article by Fratzl et al., "Magnetophoretic induced convective capture of highly diffusive superparamagnetic nanoparticles," Soft Matter, 14. 10.1039 / C7SM02324C.

[0003] This process includes a step in which a sample, consisting of a liquid to be analyzed, is mixed with magnetic particles. These particles are nanometric or, more commonly, sub-micrometric in 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. These elements may include, in particular, a detection antibody or antigen bearing a photoluminescent marker, for example, a fluorescent one.

[0005] At the end of this step, complexes composed of the capture element, the species, and the detection element are formed in the solution. These complexes are then immobilized on a support containing magnetic micro-sources arranged in a specific spatial pattern. The pattern is defined by areas of strong and weak magnetic fields, inducing significant magnetic field gradients. The complexes entrained by the magnetic particles tend to aggregate on the support in the areas where the magnetic field strength is greatest. Photoluminescent (and particularly fluorescent) markers make the specific spatial pattern visible, thus indicating the presence of the analyte in the solution. The average (spatially) intensity of this luminous 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, unbound detection elements bearing photoluminescent markers remain dispersed in suspension in the solution. They contribute to forming a relatively homogeneous background. The average (spatially) intensity of this background constitutes a signal called the "supernatant signal." In addition to the unbound photoluminescent markers, this background also consists of the light intensity emitted by all photoluminescent materials in the sample. Capture elements not bound to the analyte and the detection element are also immobilized on the support, but since they do not bear markers, they do not contribute to the light pattern or background.

[0007] The spatial arrangement of the micro-magnetic field sources within the support plane, along with the light intensity of the patterns revealed by the photoluminescent markers, enables the detection and quantification of the analyte in the sample without washing. This means that the liquid solution is not removed after the complexes have been immobilized on the support surface, which is particularly advantageous. To enable this detection, the sample and the support surface are illuminated to allow the detection of the photoluminescent markers, and a digital image is acquired. This digital image therefore exhibits a spatially variable intensity (within the image plane) 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 allows us to conclude that the analyte is present 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 detection method, the biological fluid is introduced into a cartridge, for example, a single-use cartridge, containing multiple analysis chambers. This cartridge is then inserted into the analytical device. The multiple analysis chambers allow for several analyses to be performed on a single biological fluid sample, with each analysis being conducted independently on samples held in each chamber.

[0010] The cartridge includes a liquid discharge opening, a plurality of vents arranged downstream of the analysis chambers, and a network of channels to fluidly connect the opening to the analysis chambers. The biological fluid sample discharged into the opening spreads by capillary action through the channel network to fill the chambers.

[0011] The implementation of this cartridge, although undeniably offering many advantages, requires a number of steps that should be minimized.

[0012] Furthermore, this implementation also requires ensuring effective dissolution and mixing of the magnetic particles and / or detection elements. US 9,789,483 B2 discloses another analytical device for biological analysis to detect the presence and / or concentration of a species in a liquid.

[0013] One aim of the present invention is to propose an analysis device enabling the implementation of an efficient mixing of magnetic particles and / or detection elements present in an analysis chamber of an analysis cartridge. BREVE DESCRIPTION DE L'INVENTION

[0014] The objective of the present invention is achieved by an analytical device for biological analysis aimed at detecting the presence and / or concentration of a species in a liquid, which comprises: a support for receiving at least one analysis cartridge such that said analysis cartridge rests on said support by one of its faces, and which includes a rear face that is essentially flat and coincides with an XY plane, said analysis cartridge including at least one chamber capable of containing a liquid intended to be analyzed; piezoelectric vibration means provided with a piezoelectric finger, which extends between two ends called, respectively, first end and second end, a hollow cylindrical body which forms with the piezoelectric finger a piston, called the piezoelectric piston, the piezoelectric finger being partially housed, coaxially with said hollow cylindrical body, within the hollow cylindrical body and partially opening through an opening in said hollow cylindrical body, the piezoelectric vibration means further include a guide cylinder,in which the hollow cylindrical body is partially housed by a sliding connection, the piezoelectric vibration means being arranged so that the piezoelectric piston can adopt one of two positions, respectively called the engaged position and the disengaged position, the engaged position being a position in which the second end is in contact with the support or the rear face when the analysis cartridge rests on the support, while the disengaged position is a position in which the second end is away from the support and the rear face so as to allow the removal of the analysis cartridge; engagement means configured to allow the passage of the piezoelectric finger between one of the engaged and disengaged positions and the other of these two positions, the engagement means comprising a cam carried by one end of a shaft,said shaft being in pivot joint with the guide cylinder and passing through the hollow cylindrical body perpendicularly to the piezoelectric finger, the cam, cooperating with a through opening formed in the lateral wall of the hollow cylindrical body so that the piezoelectric piston adopts either the engaged or disengaged position by the sole action of the cam, the shaft is advantageously controlled in rotation by means of a motor, in particular a stepper motor.

[0015] According to one embodiment, the cam is capable of adopting two angular positions around an axis coinciding with the shaft, respectively called the angular engagement position and the angular disengagement position, the angular engagement position being a position for which the cam imposes the piezoelectric piston the engagement position and the angular disengagement position being a position for which the cam imposes the piezoelectric piston the disengagement position.

[0016] According to one embodiment, the through opening is delimited by an inner surface on which the cam is capable of exerting a force to impose one or the other of the engaged position and the disengaged position on the piezoelectric piston, advantageously presents an elongated shape along a director of the hollow cylindrical body.

[0017] According to one implementation method, the piezoelectric finger is configured to impose a vibration on the rear face as soon as the second end is in contact with the rear face.

[0018] According to one embodiment, the piezoelectric finger is configured to exert, against the rear face, a support force perpendicular to the XY plane when it is in its engaged position.

[0019] According to one implementation method, said analysis device includes complementary magnetic means intended to impose a complementary magnetic field in at least one chamber of the analysis cartridge.

[0020] According to one implementation method, said analysis device further includes means for analyzing the liquid likely to be present in at least one chamber.

[0021] According to one implementation method, the analysis means include a detector and a radiation source configured to analyze a liquid that may be present in the analysis chamber.

[0022] According to one embodiment, the support is perforated so as to make the rear face of the analysis cartridge accessible from the second end when said cartridge rests with its rear face on said support.

[0023] According to one embodiment, said device includes loading means cooperating with the support and configured to impose said support into one of an analysis position and a loading position, the loading position being a position allowing the placement 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 include a worm screw.

[0024] According to one implementation method, the analysis position is also a position enabling the analysis of the fluid contained in the chamber by the analytical means.

[0025] According to one embodiment, the piezoelectric vibration means include a suspension mechanism configured so that the piezoelectric finger, once in its engaged position, imposes a predetermined contact force on the rear face.

[0026] According to one embodiment, the suspension mechanism includes a spring mounted in compression and supported on one side against the hollow cylindrical body and on the other side against a shoulder of the piezoelectric foot.

[0027] According to one implementation method, the support includes shims configured to force the rear face of the analysis cartridge to coincide with the XY plane.

[0028] According to one implementation method, the analysis device includes additional means for retaining the analysis cartridge on the support; these additional means are configured in particular to retain the analysis cartridge at the level of vents of said cartridge and communicating with the chamber; the additional means are also configured to close said vents. Brève description des dessins

[0029] Other features and advantages will become apparent in the following description of an analysis cartridge and an analysis device according to the invention, given by way of non-limiting examples, with reference to the accompanying drawings in which: [ Fig.1 ] There [ Fig.1 ] is a schematic, perspective representation of an analysis cartridge that can be implemented according to the principles of the present invention; [ Fig.2 ] There [ Fig.2 ] is a schematic representation of the fluidic section along a cutting plane of said fluidic section parallel to the upper face, the [ Fig.2 ] represents in particular at least one analysis chamber in fluidic communication on the one hand with the opening via the channels and on the other hand with at least one vent via at least one vent channel; [ Fig.3 ] There [ Fig.3 ] is a schematic representation of the cartouche shown in the [ Fig.1 ] in perspective and exploded view; [ Fig.4a ] There [ Fig.4a ] is a schematic representation along a transverse section plane (perpendicular to the main faces) of the cartouche of the [ Fig.1 ] at the level of at least one analysis chamber; [ Fig.4b ] There [ Fig.4b ] is another schematic representation along a transverse section plane (perpendicular to the main faces) of the cartouche of the [ Fig.1 ] at the level of at least one analysis chamber, said cartridge implementing a non-magnetic layer; [ Fig.4c ] There [ Fig.4c ] is a perspective representation of an interleaving film that could be used for assembling the cartridge of the [ Fig.1 ] ; ] Fig.4d ] There [ Fig.4d ] is a schematic top-view representation of a detection pattern defined by the magnetization produced by a magnetic layer integrated into the cartridge holder, the magnetic field present in an analysis chamber, and the magnitude of that field; Fig.5 ] There [ Fig.5 ] is a schematic representation of an analysis chamber filled with a liquid containing the analysis in suspension, magnetic nanoparticles onto which capture agents, detection agents, and the [ Fig.5 ] illustrates in particular the mechanism of complex formation; [ Fig.6 ] There [ Fig.6 ] is a representation of an analysis device implemented according to the principles of the present invention; [ Fig.7a ] ] Fig.7b ] THE figures 7a et 7b are representations of the interior of the analysis device of the [ Fig.6 ], with the finger of the piezoelectric vibration means in a disengaged position, the [ Fig.7b ] being a cross-sectional view; [ Fig.7c ] There [ Fig.7c ] is a representation of the interior of the analysis device of the [ Fig.6 ], the finger of the piezoelectric vibration means being in an engaged position; [ Fig.8 ] There [ Fig.8 ] illustrates, in perspective view, a support that can be implemented within the framework of the present invention; in particular, the support shown in this figure can accommodate two analysis cartridges; [ Fig.9 ] There [ Fig.9 ] is an illustration of the support of the [ Fig.8 ] and accommodating an analysis cartridge on one of its sites; ] Fig.10 ] There [ Fig.10 ] is an illustration of a piezoelectric finger that can be implemented within the framework of the present invention; [ Fig.11 ] There [ Fig.11 ] is a representation, according to a cross-sectional plane along the elongation axis of the piezoelectric finger, of piezoelectric vibration means according to an advantageous embodiment of the present invention; [ Fig.12 ] There [ Fig.12 ] is a representation, from a perspective view, of a hollow cylindrical body used in the piezoelectric vibration means of the [ Fig.11 ] ; ] Fig.13 ] There [ Fig.13 ] is a representation, in perspective view, of a guide cylinder used in the piezoelectric vibration means of the [ Fig.11 ]. DESCRIPTION DETAILLEE DE L'INVENTION

[0030] There [ Fig.1 ] 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.

[0031] The analysis cartridge 1 is, in this respect, suitable for receiving a sample of a liquid, for example a biological liquid, in order to detect the presence of a given analyte in said liquid.

[0032] 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 description of the present invention will nevertheless be limited to the description of a chamber having a single housing and designated by the word "chamber".

[0033] The analysis cartridge 1 may include a gripping end 1a for handling it. The gripping end 1a may bear a label, for example with a barcode or a two-dimensional code, enabling identification and traceability of analyses performed using the analysis cartridge 1 in question. Alternatively, the identification means may include an RFID chip.

[0034] The analysis cartridge 1 also includes an active section 1b formed, for example, in the extension of the gripping end 1a.

[0035] The active section 1b is generally planar in shape and comprises two main faces called, respectively, the upper face and the lower face.

[0036] The analysis cartridge 1 may include at least one pouring opening 2 which allows the introduction of a liquid into the analysis cartridge 1. This opening 2 leads in particular to the upper face of the active section 1b.

[0037] The opening 2 is in particular in fluidic communication with at least one analysis chamber 5. In particular, the active section includes at least one microfluidic channel 4 ensuring fluidic communication between the opening 2 and at least one analysis chamber 5. In other words, at least one microfluidic channel 4 ensures the flow and distribution of the liquid poured into the opening 2 towards at least one analysis chamber.

[0038] The analysis cartridge 1 may also include at least one vent 3 in fluidic communication with at least one analysis chamber 5 ( figures 1 et 2 ). At least one vent 3 is specifically configured to allow the evacuation of air that may be present in at least one analysis chamber 5 during its filling with liquid. In particular, fluid communication between at least one analysis chamber 5 and at least one vent 3 is ensured by at least one vent channel 4'.

[0039] Thus, in operation, a sample of liquid is introduced, for example by means of a pipette, into the opening 2. The sample then flows into at least one analysis chamber 5 via at least one microfluidic channel 4. The air likely to be present in at least one analysis chamber 5 is expelled during the flow of the liquid in said analysis chamber 5 towards at least one vent 3.

[0040] In the case of multiple 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. "Sequential flow" refers to the filling of the analysis chambers 5 in a predetermined order. Specifically, according to this principle, the flow in a given chamber only begins when the analysis chamber preceding it in the filling order is completely full.

[0041] In the case of a plurality of analysis chambers 5, it can also be provided that the analysis cartridge includes a plurality of openings, for example an opening dedicated to each chamber of the cartridge.

[0042] The analysis cartridge 1 shown in the [ Fig.1 ] may further include a reservoir 2' above the opening 2 whose volume equals that of the microfluidic network formed by at least one microfluidic channel 4, at least one analysis chamber 5 and at least one vent channel 4'. In this respect, this volume may be between 5 mm 3< and 500 mm 3< , and more precisely between 20 mm 3< and 100 mm 3< .

[0043] Equivalently, at least one vent 3 is surmounted by a peripheral wall 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' to prevent liquid from escaping from the analysis cartridge 1. This arrangement helps to limit health-related problems, or even damage to an analysis device (described later in the statement) into which the analysis cartridge 1 is intended to be inserted.

[0044] By way of illustration, the analysis cartridge 1 may have dimensions between 2 cm and 10 cm in width and length, and a thickness between 4 mm and 10 mm. The at least one analysis chamber 5 may have a volume typically between 1 mm³ and 50 mm³ to receive the sample, advantageously between 5 mm³ and 25 mm³.

[0045] According to a non-limiting example shown in the [ 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.

[0046] At least one analysis chamber 5, at least one microfluidic channel 4 and at least one vent channel 4' form a microfluidic network of the analysis cartridge 1. This microfluidic network is defined in particular 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 together.

[0047] Each channel 4, 4' is delimited, on the one hand, by the main surfaces of the support 6 and the cover 7, forming, respectively, a bottom and an arch, and on the other hand, by side walls connecting the bottom and the arch. The distance separating the bottom and the arch of a channel 4, 4' defines a channel height, while the distance separating two opposing side walls defines a channel width. The arch, the bottom, and the side walls together form the walls of the chamber.

[0048] Equivalently, at least one analysis chamber 5 is also delimited by the main surfaces of the support 6 and the hood 7 forming, respectively, a chamber bottom 5a and a chamber vault 5b ( figures 4a et 4b ). The at least one chamber 5 further comprises side walls of chamber 5c which extend from the bottom of chamber 5a towards the vault of chamber 5b. It is understood, however, that the at least one analysis chamber 5a may be without a vault, and for example form an open well at the level of the active section.

[0049] He also heard that the side walls of at least one chamber may be deformable.

[0050] The upper cover 7, at least for the portion that overhangs at least one analysis chamber 5, may be made of a material transparent to a photoluminescence signal emitted by detection agents described later in the statement. The material forming the upper cover 7 may comprise at least one of the following materials: a plastic material, for example based on polycarbonate, cycloolefin copolymer, or polystyrene; or glass.

[0051] The outer surface of the hood 7 can be optically polished at least directly opposite at least one analysis chamber 5.

[0052] The microfluidic network, such as the one shown on the [ Fig.2 ], therefore, extends in the principal plane of the analysis cartridge 1. It is millimeter-sized, meaning that the width of the channels 4, 4' and the analysis chambers 5 is typically between 0.1 mm and 10 mm. The height of these elements, i.e., the distance from the bottom of an arch, is also between 0.1 mm and 10 mm. The liquid that can be introduced at the opening 2 spreads through the microfluidic network by capillary action.

[0053] The analysis cartridge 1 according to the present invention may also include at least a first cluster 9 adhering to the bottom of at least one analysis chamber 5 ( [ Fig.4a ]). The at least first cluster 9 is notably formed of magnetic nanoparticles 9a held together, and onto which capture agents 9b are grafted ([ Fig.5 ]).

[0054] Alternatively, it may be considered to place at least one first cluster on the vault 5b of 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 later in the statement.

[0055] A first cluster can advantageously have a volume between 0.1 µl and 5 µl and advantageously between 0.5 µl and 2 µl.

[0056] By "held together," we mean a group of nanoparticles bonded together. This cohesion between the nanoparticles can be direct or indirect. Direct cohesion can be achieved, for example, by dry or freeze-dried nanoparticles, while indirect cohesion can be achieved by an encapsulating material. In this regard, the encapsulating material can include sugars (trehalose, glucose, etc.), viscous solutions (for example, Tween), or glycerol.

[0057] Keeping the nanoparticles together, and in the form of clusters, ensures better stability of the latter over time.

[0058] The implementation of an encapsulation material makes it easier to suspend nanoparticles as presented later in the description.

[0059] Magnetic nanoparticles (9a) can be nanometric in size, typically between 25 nm and 500 nm, and preferably between 100 and 300 nm. They are generally spherical in shape. These nanoparticles exhibit superparamagnetic properties and are biocompatible. They can also be coated with a polymer (such as polystyrene) with a surface treatment that allows them to be functionalized, for example, with Ac or Ag proteins. 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.

[0060] Capture agents 9b are capable of binding specifically to the analyte likely to be present in the fluid. In this respect, the analyte can be an antigen, while the capture agent 9b comprises an antibody (the reverse configuration is also possible).

[0061] The analysis cartridge 1 may also include at least a second cluster 10 adhering to the bottom of at least one analysis chamber 5 ( figures 4a et 4b ). At least a second cluster 10 is notably formed of interconnected detection agents 10a([ Fig.5 ]).

[0062] It is understood, without needing to be explicitly stated, that the first cluster 9 and the second cluster 10 can form a single cluster. Furthermore, the first cluster 9 and the second cluster 10 can either be deposited on a wall of the chamber.

[0063] Advantageously, the first cluster 9 and / or the second cluster 10 are based on a surface energy density associated with a hydrophobic surface. The surface energy density can be determined, as is well known, by measuring the contact angle of a water droplet placed on the surface whose energy is to be measured. 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 allows us to impose a relatively spherical shape on one or both of the first and second clusters.

[0064] A second cluster may advantageously have a volume between 0.1 µl and 5 µl and advantageously between 0.5 µl and 2 µl.

[0065] At least one first cluster 9 and at least one second cluster 10 are both intended to enable, respectively, the capture, or even immobilization, of an analyte 11 present in a liquid, and the detection, or even quantification, of 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 ]).

[0066] Magnetic nanoparticles are used to isolate the complexes, while detection agents enable their detection.

[0067] 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 at least one analysis chamber via the opening 2.

[0068] The formation of 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.

[0069] This suspension process may include separating the first and second clusters from the bottom of chamber 5a, as well as separating the elements from each other to disperse them within the sample. To this end, piezoelectric vibration methods 110, described later in this document, may be used.

[0070] These piezoelectric vibration devices 110 are particularly suitable for imposing a vibration on the bottom of chamber 5a. 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.

[0071] 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. Also 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 within + / - 15%, advantageously within + / - 10%, and even more advantageously within + / - 5% of the resonance frequency of the analysis chamber). Advantageously, the resonance frequency of the analysis chamber 5 is on the order of 50 kHz, or on the order of 80 kHz, or on the order of 110 kHz.

[0072] An analysis chamber exhibiting such resonance frequencies may comprise, along a cross-sectional plane perpendicular to the rear face of the cartridge, a rectangular section terminating at each end in an opening whose cross-section, along the same plane, is triangular. The length and width of the rectangular section are 8.4 mm and 2.4 mm, respectively, while the base and height of the triangular section are 2.4 mm and 4 mm, respectively. The height of the analysis chamber is 390 µm.

[0073] According to a second variant, the vibration can be imposed in the form of cycles, for example, repeated cycles. In this respect, a cycle can include a sweep in increasing or decreasing frequency, and more specifically, a frequency sweep around the resonant frequency of the analysis chamber. The complete frequency sweep can last from 10 seconds to 200 seconds. In particular, this frequency sweep includes an increment or decrement of the frequency in steps.

[0074] In particular, each step corresponds to maintaining the frequency for a duration that can be between 2 seconds and 10 seconds in order to allow the liquid to move sufficiently for a minimal mixing effect.

[0075] For example, a cycle might involve a frequency sweep from 110 kHz to 120 kHz, or conversely, a frequency sweep from 120 kHz to 110 kHz. This sweep can be executed in 1 kHz steps, with the vibration sustained for a few seconds, specifically 2 seconds, at each step.

[0076] As another example, the vibrational sequence may include the repetition of an elementary sequence which includes a first cycle and a second cycle.

[0077] The first cycle may include a frequency sweep from 120 kHz to 111 kHz in 1 kHz steps and a holding of the vibration at each step for 2 seconds.

[0078] The second cycle may include a frequency sweep from 110 kHz to 119 kHz in 1 kHz steps and a holding of the vibration at each step for 2 seconds.

[0079] This basic sequence can, for example, be repeated from 1 to 4 times.

[0080] 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) either continuously or as 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 resonant frequency and its harmonics).

[0081] A particularly advantageous feature is that the 5c side walls can be structured to create vortices that promote mixing within the sample as it flows through the analysis chamber. This structuring of the 5c side walls can include a crenellated surface.

[0082] In a particularly advantageous manner, gas, and more particularly air, is initially trapped in the side wall 5c of at least one chamber 5.

[0083] The trapped gas can be released under the action of a mechanical stress applied to at least one analysis chamber and thus generate gas bubbles on the side wall of at least one chamber as soon as the liquid sample is present in at least one chamber 5. This mechanical stress can, in particular, be applied to the rear face of the analysis cartridge 1.

[0084] According to an advantageous embodiment, the side walls 5c of at least one chamber 5 can be made of a porous material. The gas is initially located in the pores of the porous material.

[0085] According to an alternative or complementary embodiment, the gas can initially be trapped in slots 5e opening onto the side walls ([ Fig.4c ]).

[0086] The 5e slits can have a length between 100 µm and 1000 µm, and a cross-section whose largest dimension is between 100 µm and 400 µm.

[0087] The cross-section of a slit can include at least one of the following shapes: square, rectangle, circle.

[0088] According to the present invention, once the gas bubbles are generated (in particular under the effect of the previously described stress), the acoustic pressure field, generated by vibration of the bottom of the chamber, makes it possible to make them vibrate in the liquid present in the analysis chamber.

[0089] These vibrating gas bubbles then act as additional vibrating agents which help to improve the mixing of the liquid present in the analysis chamber.

[0090] This effect can nevertheless be optimized by forcing the gas bubbles to vibrate at a frequency close to their resonant frequency (by "close to the resonant frequency," we mean a frequency within + / - 15%, advantageously within + / - 10%, and even more advantageously within + / - 5% of the gas bubbles' resonant frequency). Indeed, under these conditions, the contribution of the gas bubbles to the mixture is amplified, especially since some bubbles are capable of transferring energy through their implosion and the resulting shock wave.

[0091] To this end, the pores and / or slits trapping the gas can be configured so that the gas bubbles that may be generated have a resonance frequency close to that of the analysis chamber.

[0092] Specifically, for the specified slit sizes, bubble sizes can range from 50 µm to 500 µm. For this range of bubble sizes, resonance frequencies range from 20 kHz to 500 kHz.

[0093] According to the present invention, the analysis cartridge 1 may include a magnetic layer 6b ([ Fig.4a arranged to immobilize the magnetic nanoparticles 9a of at least one analysis chamber 5 on the bottom of said chamber. It is therefore understood that this magnetic layer also immobilizes the complexes 12. The magnetic layer 6b is advantageously microstructured so that the magnetic nanoparticles immobilized on the bottom of the analysis chamber 5 form a predefined pattern.

[0094] The magnetic layer 6b may in this respect comprise a repeated juxtaposition of at least a first region 6b1 and a second region 6b2. More particularly, the first region 6b1 may exhibit magnetic polarization along a first direction, and the second region 6b2 may exhibit either zero magnetic polarization or magnetic polarization along a second direction different, preferably at 180°, from the first direction ([ Fig.4a ]).

[0095] The support 6 can in particular be arranged so that it comprises, from its main face to its 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 ( figures 3 , 4a et 4b ).

[0096] The rigid substrate 6a may comprise a plastic material. The magnetic layer 6b may be disposed on the substrate 6a, or integrated into this substrate, at least at the level of the analysis chambers 5 of the microfluidic network.

[0097] The 6b magnetic layer can comprise magnetic composite materials, such as ferrites, randomly distributed within a polymer or oriented along a pre-orientation axis. This 6b magnetic layer can be similar to a conventional magnetic recording tape. In this latter case, the microstructuring of a magnetic layer is associated with magnetic coding (notably via a magnetic recording / reading head). More specifically, microstructuring in this case involves creating magnetic zones that can exhibit different magnetizations from one zone to another in terms of orientation and / or amplitude. For example, two adjacent zones can have two opposite orientations, specifically 180° apart.

[0098] The substrate 6a may also include a non-magnetic layer 6c (or a plurality of such films) intercalated between the magnetic layer 6b and the intercalating film 6d. This optional non-magnetic layer 6c is intended to move the magnetic layer 6b away from the bottom of the analysis chamber 5.

[0099] By "non-magnetic layer" we mean a layer whose magnetic susceptibility is zero or even less (in absolute value) than 10 -3.

[0100] The non-magnetic layer 6c can, for example, comprise a plastic material, such as polypropylene on acrylic.

[0101] In the example shown above, the 6d interlayer film defines the microfluidic network. In particular, the 6d interlayer film illustrated in the [ Fig.4c ] features a cut-out 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 cut-out pattern of the film 6d. These recesses, possibly in combination with additional recesses formed in the upper cover 7, constitute the microfluidic network of the cartridge 1.

[0102] Advantageously, the interlayer film 6d is an adhesive film, which also allows the upper cover 7 to be hermetically sealed to the support 6 at their contact surfaces, i.e., around the recesses. It can, for example, be a double-sided adhesive film, thus simultaneously bonding it to the substrate 6a and to the upper cover 7. As is well known, such an interlayer film 6d can be made of a strip, for example plastic, with both sides coated with an adhesive material.

[0103] Advantageously, gas or air bubbles, when mechanical stress is applied to the bottom of the chamber, can be generated by the release of gas trapped in the interlayer film. This film can therefore be porous and / or contain slits, for example, formed during the cutting of the pattern corresponding to the microfluidic network.

[0104] 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 on the figures 4a et 4b ). As shown on the [ Fig.4d ] which represents the magnetic layer 6b in top view, the magnetically polarized regions extend in a line along a principal direction P in the example shown.

[0105] Regions of relatively strong magnetic intensity, known as attraction zones, are observed at the interfaces between areas of different polarization. Attraction zones are arranged in the form of a plurality of lines Za oriented along the principal direction P. The specific arrangement of these lines, in combination, defines a detection pattern.

[0106] It is understood that the online arrangement given as an example is only one particular case of a detection pattern. An analysis cartridge 1 is more generally equipped with magnetically polarized regions defining a well-defined detection pattern, but whose configuration can be freely chosen.

[0107] The Bc field generated by the magnetic layer 6b and its magnitude are also shown on the [ Fig.4d As will be explained later in this discussion, it can be useful to add an additional (or complementary) external field, Bext, to the field produced by layer 6b. This is shown on the [ Fig.4d This external magnetic field Bext combines with the magnetic field Bc produced by the layer, and the magnitude of this combined field is also considered. It is observed that applying this external magnetic field Bext can eliminate certain areas of attraction Za produced when only the field provided by the magnetic layer 6b is present. However, in all cases, these areas of attraction are arranged along lines Za oriented along the principal direction P, or more generally, according to a detection pattern whose characteristics are precisely defined.

[0108] In the case of an analysis chamber 5 having the dimensions indicated above, it is possible to consider forming a detection pattern comprising between 2 and 50 lines, these having a thickness between 1 µm and 150 µm (advantageously between 5 µm and 30 µm) and separated from each other by a spacing between 5 µm and 300 µm, advantageously between 25 µm and 150 µm.

[0109] Based on this description, the inventors calculated the surface gradient on the surface of a non-magnetic layer with a thickness close to 55 µm and resting on a magnetic layer.

[0110] The micro-magnets in the magnetic layer, upon which the non-magnetic layer rests, are 50 µm wide and 10 µm high. These micro-magnets are plane-polarized and alternate with each other. In this calculation, a magnetic field source made of NdFeB with a remanence of 1.2 T is also used below this magnetic layer. This source imposes a magnetic field with an amplitude between 0.005 Tesla and 0.3 Tesla.

[0111] In this calculation, the inventors were able to demonstrate that the gradients on the surface of the non-magnetic layer range from 50 T / m to 150 T / m, and can be extended to within approximately an order of magnitude. These gradients result in a magnetic force exerted on the particles. This force is capable of retaining the magnetic particles (particularly clusters) and also contributes to their immobilization (described at the end of this application).

[0112] Thus, when a liquid sample is introduced into the analysis cartridge 1, it flows through the microfluidic channels 4 to fill at least one analysis chamber 5 and propagates through the vent channels 4'. Vibration and mechanical stress are applied to 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 applied to the bottom suspends, and if necessary mixes, the elements forming the first and second clusters. This acoustic pressure field can also cause the gas bubbles to vibrate.

[0113] The vibration of these elements also contributes, to some extent, to the suspension and mixing of 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 subsequent 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 preferentially agglomerating at the maxima of the magnetic field intensity norm (induced by the micro-sources and possibly the external magnetic field), and thus arranging themselves according to the detection pattern defined by the magnetic layer 6b. Excess detection elements remain suspended in the sample.

[0114] It can be foreseen that each analysis chamber 5 of a cartridge 1 is prepared to receive capture elements and detection elements of different kinds, so as to carry out multiple analyses of a liquid sample introduced into the analysis cartridge 1. It can also be foreseen that the detection pattern encoded by the portion of the magnetic layer 6b which is disposed at the level of a chamber 5 is different from one chamber to another.

[0115] It is also possible to consider a magnetic layer which includes an area devoid of magnetic areas, and directly above which the first cluster is formed (the re-suspension of the magnetic nanoparticles of the first cluster can thus be facilitated).

[0116] 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.

[0117] The invention also relates to an analysis device 100 intended to cooperate with the analysis cartridge ([ Fig.6 ]).

[0118] The analysis device 100 includes in particular a support 101 intended to receive at least one analysis cartridge 1 for the purpose of analyzing the liquid sample contained in at least one analysis chamber 5 ( figures 7a à 7c More specifically, the support 101 is designed to receive the analysis cartridge 1 such that said analysis cartridge 1 rests on said support 101 by one of its faces. In the remainder of this statement, it will be considered that the analysis cartridge rests by its rear face. However, this latter aspect is not such as to limit the present invention, and a person skilled in the art may consider an analysis cartridge to rest by one of its faces opposite the rear face.

[0119] There [ Fig.8 Figure 101 illustrates in this regard a support that can be implemented within the framework of the present invention. In particular, the support 101 shown in this figure can accommodate two analysis cartridges.

[0120] The support 101 can also be configured to allow the insertion of an analysis cartridge 1 by means of a sliding movement in the direction "A" ( Fig.8 ]).

[0121] In particular, the support 101 includes a base, referred to as the base support 101a, and side walls 101b and 101c configured to guide the insertion of an analysis cartridge 1.

[0122] Snap-on means 102 can also be arranged on the support base 101a. Said snap-on 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.

[0123] The support 101 is also openwork and includes a window 103 formed on the base of the support 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 positioned directly above the analysis chamber 5 of the analysis cartridge 1 placed on the support 101.

[0124] The support can alternatively be configured to guide the vibrations imposed by the piezoelectric finger. In this respect, the support may include 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 at least one analysis chamber, and more specifically at the level of each analysis chamber when there are multiple analysis chambers.

[0125] When placed on the support 101, the rear face of the analysis cartridge 1 coincides (i.e., is coplanar) with the XY plane. In particular, this XY plane is parallel to the base of the support 101a. The XY plane can, for example, be horizontal.

[0126] The side walls 101b and 101c also include cleats 104 which extend from a free edge of each of the side walls 101b and 101c ([ Fig.9 ] ).

[0127] The cleats 104 (or wedges), along with the locking means 102, ensure that the analysis cartridge 1 is held securely on the support 101 and that the rear face of said cartridge 1 is coplanar with the XY plane. These retention means, as described, are configured to ensure coplanarity between the XY plane and the rear face of the analysis cartridge. However, the invention is not limited to the means described herein, and a person skilled in the art may implement any means ensuring coplanarity between the XY plane and the rear face of the analysis cartridge.

[0128] Spring means can be arranged on the support base 101a. These spring means are specifically configured to press the analysis cartridge 1 against the tabs 104, thus ensuring coplanarity between the XY plane and the rear face of the analysis cartridge. The spring means may include levers. However, this latter aspect does not limit the scope of the present invention, and a person skilled in the art may implement any other type of means exhibiting such functionality.

[0129] The 100 analysis device may also include additional means for securing the analysis cartridge to the support. These additional means are specifically configured to hold the analysis cartridge at its vents, and in particular to seal these vents. Sealing the vents prevents a pumping effect of the liquid residing in the chamber and consequently allows for higher vibration amplitudes imposed by the piezoelectric finger. This latter aspect thus enables shorter mixing times.

[0130] The analysis device 100 also includes a stop rail. This stop rail is specifically arranged to be positioned opposite a face of the analysis cartridge on the rear face. In particular, the stop rail is designed to limit the movement of the analysis cartridge when the piezoelectric finger is pressed against the rear face. The support may also include one or more notches formed on its lateral walls 101a and 101b, allowing contact (known as a stop contact) between the stop rail and the analysis cartridge.

[0131] The analysis device 100 also includes piezoelectric vibration means 110 arranged to impose a vibration on the bottom of the analysis chamber so as to generate an acoustic pressure field in a liquid likely to be present in at least one analysis chamber 5.

[0132] The piezoelectric vibration means 110 may include a transducer, in particular an elliptical transducer of the Elliptec ™ type.

[0133] Alternatively, the piezoelectric vibration means 110 may include a piezoelectric stack (Piezostack). The piezoelectric vibration means 110 may include a Langevin transducer (a Langevin transducer is made by a stack of ceramics held between two metal parts that ensure a clamping of the assembly).

[0134] In this respect, the inventors were able to demonstrate that these linear transducers exhibited good mixing dynamics.

[0135] Bolt-clamped Langevin ultrasonic transducers are also very effective.

[0136] Advantageously, the piezoelectric vibration means 110 comprise a piezoelectric finger 111 extending between a first end 111a and a second end 111b. It is understood, without further specification, that a "finger," insofar as it extends between a first and a second end, is an element of generally elongated shape. Typically, the piezoelectric finger may be cylindrical. 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 a point, a flat surface, rounded, or comprise a plurality of contact points (rake-shaped).

[0137] As illustrated in the [ Fig.10 The piezoelectric finger 111 may include a piezoelectric stack 112 interposed between a first element 113 and a second element 114, both generally cylindrical in shape. The first element 112 extends, in particular, from the first end 111a to the piezoelectric stack 112, while the second element extends from the piezoelectric stack 112 to the second end 111b. It is understood that the first element, the piezoelectric stack, and the second element are mechanically connected to one another in such a way as to ensure a preload between these different elements. The preload may be at least 10 times greater than the bearing force exerted by the second end when the latter is in contact with the rear face or the support.Specifically, this prestress improves the coupling between the piezoelectric stack and elements 113 and 114, thereby limiting the influence of the support force on the vibration modes of the stack 112. In other words, the prestress can exceed 20 MPa, advantageously exceed 35 MPa, and even more advantageously exceed 50 MPa. The prestress improves the transmission efficiency of vibrations generated by the piezoelectric finger to the analysis cartridge.

[0138] The piezoelectric vibration means 110 are arranged so that the piezoelectric finger 111 can adopt one of two positions called, respectively, engaged position and disengaged position.

[0139] Specifically, the engaged position is a position in which the second end is pressed against the rear face when the analysis cartridge rests on the support, while the disengaged position is a position in which the contact end is away from the rear face so as to allow removal of the analysis cartridge 1.

[0140] The transition from one of these two positions to the other may involve a pivoting or translational movement.

[0141] Advantageously, the support force exerted by the piezoelectric finger on the rear face is perpendicular to the YZ plane when said finger is in its engaged position.

[0142] The analysis device 100 may also include engagement means configured to permit the passage of the piezoelectric finger between one of the engaged and disengaged positions to the other of these two positions.

[0143] As an example, and as illustrated in the [ Fig.7a ], to the [ Fig.7b ] and to the [ Fig.7c ], the piezoelectric vibration means 110 may include a lever 110a on which the piezoelectric finger is mounted. More particularly, the lever 110a is rotatably mounted about an axis fixed to the analysis device 100. In particular, at the [ Fig.7a ] and to the [ Fig.7b ], the lever 110a forces the piezoelectric finger 111 into its disengaged position. In other words, the second end 111b of the piezoelectric finger 111 is at a distance from the rear face of the analysis cartridge resting on the support 101. At the [ Fig.7c ], the piezoelectric finger 111 is in its engaged position and therefore presents its second end 111b in contact with the rear face of the analysis cartridge 1. According to this aspect, the engagement means may include a motor.

[0144] There [ Fig.11 ] illustrates an example of piezoelectric vibration means for which the passage from one of the engaged and disengaged positions to the other of these two positions implies a translational movement.

[0145] This example specifically involves the movement of the piezoelectric finger along a direction parallel to its extension direction. More precisely, this translational movement can be perpendicular to the XY plane. It is therefore understood, without further ado, that the piezoelectric finger can be mounted perpendicular to the XY plane.

[0146] According to the invention, as illustrated in the [ Fig.11 ] and to the [ Fig.12 The piezoelectric vibration means comprise a hollow cylindrical body 115 which, together with the piezoelectric finger 111, forms a piston, called the piezoelectric piston. In particular, the piezoelectric finger 111 is partially housed coaxially within the hollow cylindrical body 115. In other words, a section of the piezoelectric finger opens through an opening 115a in the hollow cylindrical body 115. It is understood that the section of the piezoelectric finger opening through the opening includes the second end 111b. The hollow cylindrical body 115 includes a lateral wall 115b giving it its cylindrical shape.

[0147] The piezoelectric vibration means further include a guide cylinder 116 ([ Fig.11 ] And [ Fig.13 ]), in which the hollow cylindrical body is partially housed in a sliding joint ([ Fig.11 ]). In particular, the hollow cylindrical body 115 is mounted in the guide cylinder 116 so that the elongation axis of the piezoelectric finger coincides with an axis of revolution of the guide cylinder 116.

[0148] 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.

[0149] The transition from the engaged to the disengaged position is, according to the present invention, controlled by the engagement means. In particular, and as illustrated in [ Fig.11These engagement means comprise a cam 117 fixedly connected to a shaft 118. In particular, the shaft 118 is rotatably mounted about a fixed axis of the analysis device 100. More specifically, the shaft 118 passes through a wall of the guide cylinder 116 (the shaft is, in particular, connected to the guide cylinder via a pivot joint) and is configured to drive the cam 117 when rotated. In particular, the cam 117 may comprise a cylindrical block offset from the shaft 118. In examples not forming part of the invention, those skilled in the art may consider shapes other than a cylinder of revolution.

[0150] The cam 117 cooperates with at least one through-hole 115c formed in the lateral wall of the hollow cylindrical body 115 in order to force, by the sole action of the cam 117, one of the engaged and disengaged positions of the piezoelectric finger. Specifically, the at least one through-hole 115c formed in the lateral wall of the hollow cylindrical body 115 and delimited by an inner surface on which the cam 117 can exert a force to force one of the engaged and disengaged positions of the piezoelectric finger. In particular, the through-hole 115c has a shape adapted to allow passage from one of the engaged and disengaged positions to the other of these two positions. For example, the through-hole may have an elongated shape along a direction of the hollow cylindrical body.

[0151] Thus, in operation, the cam is likely to adopt two angular positions around an axis coinciding with the shaft, called respectively the angular position of engagement and the angular position of disengagement, the angular position of engagement being a position for which the cam imposes the position of engagement on the piezoelectric piston and the angular position of disengagement being a position for which the cam imposes the position of disengagement on the piezoelectric piston.

[0152] The arrangement of the means of engagement as described above makes them more compact than the systems known to the person skilled in the art.

[0153] It is understood that the cam and the shaft extend along an axis perpendicular to the elongation axis of the piezoelectric finger.

[0154] It is also understood that the shaft can be driven into rotation by means of a motor.

[0155] In a particularly advantageous embodiment, the piezoelectric vibration means include a suspension mechanism configured so that the piezoelectric finger, once in its engaged position, exerts a predetermined contact force on the rear face. In other words, the suspension mechanism is configured to allow the piezoelectric finger to retract into the hollow cylindrical body as soon as it makes contact with the rear face, thus limiting the force exerted by the finger on the rear face to the predetermined contact force.

[0156] In a particularly advantageous embodiment, the suspension mechanism comprises a spring mounted in compression and bearing on one side against the hollow cylindrical body and on the other against a shoulder 111c of the piezoelectric foot. The shoulder may, in particular, be formed by an edge of a sleeve in which the piezoelectric finger is fixed. It is assumed in this description that the shoulder is a component of the piezoelectric finger.

[0157] Specifically, the suspension mechanism, when no constraint is applied, holds the piezoelectric finger 111 against a stop, for example by its shoulder, in a direction, called the forward direction, from the first end to the second end, against a stop on the hollow cylindrical body. As soon as it comes into contact with the rear face of the analysis cartridge, the piezoelectric finger partially retracts, exerting a compressive force on the spring in a direction opposite to the forward direction. Choosing an appropriate spring constant for the spring 119 makes it possible to apply a predetermined contact force (or support force) to the rear face of the analysis cartridge. Alternatively and / or additionally, the piezoelectric piston may include means for adjusting the spring compression. These adjustment means may, in particular, include a screw system or a screw washer cooperating with the hollow cylindrical body.The invention is not limited to these screw systems, however, and a person skilled in the art may consider any other technical solution allowing adjustment of the spring compression.

[0158] Advantageously, the support 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 support force can be exerted on a surface with an area between 4 mm² and 64 mm².

[0159] Thus, for a support force of 1 N on a surface of an extent of 4 mm² or 64 mm², the pressure exerted is on the order of, respectively, 5000 Pa and 156.25 Pa.

[0160] Equivalently, for a support force of 50 N on a surface of an extent of 4 mm² or 64 mm², the pressure exerted is on the order of, respectively, 125 kPa and 7812.5 Pa.

[0161] The displacement of the chamber bottom under the effect of the support force to start the mixing, and possibly the generation of bubbles, can be between 0.2 and 4 µm, more advantageously between 2 and 4 µm.

[0162] The analysis device 100 can also be configured to move the analysis cartridge 1 and / or the piezoelectric vibration means 110, so as to successively align each of the analysis chambers with the piezoelectric vibration means and thus successively and specifically impart a vibration to the bottom of each analysis chamber. Lateral movements of the analysis cartridge can be provided to bring it into contact with the piezoelectric vibration means. Additionally, the piezoelectric vibration means can be arranged to move horizontally so as to bring the tip of said means into contact with the rear face of the analysis cartridge.

[0163] Thus, by way of example, the analysis device includes a worm gear cooperating with the support and configured to force said support into either an analysis position or a loading position. The loading position allows the analysis cartridge to be inserted into and / or removed from said support, while the analysis position allows the piezoelectric finger to be engaged against the rear face of the analysis cartridge. Alternatively, a rack and pinion mechanism could be used.

[0164] The analysis device 100 may include complementary magnetic means for imposing a complementary magnetic field in at least one analysis chamber of the analysis cartridge. These complementary means are advantageously implemented when a non-magnetic layer 6c is considered.

[0165] The analysis device 100 may further include means for analyzing the sample present in at least one analysis chamber 1. These analysis means 120 cooperate with the detection agent 10a. The analysis means 120 may in this respect include optical means, and more particularly an epifluorescence microscope.

[0166] More specifically, 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.

[0167] Also, as soon as the detection agents associated with the immobilized complexes 12 carry a marker, it is possible to reveal said immobilized complexes 12.

[0168] In particular, the marker carried by the detection agents can be photoluminescent, for example fluorescent.

[0169] Thus, the analytical means of the analytical device may advantageously include a radiation source 121 and a detector 122. The radiation source is specifically intended to induce the emission of a photoluminescence signal by the markers, while the detector is configured to collect said photoluminescence signal.

[0170] The piezoelectric vibration means described in the present invention can be used to mix and / or concentrate a liquid and / or elements contained therein for analytical purposes. These piezoelectric vibration means can also be used to move the liquid, for example, from one chamber to another (the two chambers being connected by a fluidic channel), or to pump a liquid, for example, into a chamber of the analytical cartridge.

Claims

1. Analysis device (100) for biological analysis to detect the presence and / or concentration of a specimen in a liquid, comprising: - a support (101) for receiving at least one analysis cartridge (1) such that said analysis cartridge (1) rests on said support (101) via one of its faces, and which comprises a mostly planar rear face, coincident with an XY plane, said analysis cartridge (1) comprising at least one chamber (5) capable of containing a liquid to be analyzed; - piezoelectric vibration means (110) comprising a piezoelectric finger (111) extending between two ends referred to, respectively, as the first end (111a) and the second end (111b), a hollow cylindrical body (115) that forms, together with the piezoelectric finger (111), a piston, referred to as a piezoelectric piston, the piezoelectric finger (111) being partially housed, coaxially with said hollow cylindrical body, within the hollow cylindrical body (115) and partially protruding through an opening in said hollow cylindrical body, the piezoelectric vibration means further comprising a guide cylinder (116), in which the hollow cylindrical body (115) is partially housed in a sliding connection, the piezoelectric vibration means (110) being arranged such that the piezoelectric piston can assume one of two positions, referred to respectively as the engaged position and the disengaged position, the engaged position being a position in which the second end (111b) rests against the support (101) or against the rear face when the test cartridge (1) rests on the support (101), whereas the disengaged position is a position in which the second end (111b) is apart from the rear face so as to allow removal of the analysis cartridge (1) and the support (101); - engagement means configured to allow the piezoelectric finger (111) to move from one of the engaged and disengaged positions to the other of these two positions, the engagement means comprising a cam (117) carried by one end of a shaft (118), said shaft (118) being pivotally connected to the guide cylinder and passing through the hollow cylindrical body perpendicular to the piezoelectric finger, the cam (117), interacting with a through-hole (115c) formed in the side wall of the hollow cylindrical body such that the piezoelectric piston assumes either the engaged position or the disengaged position solely by the action of the cam (117), the shaft (118) is advantageously rotated by a motor, in particular a stepper motor.

2. Analysis device (100) according to claim 1, wherein the cam is capable of assuming two angular positions about an axis coincident with the shaft, referred to, respectively, as the angular engagement position and the angular disengagement position, the engagement angular position being a position in which the cam forces the piezoelectric piston into the engagement position, and the angular disengagement position being a position in which the cam forces the piezoelectric piston into the disengagement position.

3. Analysis device according to claim 2, in which the through-hole (115c) is defined by an inner surface on which the cam (117) is capable of exerting a force to impose either the engaged position or the disengaged position on the piezoelectric piston, advantageously having an elongated shape along a generatrix of the hollow cylindrical body4. Analysis device (100) according to any one of claims 1 through 3, wherein the piezoelectric finger (111) is configured to apply a vibration to the rear surface when the second end (111b) is in contact with the rear surface.

5. Analysis device (100) according to any one of claims 1 through 4, wherein the piezoelectric finger (111) is configured to exert a pressing force perpendicular to the XY plane against the rear face when it is in its engaged position.

6. Analysis device (100) according to any one of claims 1 through 5, wherein said analysis device (100) comprises complementary magnetic means for applying a complementary magnetic field within the at least one chamber (5) of the analysis cartridge (1).

7. Analysis device (100) according to any one of claims 1 through 6, wherein said analysis device (100) further comprises means for analyzing the liquid that may be present in the at least one chamber (5).

8. Analysis device (100) according to claim 7, wherein the analysis means comprise a detector and a radiation source configured to analyze a liquid that may be present in the analysis chamber (5).

9. Analysis device (100) according to any one of claims 1 through 8, wherein the support (101) is perforated so as to make the rear face of the analysis cartridge (1) accessible by the second end (111b) when said cartridge rests with its rear face on said support (101).

10. Analysis device (100) according to any one of claims 1 through 9, wherein said device comprises loading means that cooperate with the support (101) and are configured to position said support (101) in either an analysis position or a loading position, the loading position being a position that allows the analysis cartridge (1) to be inserted into and / or removed from said support (101), while the analysis position is a position that allows the piezoelectric finger (111) to be brought into contact with the rear face of the analysis cartridge (1), advantageously the loading means comprise a worm screw.

11. Analysis device (100) according to claim 10 and claim 7 or 8, wherein the analysis position is also a position that allows the fluid contained in the chamber (5) to be analyzed by the analysis means.

12. Analysis device (100) according to any one of claims 1 through 11, wherein the piezoelectric vibration means comprise a suspension mechanism configured such that the piezoelectric finger (111), when in its engaged position, exerts a predetermined contact force on the rear face, and advantageously, the suspension mechanism comprises a spring mounted in compression and bearing, on the one hand, against the hollow cylindrical body (115) and, on the other hand, a shoulder of piezoelectric foot13. Analysis device (100) according to any one of claims 1 through 12, wherein the support (101) includes wedges configured to cause the rear face of the analysis cartridge (1) to lie in the XY plane14. 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), said additional holding means are specifically configured to hold the analysis cartridge (1) at vents of said cartridge that communicate with the chamber (5), the additional holding means also being configured to seal said vents.