Device for analyzing liquid

Abstract

The present invention relates to an analysis device for biological analysis to detect the presence and / or concentration of a substance in a liquid contained in an analysis chamber of a cartridge. The analysis device specifically includes a piezoelectric vibration member equipped with detachable piezoelectric fingers.

Description

Technical Field

[0001] The technical field of the invention is bioanalytical techniques for detecting the presence and / or concentration of substances (analytes) in liquids, especially biological liquids. The invention more particularly relates to an analytical device configured to engage with an analytical cartridge provided with a chamber in which the liquid to be analyzed is present. Background Art

[0002] Document EP3447492 discloses a method for capturing and detecting substances commonly referred to as "analytes" in liquids (especially biological liquids). The principle of the capture and detection mode implemented by this method is also explained in the paper "Magnetophoretic induced convective capture of highly diffusive superparamagnetic nanoparticles" by Fratzl et al., Soft Matter, 14.10.1039 / C7SM02324C.

[0003] The method comprises in particular the step of mixing a sample consisting of a liquid to be analyzed with magnetic particles. In these aspects, these particles have nanometer-scale dimensions, or more generally submicrometer-scale dimensions, and are coupled to a capture element capable of specifically binding to a substance to be detected and / or quantified. The substance (analyte) may be an antigen and the capture element may be an antibody, but the opposite configuration is also possible.

[0004] During this step a detection element is also introduced into the sample. The detection element may in particular comprise a detection antibody or antigen carrying a photoluminescent (eg fluorescent) label.

[0005] At the end of this step, a complex formed by the capture element, the substance and the detection element is thus formed in the solution. These complexes are then fixed on a support comprising magnetic micro-sources arranged in a specific spatial pattern. The pattern is defined by strong magnetic field areas and weak magnetic field areas that cause large magnetic field gradients. The complexes entrained by the magnetic particles tend to gather on the support at the area with the largest magnetic field norm. Photoluminescent (especially fluorescent) markers can make the specified spatial pattern obvious, which indicates the presence of analyte in the solution. The average intensity (spatially) of this light pattern is usually called a "specific signal".

[0006] In most cases, in particular when the analyte is not present in the sample or when the amount of the analyte in the sample is limited, the unbound detection elements carrying the photoluminescent marker remain dispersed in the solution in a suspended state. They contribute to the formation of a relatively uniform light background. The average intensity (spatially) of this light background forms a signal called the "supernatant signal". In addition to the unbound photoluminescent marker, this light background also consists of the light intensity emitted by all the photoluminescent materials of the sample. Capture elements that are not bound to the analyte and the detection element are also fixed on the support, but do not carry a label; these capture elements do not contribute to the light pattern or the light background.

[0007] The spatial arrangement of the magnetic field microsources in the plane of the support and the light intensity of the pattern displayed by the photoluminescent marker make it possible to carry out the detection and quantification of the analyte in the sample without washing (that is to say without removing the liquid solution after the complex has been fixed on the surface of the support), which is particularly advantageous. In order to allow this detection, the sample and the support surface are illuminated so as to allow the detection of the photoluminescent marker and a digital image is acquired. The digital image thus has a spatially variable intensity (in the image plane) that depends on the intensity of the magnetic field generated by the support. The image is processed to identify this spatial variation and to determine the specific signal and the supernatant signal, the specific signal / supernatant signal ratio making it possible to draw a conclusion on the presence of the analyte in the sample and even to estimate the concentration of the analyte.

[0008] The simplicity of the method, and in particular the absence of washing steps, allows its integration into autonomous portable or transportable immunoassay devices in the field, without pumps or valves and "at the patient's bedside", whereas this type of analysis is traditionally performed in central laboratories.

[0009] In order to allow the application of the detection method, the biological fluid is introduced into a cartridge (for example a disposable cartridge) comprising a plurality of analysis chambers, the cartridge being intended to be inserted into an analysis device. The plurality of analysis chambers makes it possible to carry out several analyses of the biological fluid sample, each analysis being able to be carried out independently on the sample respectively contained in each chamber.

[0010] The cartridge includes a pouring opening for liquid, a plurality of exhaust ports arranged downstream of an analysis chamber, and a channel network for fluidly connecting the opening to the analysis chamber. The biological liquid sample poured into the opening diffuses in the channel network by capillary action, thereby filling the chamber.

[0011] While such a cartridge undeniably offers a number of advantages, it requires a great deal of processing which should be reduced.

[0012] Furthermore, this embodiment requires that the magnetic particles and / or the detection elements are effectively dissolved and mixed.

[0013] One object of the present invention is to propose an analytical device for achieving effective mixing of magnetic particles and / or detection elements present in an analytical chamber of an analytical cartridge. Summary of the invention

[0014] The object of the present invention is achieved by an analytical device for biological analysis to detect the presence and / or concentration of a substance in a liquid, the analytical device comprising:

[0015] - a support for receiving at least one analytical cartridge so that said cartridge rests on said support by one of its surfaces, said cartridge comprising a substantially flat back surface and said back surface coincides with the XY plane, said cartridge comprising at least one chamber capable of containing a liquid intended to be analyzed;

[0016] a piezoelectric vibrating member equipped with a piezoelectric finger extending between two ends, respectively referred to as the first end and the second end, the piezoelectric vibrating member being arranged so that the piezoelectric finger can adopt one or the other of two positions, respectively referred to as the engaged position, in which the second end presses against the support or the back when the cartridge rests on it, and the disengaged position, in which the second end is at a distance from the support and the back so as to allow the cartridge to be removed;

[0017] An engagement member configured to allow the piezoelectric finger to move between one of an engaged position and a disengaged position to the other of these two positions, the engagement member involving a translational movement or a pivoting movement.

[0018] According to one embodiment, the piezoelectric finger is configured to impart a vibration to the back surface once the second end rests against the back surface.

[0019] According to one embodiment, the piezoelectric fingers are configured to exert a bearing force perpendicular to the XY plane against the back surface when in their engaged position.

[0020] According to one embodiment, the analytical device comprises a complementary magnetic component for applying a complementary magnetic field in at least one chamber of the analytical cartridge.

[0021] According to one embodiment, the analytical device further comprises means for analyzing a liquid possibly present in at least one chamber.

[0022] According to one embodiment, the analysis component comprises a detector and a radiation source configured to analyze a liquid that may be present in the analysis chamber.

[0023] According to one embodiment, the support is perforated so as to enable access to the back side of the cartridge through the second end when the cartridge rests with its back side on the support.

[0024] According to one embodiment, the device includes a loading part which is engaged with the support and is configured to impose on the support one or the other of an analysis position and a loading position, wherein the loading position is a position allowing the positioning of the analysis box and / or the removal of the analysis box from the support, and the analysis position is a position allowing the piezoelectric finger to engage against the back of the analysis box. Advantageously, the loading part includes a worm gear.

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

[0026] According to one embodiment, the piezoelectric fingers are mounted on a rod.

[0027] According to one embodiment, the piezoelectric vibration component includes a hollow cylindrical body, which together with a piezoelectric finger forms a piston, namely a so-called piezoelectric piston, the piezoelectric finger is partially accommodated in the hollow cylindrical body coaxially with the hollow cylindrical body, and partially opens outward through an opening in the hollow cylindrical body. The piezoelectric vibration component also includes a guide cylinder, in which the hollow cylindrical body is partially accommodated in a sliding connection.

[0028] According to one embodiment, the engagement means comprise a cam linked to a shaft, which cam acts on the hollow cylindrical body to impart a translational movement thereto in the direction of elongation of the piezoelectric finger, the shaft advantageously being rotationally controlled by means of a motor, in particular a stepper motor.

[0029] According to one embodiment, the piezoelectric vibrating component includes a suspension mechanism configured such that when the piezoelectric finger is in its engaged position, it exerts a predetermined contact force on the back surface.

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

[0031] According to one embodiment, the shaft is mounted such that it can rotate about an axis perpendicular to the direction of elongation of the piezoelectric fingers.

[0032] According to one embodiment, the support comprises wedges configured to force the back side of the cartridge to coincide with the XY plane.

[0033] According to one embodiment, the analysis device comprises additional components for holding the analysis cartridge on the support, which additional holding components are particularly configured to hold the analysis cartridge at the exhaust port of the cartridge and connect it to the chamber, and are also configured to close the exhaust port. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Other features and advantages will become apparent in the following description of an analytical cartridge and an analytical device according to the invention given by way of non-limiting example, with reference to the accompanying drawings, in which:

[0035] [ Figure 1 ] Figure 1 is a schematic perspective view of an analysis box that can be implemented according to the principles of the present invention;

[0036] [ Figure 2 ] Figure 2 is a schematic diagram of the fluid segment according to a cross-sectional plane of the fluid segment parallel to the top surface, Figure 2 In particular, at least one analysis chamber is in fluid communication with the opening via a channel on the one hand and in fluid communication with at least one exhaust port via at least one exhaust channel on the other hand;

[0037] [ Figure 3 ] Figure 3 yes Figure 1 A perspective and exploded schematic diagram of the assay cartridge shown;

[0038] [ Figure 4a ] Figure 4a is at least one analytical chamber along Figure 1 Schematic diagram of a cross-sectional plane (perpendicular to the main surface) of the analysis box;

[0039] [ Figure 4b ] Figure 4b is at least one analytical chamber along Figure 1 Another schematic diagram of a cross-sectional plane (perpendicular to the main surface) of an analytical cartridge, which is implemented with a non-magnetic layer;

[0040] [ Figure 4c ] Figure 4c Can be used for assembly Figure 1 A perspective view of an interlayer membrane of the analytical cartridge shown;

[0041] [ Figure 4d ] Figure 4d is a schematic top view of a detection pattern defined by the magnetization generated by a magnetic layer integrated into the cartridge support, the magnetic field present in the analysis chamber, and the norm of the magnetic field;

[0042] [ Figure 5 ] Figure 5 is a schematic diagram of a liquid-filled analysis chamber including magnetic nanoparticles grafted with capture agents and detection agents suspended for analysis, Figure 5 In particular, the formation mechanism of the complex is shown;

[0043] [ Figure 6 ] Figure 6 is a diagrammatic representation of an analytical device implemented in accordance with the principles of the present invention;

[0044] [ Figure 7a ]

[0045] [ Figure 7b ] Figure 7a and Figure 7b yes Figure 6 Illustration of the interior of the analytical device, with the piezoelectric vibrating element fingers in the disengaged position, Figure 7b is a cross-sectional view;

[0046] [ Figure 7c ] Figure 7c yes Figure 6 a diagram of the interior of the analytical device with the fingers of the piezoelectric vibrating member in an engaged position;

[0047] [ Figure 8 ] Figure 8 The support that can be used within the scope of the present invention is illustrated by way of example according to a perspective view. In particular, the support shown in this figure can accommodate two analysis boxes;

[0048] [ Fig. 9 ] Fig. 9 yes Figure 8 An illustration of a support member shown in and accommodating an analytical cartridge at one of its locations;

[0049] [ Fig.10 ] Fig.10 is a diagram of a piezoelectric finger that can be implemented within the scope of the present invention;

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

[0051] [ Fig.12 ] Fig.12 yes Fig.11 An illustration of a hollow cylindrical body used in a piezoelectric vibration component according to a perspective view;

[0052] [ Fig.13 ] Fig.13 yes Fig.11 Illustration of a guide cylinder used in a piezoelectric vibration component according to a perspective view. DETAILED DESCRIPTION

[0053] Figure 1 An analytical cartridge 1 is shown for analyzing a substance (hereinafter referred to as "analyte") that may be present in a liquid, more particularly a biological liquid.

[0054] In these aspects, the analytical cartridge 1 is adapted to receive a sample of a liquid, such as a biological liquid, in order to detect the presence of a given analyte in said liquid.

[0055] The analysis box 1 thus comprises at least one microfluidic analysis chamber 5. In particular, the analysis box may comprise between 1 and 10 (e.g. 5) analysis chambers 5. It should be understood that the analysis chamber itself may comprise a plurality of shells arranged in series. However, the remainder of the present invention will be limited to describing a chamber having a single shell and referred to by the word "chamber".

[0056] The cartridge 1 may comprise a gripping end 1a for gripping it. The gripping end 1a may be labeled, for example provided with a barcode or a QR code, allowing identification and tracing of the assay by means of the cartridge 1 in question. The identification means may alternatively comprise an "RFID" chip.

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

[0058] The active section 1 b is generally planar in shape and comprises two main faces, referred to as the top face and the bottom face.

[0059] The cartridge 1 may comprise at least one pouring opening 2, which allows liquid to be introduced into the cartridge 1. This opening 2 in particular opens into the top surface of the active section 1 b.

[0060] Specifically, the opening 2 is in fluid communication with at least one analysis chamber 5. In particular, the active section comprises at least one microfluidic channel 4, which provides 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 that the liquid poured into the opening 2 flows and is distributed toward the at least one analysis chamber.

[0061] The analysis box 1 may further include at least one exhaust port 3 ( Figure 1 and Figure 2 The at least one exhaust port 3 is particularly configured to allow evacuation of air that may be present in the at least one analysis chamber 5 when the at least one analysis chamber 5 is filled with liquid. In particular, the fluid communication between the at least one analysis chamber 5 and the at least one exhaust port 3 is ensured by at least one exhaust channel 4'.

[0062] Thus, in operation, a liquid sample is introduced into the opening 2, for example by means of a pipette. The sample then flows via the at least one microfluidic channel 4 into the at least one analysis chamber 5. Air that may be present in the at least one analysis chamber 5 is evacuated during the flow of the liquid in said analysis chamber 5 to the at least one exhaust port 3.

[0063] In the case of multiple analysis chambers 5, the microfluidic channels 4 can be arranged so that the liquid sample flows simultaneously or sequentially in each chamber 5. "Sequential flow" is understood to mean that the analysis chambers 5 are filled according to a predetermined order. Specifically, according to this principle, the flow in a given chamber only starts when the analysis chamber located before it in the filling order is completely filled.

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

[0065] Figure 1 The analytical cartridge 1 shown may also include a reservoir 2' located above the opening 2, the volume of which is equal to the volume of the microfluidic network formed by at least one microfluidic channel 4, at least one analytical chamber 5 and at least one exhaust channel 4'. In this regard, the volume may be between 5 mm 3 With 500mm 3 More specifically, between 20 mm 3 With 100mm 3 between.

[0066] Similarly, according to the principle of communicating vessels, the peripheral wall rises next to at least one exhaust port 3 in order to retain excess volume of liquid. Advantageously, the height of the peripheral wall is at least equal to the height of the reservoir 2' in order to prevent liquid from escaping from the analytical cartridge 1. This arrangement reduces the risk of health problems or even damage to the analytical device (described below) into which the analytical cartridge 1 is to be inserted.

[0067] By way of example, the cartridge 1 may have a width and a length measuring between 2 cm and 10 cm, and a thickness between 4 mm and 10 mm. The at least one analysis chamber 5 may have a thickness of typically between 1 mm. 3 With 50mm 3 between, advantageously between 5 mm 3 With 25mm 3 The volume in between is used to receive the sample.

[0068] according to Figure 3 By way of non-limiting example, the cartridge 1 may be formed by a support 6 and an upper cover 7 covering the support 6. The support 6 and the upper cover 7 are assembled together in particular by placing their so-called "main" surfaces facing each other.

[0069] At least one analysis chamber 5, at least one microfluidic channel 4 and at least one exhaust channel 4' form the microfluidic network of the analytical cartridge 1. This microfluidic network is defined in particular by grooves 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 that are to be assembled together.

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

[0071] Likewise, at least one analysis chamber 5 is also delimited by the main surfaces of the support 6 and the cover 7, which form the chamber bottom 5a and the chamber ceiling 5b, respectively ( Figure 4a and Figure 4b ). At least one chamber 5 further comprises a chamber side wall 5c extending from the chamber bottom 5a toward the chamber ceiling 5b. However, it should be understood that at least one analysis chamber 5a may not have a ceiling, for example, forming an open well at the active section.

[0072] It will also be appreciated that the sidewall of at least one chamber may be deformable.

[0073] The upper cover 7, at least for the portion overhanging the at least one analysis chamber 5, may be made of a material transparent to a photoluminescent signal that can be emitted by a detection agent described below. The material forming the upper cover 7 may include at least one material selected from the following: a plastic material based on, for example, polycarbonate, cyclic olefin copolymer or polystyrene, or glass.

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

[0075] Therefore, microfluidic networks such as Figure 2 The microfluidic network shown extends in the main plane of the analysis box 1. Its dimensions are in the millimeter range, that is, the width of the channels 4, 4' and the analysis chamber 5 is generally between 0.1 mm and 10 mm. The height of these elements, that is, the distance separating the bottom and the top plate, is also between 0.1 mm and 10 mm. The liquid that can be introduced at the opening 2 diffuses in the microfluidic network by capillary action.

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

[0077] Alternatively, it may be possible to arrange at least one first cluster on the ceiling 5b of at least one chamber 5. Such a configuration may significantly facilitate resuspension of the first cluster when the first cluster is subjected to magnetic forces due to the presence of the magnetic layer 6b described below (described below).

[0078] The first cluster may advantageously have a volume between 0.1 μL and 5 μL and advantageously between 0.5 μL and 2 μL.

[0079] "Keeping together" is to be understood as meaning a collection of nanoparticles that are bound together. This coagulation between nanoparticles can be direct or indirect. Direct coagulation can be provided in particular by dried or freeze-dried nanoparticles, while indirect coagulation can be ensured by an encapsulating material. In this respect, the encapsulating material can include sugars (trehalose, glucose, etc.), viscous solutions (e.g. Tween) or glycerol.

[0080] The nanoparticles remain in the form of clusters between them, ensuring better stability over time.

[0081] The implementation of encapsulating materials makes it possible to facilitate the suspension of the nanoparticles, as presented below in the rest of the description.

[0082] The size of the magnetic nanoparticles 9a can be nanometer-sized, usually between 25nm and 500nm, preferably between 100nm and 300nm. The shape of the magnetic nanoparticles 9a can be roughly spherical. They have superparamagnetic properties and biocompatibility. They can also be covered with a polymer (polystyrene type) that has been surface-treated, which allows the polymer to be functionalized with, for example, Ac-type or Ag-type proteins. The controlled amount of these particles is such that once filled with the liquid to be analyzed, their concentration in the chamber volume is between 10 6 Particles / mL and 10 12 particles / mL, preferably between 10 9 Particles / mL and 10 11 particles / mL.

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

[0084] The analysis box 1 may also include at least one second cluster 10 ( Figure 4a and Figure 4b At least one second cluster 10 is formed in particular by a detection agent 10a bound therebetween ( Figure 5 ).

[0085] It should be understood that, without specifying, the first cluster 9 and the second cluster 10 may form a single cluster. In addition, both the first cluster 9 and the second cluster 10 may be deposited on the chamber wall.

[0086] Advantageously, the first cluster 9 and / or the second cluster 10 are based on a surface energy density associated with a hydrophobic surface. As is known, the surface energy density can be determined by measuring the contact angle of a water droplet, wherein the water droplet is arranged 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 considered to be hydrophobic. On the contrary, a contact angle less than 90° indicates a high surface energy density, a so-called hydrophilic surface. Taking into account the hydrophobic surface makes it possible to impose a relatively spherical shape on one and / or the other of the first and second clusters.

[0087] The second cluster may advantageously have a volume between 0.1 μL and 5 μL and advantageously between 0.5 μL and 2 μL.

[0088] Both the at least one first cluster 9 and the at least one second cluster 10 are intended to allow the capture or even immobilization of an analyte 11 present in a liquid, as well as the detection or even quantification of the presence of said analyte 11. To this end, the analyte 11 present in the liquid, in the presence of the detection agent 10a and the magnetic nanoparticles 9a to which the capture agent 9b is grafted, forms a complex 12 with these elements ([ Figure 5 ]).

[0089] The magnetic nanoparticles are intended to separate the complexes, while the detection agents are used to detect the complexes.

[0090] Thus, using the analytical cartridge 1 for detecting and / or quantifying an analyte in a liquid involves pouring a sample of the liquid into at least one analytical chamber via the opening 2 .

[0091] Forming the complex 12 also involves suspending the elements forming the first cluster 9 and the second cluster 10 in the liquid sample present in the analysis chamber 5 .

[0092] The levitation operation may include, in particular, separating the first cluster and the second cluster from the bottom of the chamber 5a, and separating the elements from each other so as to disperse them in the sample. To this end, the piezoelectric vibration member 110 described below may be used.

[0093] These piezoelectric vibrating elements 110 are particularly suitable for applying vibrations to the chamber bottom 5a. This vibration generates an acoustic pressure field in the liquid present in the analysis chamber 5, thus suspending the elements forming the first cluster 9 and the second cluster 10.

[0094] According to a first variant, the vibrations can be applied at a fixed frequency, for example a fixed frequency between 5 kHz and 2 MHz, advantageously between 20 kHz and 200 kHz. Still according to this first variant, the vibrations can be close to the resonant frequency of the analysis chamber 5 ("close to the resonant frequency" should be understood to mean a frequency within + / -15%, advantageously within + / -10%, even more advantageously within + / -5% of the resonant frequency of the analysis chamber). Advantageously, the resonant frequency of the analysis chamber 5 is approximately 50 kHz, approximately 80 kHz, or approximately 110 kHz.

[0095] The analysis chamber with such a resonant frequency may include a rectangular cross section along a cross-sectional plane perpendicular to the back of the analysis box, which ends at each of the two ends at a mouth portion having a triangular cross section along the same plane. The length and width of the rectangular cross section are 8.4 mm and 2.4 mm respectively, while the base and height of the triangular cross section are 2.4 mm and 4 mm respectively. The height of the analysis chamber is 390 μm.

[0096] According to a second variant, the vibration can be applied in a cyclic form, for example in a repeated cycle. In these aspects, one cycle can include a sweep of increasing or decreasing frequency, more specifically a sweep of frequency around the resonance frequency of the analysis chamber. A complete frequency sweep can last between 10 and 200 seconds. In particular, the frequency sweep includes a stepwise increase or decrease in frequency.

[0097] In particular, each step corresponds to maintaining the frequency for a period of time, which may be between 2 and 10 seconds, in order to allow sufficient movement of the liquid to achieve a minimum mixing effect.

[0098] By way of example, one cycle may involve a frequency sweep from 110 kHz to 120 kHz, or vice versa, from 120 kHz to 110 kHz. Such a sweep can be performed in steps of 1 kHz, with each step of vibration being held for a few seconds, in particular 2 seconds.

[0099] Again by way of example, the vibration sequence may include a repeating base sequence including 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, with the vibration being held for 2 seconds at each step.

[0101] The second cycle may include a frequency sweep from 110 kHz to 119 kHz in 1 kHz steps, with the vibration being held for 2 seconds at each step.

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

[0103] It is also possible to consider applying vibrations continuously or in the form of one or more pulses at a fixed frequency (e.g. approximately equal to one of the following frequencies: 56 kHz, 74 kHz, 80 kHz, 110 kHz). The fixed frequency is advantageously equal to or at least close to the natural frequency of the analysis chamber (the so-called "natural frequency" means the set formed by the resonant frequency and its harmonics).

[0104] Particularly advantageously, the side wall 5c may be designed to generate vortices which favour mixing in the sample as it circulates in the analysis chamber.Such a design of the side wall 5c may comprise a crenellated surface.

[0105] Particularly advantageously, the gas, more particularly air, is initially trapped in the side wall 5 c of at least one chamber 5 .

[0106] Under the effect of mechanical stress applied to the at least one analysis chamber, the trapped gas can be released, thereby generating bubbles on the side walls of the at least one chamber as soon as the liquid sample is present in the at least one chamber 5. The mechanical stress can be applied in particular to the back side of the cartridge 1.

[0107] According to one embodiment, the side wall 5c of 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 may initially be trapped in grooves 5e opening into the side wall ( Figure 4c ).

[0109] The groove 5e may have a length between 100 μm and 1000 μm and a cross section with a maximum dimension between 100 μm and 400 μm.

[0110] The cross-section of the groove may include at least one shape selected from square, rectangular, and circular.

[0111] According to the invention, once gas bubbles have been generated (in particular under the effect of the aforementioned stresses), the acoustic pressure field generated by the vibrations of the chamber bottom allows these gas bubbles to vibrate in the liquid present in the analysis chamber.

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

[0113] However, this effect can be optimized by forcing the bubbles to vibrate at a frequency close to their resonant frequency ("close to the resonant frequency" should be understood to mean a frequency within + / - 15%, advantageously within + / - 10%, even more advantageously within + / - 5% of the resonant frequency of the bubbles). In fact, under these conditions, the contribution of the bubbles to the mixture is exacerbated, especially when some of the bubbles are able to transfer energy through their implosion and the resulting shock wave.

[0114] To this end, the holes and / or grooves for trapping the gas may be configured such that bubbles can be generated having a resonance frequency close to the resonance frequency of the analysis chamber.

[0115] Specifically, for a given slot size, the bubble size may be in the range of 50 μm to 500 μm. For bubble sizes in this range, the resonant frequency is between 20 kHz and 500 kHz.

[0116] Still according to the present invention, the analysis box 1 may include a magnetic layer 6b ( Figure 4a ), which is arranged to fix 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 serves to fix the complex 12. The magnetic layer 6b is advantageously microstructured so that the magnetic nanoparticles fixed on the bottom of the analysis chamber 5 form a predefined pattern.

[0117] In these aspects, the magnetic layer 6b may include at least a first region 6b1 and a second region 6b2 that are repeatedly juxtaposed. More specifically, the first region 6b1 may have a magnetic polarization along a first direction, and the second region 6b2 may have a zero magnetic polarization or a magnetic polarization along a second direction different from the first direction (preferably 180° different). Figure 4a ).

[0118] The support 6 may be arranged in particular such that it comprises, from the main surface to the back surface, an interlayer film 6d, a magnetic layer 6b and a rigid substrate 6a. It should be understood that the magnetic layer 6b does not necessarily extend over the entire surface of the substrate 6a ( Figure 3 , Figure 4a and Figure 4b ).

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

[0120] The magnetic layer 6b may include a magnetic composite material, such as ferrite, randomly distributed in a polymer or oriented along a pre-oriented axis. The magnetic layer 6b may be similar to a conventional magnetic recording tape. In the latter case, the microstructuring of the magnetic layer is associated with magnetic encoding (particularly via a magnetic recording / playback head). More specifically, the microstructuring in the latter case means the generation of magnetic regions that may differ from one region to another in terms of orientation and / or amplitude in terms of magnetization. For example, two adjacent regions may have two opposite orientations, more specifically 180°.

[0121] The substrate 6a may further include a non-magnetic layer 6c (or a plurality of such films) sandwiched between the magnetic layer 6b and the interlayer film 6d. The non-magnetic layer 6c is optional and is designed to keep the magnetic layer 6b away from the bottom of the analysis chamber 5.

[0122] The term "non-magnetic layer" refers to a layer with a magnetic susceptibility of zero or less than 10 -3 (absolute value) layer.

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

[0124] In the example shown above, the interlayer film 6d defines a microfluidic network. Specifically, the interlayer film 6d is cut according to a pattern corresponding to the microfluidic network. Figure 4c The interlayer membrane 6d shown. When this interlayer membrane 6d is assembled to the substrate 6a to form the support 6, the substrate thus has grooves that reproduce the cutout pattern of the membrane 6d. These grooves, optionally combined with complementary grooves formed in the upper cover 7, form the microfluidic network of the cartridge 1.

[0125] Particularly advantageously, the interlayer film 6d is an adhesive film, also enabling the upper cover 7 to be assembled and hermetically sealed to the support 6 at the contact surface with the support 6 (i.e. around the groove). For example, the interlayer film can be a double-sided adhesive film, thereby ensuring its assembly to the substrate 6a and the upper cover 7 at the same time. As is known, such an interlayer film 6d can consist of a strip (e.g. a plastic strip) coated on both sides with an adhesive material.

[0126] Still advantageously, when mechanical stress is applied to the bottom of the chamber, gas or bubbles may be generated due to the release of gas trapped in the interlayer membrane. Therefore, the membrane may be porous and / or include grooves formed, for example, when cutting a pattern corresponding to the microfluidic network.

[0127] Returning to the description of the magnetic properties of the analysis box, the magnetic layer 6b includes two different directions (in Figure 4a and Figure 4b A series of regions 6b1 and 6b2 with opposite polarization. Figure 4d , which shows a top view of the magnetic layer 6 b , wherein in the example shown, the magnetically polarized regions extend in a straight line along the main direction P.

[0128] Areas of relatively high magnetic field strength, called attraction zones, are observed at the interfaces between zones of different polarization. The attraction zones are arranged in particular in the form of a plurality of lines Za oriented along the main direction P. The specific arrangement of these lines in combination defines a detection pattern.

[0129] It will be appreciated that the in-line arrangement adopted in one example only forms a special case of a detection pattern. The cartridge 1 is more generally provided with magnetically polarised areas which define a well-defined detection pattern, but whose configuration may be freely chosen.

[0130] The field Bc generated by the magnetic layer 6b and its norm are also Figure 4d As will be explained below, it may be useful to add an additional (or complementary) external field Bext to the field generated by layer 6b. Figure 4d This external field Bext combined with the field Bc generated by this layer is shown, as well as 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 attraction zones Za generated when only the field provided by the magnetic layer 6b is present. However, in each case, these attraction zones are arranged along a line Za oriented in the main direction P, or more generally according to a detection pattern, the characteristics of which are fully determined.

[0131] In the case where the analysis chamber 5 has the dimensions indicated above, it is possible to consider forming a detection pattern comprising between 2 and 50 lines, said lines having a thickness between 1 μm and 150 μm, advantageously between 5 μm and 30 μm, and being separated from each other by a spacing between 5 μm and 300 μm, advantageously between 25 μm and 150 μm.

[0132] Based on this description, the inventors have calculated the surface gradient at the surface of a non-magnetic layer having a thickness of about 55 μm and located on the magnetic layer.

[0133] The micromagnets in the magnetic layer on which the nonmagnetic layer lies are 50 μm wide and 10 μm high. These micromagnets are characterized by planar polarization and alternate with each other. In this calculation, a NdFeB magnetic field source with a remanence of 1.2 T below the magnetic layer is also used. This applies a magnetic field with an amplitude between 0.005 Tesla and 0.3 Tesla.

[0134] As part 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 by plus or minus an order of magnitude. As a result of these gradients, magnetic forces are exerted on the particles. This force is able to hold the magnetic particles (especially clusters) and also contributes to the immobilization of the magnetic particles (described at the end of this application).

[0135] Thus, when a liquid sample is introduced into the analysis box 1, the sample flows through the microfluidic channel 4 to fill at least one analysis chamber 5 and then diffuses through the exhaust channel 4'. Vibration and mechanical stress are applied to the back of the analysis box 1. Bubbles are then generated due to the release of gas under the action of mechanical stress. The acoustic pressure field generated by the vibration applied to the bottom suspends the elements forming the first cluster and the second cluster, and if necessary, mixes the elements forming the first cluster and the second cluster. In addition, the acoustic pressure field can vibrate the bubbles.

[0136] The vibration of the bubbles also helps to a certain extent the detection agent 10a and the capture agent 9b associated with the magnetic nanoparticles 9a to suspend and mix in the liquid sample present in the analysis chamber 5. During the subsequent reaction time, when the analyte is present in the sample, a complex comprising at least one capture element, at least one magnetic nanoparticle, at least one analyte and at least one detection element is formed. These complexes are fixed on the support 6 of the analysis chamber 5 by gathering in a preferred manner at the maximum value of the norm of the magnetic field intensity (caused by the microsource and optionally the external magnetic field), so as to be arranged according to the detection pattern defined by the magnetic layer 6b. Excess detection elements remain suspended in the sample.

[0137] It can be provided that each analysis chamber 5 of the cartridge 1 is prepared to receive capture elements and detection elements of different nature in order to perform multiple analyses of a liquid sample introduced into the analysis cartridge 1. It can also be provided that the detection pattern encoded by the portion of the magnetic layer 6b arranged at the chamber 5 is different from one chamber to another.

[0138] It is also conceivable to include a magnetic layer comprising regions without magnetic zones, and to form the first cluster directly above this magnetic layer (thus enabling resuspension of magnetic nanoparticles from the first cluster to be facilitated).

[0139] In each case, the presence of an analyte in a sample retained in the analysis chamber 5 causes the formation of a detection pattern defined by the magnetic layer 6b.

[0140] The present invention also relates to an analytical device 100 ( Figure 6 ).

[0141] The analysis device 100 comprises in particular a support 101 intended to receive at least one analysis cartridge 1 in order to analyze a liquid sample contained in at least one analysis chamber 5 ( Figures 7a to 7c ). More specifically, the support 101 is designed to receive the analysis cartridge 1 so that the analysis cartridge 1 rests on the support 101 by one of its surfaces. In the remainder of the present application, it is assumed that the analysis cartridge rests on the support with its back side. However, this last aspect does not limit the invention, and the skilled person will be able to consider that the analysis cartridge rests on the support with one of its surfaces opposite to the back side.

[0142] In these aspects, Figure 8 A support 101 that can be implemented within the scope of the present invention is shown. In particular, the support 101 shown in this figure can accommodate two analysis cartridges.

[0143] The support 101 may also be configured to allow the analysis cartridge 1 to be inserted by sliding along the direction "A" ( Figure 8 ).

[0144] Specifically, the support 101 includes a bottom, a so-called support bottom 101 a , and side walls 101 b and 101 c , which are configured to guide the insertion of the analysis cartridge 1 .

[0145] The snap-fit ​​component 102 may also be arranged on the support bottom 101 a . The snap-fit ​​component 102 is particularly configured to engage with the back side of the analysis cartridge 1 so as to hold the analysis cartridge on the support 101 .

[0146] The support 101 is also perforated and includes a window 103 formed on the support bottom 101a for providing access to the back of the analysis box when the analysis box 1 is inserted into the support 101. Specifically, the window 103 can be positioned directly above the analysis chamber 5 of the analysis box 1 arranged on the support 101.

[0147] Alternatively, the support may be configured to direct the vibrations applied by the piezoelectric fingers. In these aspects, the support may include components for distributing the vibrations applied by the piezoelectric fingers on the cartridge. These distribution components may be specifically arranged to direct the vibrations at at least one analysis chamber, and more specifically at each analysis chamber when there are multiple analysis chambers.

[0148] When the analysis box 1 is placed on the support 101, the back surface of the analysis box coincides with (ie, coplanar with) the XY plane. Specifically, the XY plane is parallel to the support bottom 101a. The XY plane can be, for example, a horizontal plane.

[0149] The side walls 101b and 101c further include an anti-slip portion 104 ( Fig. 9 ).

[0150] The anti-slip portion 104 (or wedge) together with the snap member 102 ensures that the analysis box 1 is held in place on the support 101 and that the back of the box 1 is coplanar with the XY plane. These retaining members as described above are configured to ensure that the XY plane is coplanar with the back of the analysis box. However, the present invention is not limited to the described members, and a person skilled in the art will be able to implement any member that ensures that the XY plane is coplanar with the back of the analysis box.

[0151] Spring components can be arranged on the support bottom 101a. These spring components are particularly configured to press the analysis box 1 against the anti-slip portion 104, thereby ensuring that the XY plane is coplanar with the back of the analysis box. The spring components can include rods. However, this last aspect does not limit the scope of the present invention, and the technician will be able to implement any other type of components that exhibit this function.

[0152] The analysis device 100 may also comprise additional components for holding the analysis cartridge on the support. These additional holding components are particularly configured to hold the analysis cartridge at its exhaust port, in particular so as to close said exhaust port. This closing of the exhaust port significantly prevents the liquid from being pumped out of the chamber, and therefore the vibration amplitude applied by the piezoelectric finger can be increased. Therefore, this latter aspect makes it possible to envisage shorter mixing times.

[0153] The analysis device 100 also includes a stop rail. The stop rail is particularly arranged to be opposite to the surface of the analysis box opposite to the back side. Specifically, the stop rail is arranged to limit the displacement of the analysis box when the piezoelectric finger contacts the back side. The support may also include one or more notches formed on its side walls 101a and 101b to allow contact between the stop rail and the analysis box (so-called stop contact).

[0154] The analysis device 100 further comprises a piezoelectric vibration component 110 arranged to apply vibrations to the bottom of the analysis chamber in order to generate an acoustic pressure field in a liquid that may be present in the at least one analysis chamber 5 .

[0155] The piezoelectric vibrating component 110 may include a transducer, in particular an Elliptec TM Transducer type: elliptical transducer.

[0156] Alternatively, the piezoelectric vibration component 110 may include a piezoelectric stack.The piezoelectric vibration component 110 may include a so-called Langevin transducer (a Langevin transducer consists of a ceramic stack held between two metal parts that clamp an assembly together).

[0157] In these respects, the inventors were able to demonstrate that these linear transducers have good hybrid dynamic characteristics.

[0158] Bolt-on Langevin ultrasonic transducers are also very effective.

[0159] Particularly advantageously, the piezoelectric vibrating component 110 includes a piezoelectric finger 111 extending between a first end 111a and a second end 111b. It should be understood that, without specifying, a "finger" is a generally elongated element insofar as it extends between the first end and the second end. Typically, the piezoelectric finger can be cylindrical in shape. However, the invention is not limited in this respect, and the skilled person will be able to consider other shapes. It should be understood that the second end can be pointed, flat, rounded, or include multiple contact points (rake-shaped).

[0160] like Fig.10 As shown in , the piezoelectric finger 111 may include a piezoelectric stack 112 sandwiched between a first element 113 and a second element 114, both of which are substantially 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 should be understood that the first element, the piezoelectric stack and the second element are mechanically integrated with each other and in this way ensure prestressing between these different elements. When the second end is pressed against the back surface or the support, the prestress may be at least 10 times the support force applied by the second end. In particular, the prestress improves the coupling between the piezoelectric stack and the elements 113 and 114, thereby limiting the influence of the support force on the vibration mode of the stack 112. In other words, the prestress may be greater than 20MPa, advantageously greater than 35MPa, and even more advantageously greater than 50MPa. The prestress improves the efficiency of the transmission of the vibration generated by the piezoelectric finger to the analytical box.

[0161] The piezoelectric vibrating component 110 is arranged so that the piezoelectric finger 111 can adopt one or the other of two positions known respectively as the engaged position and the disengaged position.

[0162] Specifically, the engagement position is the position where the second end abuts against the back face when the cartridge rests on the support, whereas the disengagement position is the position where the contact end is at a distance from the back face to allow removal of the cartridge 1 .

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

[0164] Advantageously, when the piezoelectric fingers are in their engaged position, the bearing forces exerted by said fingers on the back surface are perpendicular to the YZ plane.

[0165] The analytical device 100 may further include an engagement component configured to allow the piezoelectric finger to move between one of the engaged position and the disengaged position to the other of the two positions.

[0166] By way of example, and as Figure 7a , Figure 7b and Figure 7cAs shown, the piezoelectric vibration component 110 may include a rod 110a on which the piezoelectric finger is mounted. Specifically, the rod 110a is mounted so that it can rotate around an axis that is integral with the analysis device 100. Specifically, in Figure 7a and Figure 7b In the embodiment, the rod 110a forces the piezoelectric finger 111 into its disengaged position. In other words, the second end 110a of the piezoelectric finger 111 is at a distance from the back of the analysis box resting on the support 101. Figure 7c In the embodiment, the piezoelectric finger 111 is in its engaged position so that its second end 110b is in contact with the back side of the analysis cartridge 1. According to this aspect, the engagement member may include a motor.

[0167] Fig.11 An example of a piezoelectric vibration component is shown in which the transition from one of the engaged position and the disengaged position to the other of the two positions involves a translational motion.

[0168] In this example, the piezoelectric finger obviously moves in a direction parallel to its elongation direction. More specifically, the translational movement can be perpendicular to the XY plane. Therefore, it should be understood that, without specifying and according to this last aspect, the piezoelectric finger can be mounted perpendicular to the XY plane.

[0169] according to Fig.11 and Fig.12 In the example shown, the piezoelectric vibration component comprises a hollow cylindrical body 115, which together with the piezoelectric finger 111 forms a piston, the so-called piezoelectric piston. Specifically, in this example, the piezoelectric finger 111 is partially accommodated in the hollow cylindrical body 115 coaxially with the hollow cylindrical body. In other words, a section of the piezoelectric finger opens outward through an opening 115a in the hollow cylindrical body 115. It should be understood that the section of the piezoelectric finger passing through the opening includes a second end 111b. The hollow cylindrical body 115 includes a side wall 115b that gives it a cylindrical shape.

[0170] The piezoelectric vibration component also includes a guide cylinder 116 ( Fig.11 )and( Fig.13 ), wherein the hollow cylindrical body is partially accommodated in a sliding connection ( Fig.11 Specifically, the hollow cylindrical body 115 is mounted in the guide cylinder 116 such that the elongation axis of the piezoelectric finger coincides with the rotation axis of the guide cylinder 116 .

[0171] Thus, by translating the piezoelectric piston in the guide cylinder parallel to the axis of rotation of the guide cylinder, the piezoelectric finger can adopt one or the other of the engaged or disengaged positions.

[0172] According to the present invention, the transition from one of the engaged position and the disengaged position to the other is controlled by the engagement member. Fig.11 As shown, these engaging parts include (by fixed connection) a cam 117 linked to axle 118. Specifically, axle 118 is installed so that it can rotate around the fixed axis of analytical device 100. More specifically, axle 118 passes through the wall of guide cylinder 116 (this axle is particularly pivotally connected to guide cylinder), and is configured to drive cam 117 when it rotates. Specifically, cam 117 can include a cylindrical block offset relative to axle 118. However, the present invention is not limited to this type of cam, and the technician will be able to consider the shape outside the rotating cylinder.

[0173] The cam 118 engages with at least one through-opening 115c arranged in the side wall of the hollow cylindrical body 115 so as to apply one or the other of the engaged position and the disengaged position to the piezoelectric finger under the sole action of the cam 117. In particular, at least one through-opening 115c is arranged in the side wall of the hollow cylindrical body 115 and is defined by an inner surface to which the cam 118 is able to apply a force to apply one or the other of the engaged position and the disengaged position to the piezoelectric finger. In particular, the through-opening 115c has a shape suitable for allowing a transition from one or the other of the engaged position and the disengaged position to the other of the two positions. By way of example, the through-opening may have an elongated shape along the guide portion of the hollow cylindrical body.

[0174] Thus, during operation, the cam is able to assume two angular positions around an axis coinciding with the shaft, referred to as an angular engagement position and an angular disengagement position, respectively, wherein the angular engagement position is the position where the cam applies the engagement position to the piezoelectric piston, and the angular disengagement position is the position where the cam applies the disengagement position to the piezoelectric piston.

[0175] The arrangement of the engagement components as described above makes them more compact than systems known to the skilled person.

[0176] It will be appreciated that the cam and shaft extend along an axis that is perpendicular to the axis of elongation of the piezoelectric fingers.

[0177] It will also be appreciated that the shaft may be rotated by means of a motor.

[0178] According to a particularly advantageous embodiment, the piezoelectric vibrating component comprises a suspension mechanism configured so that, once the piezoelectric finger is in its engaged position, a predetermined contact force is applied to the back surface. In other words, the suspension mechanism is configured to allow the piezoelectric finger in the hollow cylindrical body to retract once it comes into contact with the back surface, so as to limit the force applied by said finger on the back surface to the predetermined contact force.

[0179] According to a particularly advantageous embodiment, the suspension mechanism comprises a compression mounted spring 119 which presses on the one hand against the hollow cylindrical body and on the other hand against a shoulder 111 c of the piezoelectric foot. The shoulder can in particular be formed by the edge of a sleeve in which the piezoelectric finger is attached. In the present description it is assumed that the shoulder is an integral part of the piezoelectric finger.

[0180] In particular, when no stress is applied, the suspension mechanism holds the piezoelectric finger 111 in abutment against a stop on the hollow cylindrical body from the first end to the second end, for example, by its shoulder, in a direction referred to as the direct direction. The piezoelectric finger is partially retracted once it comes into contact with the back of the analysis box, thereby applying a compressive force to the spring 119 in a direction opposite to the forward direction. By selecting an appropriate spring constant for the spring 119, a predetermined contact force (or supporting force) can be applied to the back of the analysis box. In an alternative and / or complementary manner, the piezoelectric piston may include components for adjusting the spring compression. These adjustment components may in particular include a screwing system or a screwing washer engaged with the hollow cylindrical body. However, the present invention is not limited to these screwing systems, and the skilled person will be able to consider any other technical solution for adjusting the spring compression.

[0181] Advantageously, the support force may 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 may be applied at a distance between 4 mm 2 With 64mm 2 on the surface area between.

[0182] Therefore, for the 4mm 2 or 64mm 2 The 1N supporting force on the surface area exerts a pressure of approximately 5000Pa and 156.25Pa respectively.

[0183] Comparable to this, for the 4mm 2 or 64mm 2 With a 50N bearing force on the surface area, the applied pressure is approximately 125kPa and 7812.5Pa respectively.

[0184] The movement of the chamber bottom under the supporting force to initiate mixing and optionally gas bubble generation may be between 0.2 μm and 4 μm, more advantageously between 2 μm and 4 μm.

[0185] The analysis device 100 can also be configured to move the analysis box 1 and / or the piezoelectric vibration component 110 so that each analysis chamber can be matched with the piezoelectric vibration component continuously, thereby continuously and specifically applying vibration to the bottom of each analysis chamber. Therefore, the analysis box can be moved laterally to face the piezoelectric vibration component. In a complementary manner, the piezoelectric vibration component can be arranged to move in the horizontal direction so that the finger of the component is in contact with the back of the analysis box.

[0186] Thus, by way of example, the analysis device comprises a worm gear which engages with the support and is configured to impose one or the other of an analysis position and a loading position on the support. The loading position is a position for placing an analysis cartridge and / or removing the analysis cartridge from the support, while the analysis position is a position for engaging the piezoelectric finger against the back of the analysis cartridge. Alternatively, a rack and pinion implementation may be considered.

[0187] The analysis device 100 may comprise a complementary magnetic component for applying a complementary magnetic field in at least one analysis chamber of the analysis cartridge. The complementary component is advantageously implemented when taking into account the non-magnetic layer 6c.

[0188] The analysis device 100 may also comprise components for analyzing a sample present in at least one analysis chamber 1. These analysis components 120 are coupled to the detection agent 10a. In these aspects, the analysis components 120 may comprise optical components, and more particularly an epifluorescence microscope.

[0189] More specifically, the analysis component 120 is configured to locate / detect the complexes 12 fixed on the bottom of the analysis chamber 5 by the magnetic layer 6b. Specifically, these fixed complexes form a pattern determined by the arrangement of the magnetic regions of the magnetic layer 6b.

[0190] Furthermore, as long as the detection agent associated with the immobilized complex 12 carries a label, the immobilized complex 12 can be revealed.

[0191] Specifically, the label carried by the detection agent can be a photoluminescent label, such as a fluorescent label.

[0192] Thus, the analyzing part of the analyzing device may advantageously comprise a radiation source 121 and a detector 122. The radiation source is particularly intended to induce the emission of a photoluminescent signal by the marker, whereas the detector is configured to collect said photoluminescent signal.

[0193] As described in the present invention, piezoelectric vibrating components can be used to mix and / or concentrate liquids and / or elements contained in the liquids for analytical purposes. These piezoelectric vibrating components can also be implemented to move liquids, such as from one chamber to another chamber (the two chambers are linked by a fluid channel) to pump liquids into chambers such as analytical boxes.

Claims

1. An analytical device (100) for biological analysis to detect the presence and / or concentration of a substance in a liquid, the analytical device comprising: - a support (101) for receiving at least one analysis cartridge (1) such that the analysis cartridge (1) rests on the support (101) by one of its surfaces and the analysis cartridge comprises a substantially flat back surface and the back surface coincides with the XY plane, the analysis cartridge (1) comprising at least one chamber (5) capable of containing a liquid intended to be analyzed; - a piezoelectric vibration component (110), which is equipped with a piezoelectric finger (111) extending between two ends, respectively referred to as a first end (111a) and a second end (111b), a hollow cylindrical body (115), the hollow cylindrical body together with the piezoelectric finger (111) forming a piston, i.e., a so-called piezoelectric piston, the piezoelectric finger (111) being partially accommodated in the hollow cylindrical body (115) while being coaxial with the hollow cylindrical body and partially opening outward through an opening in the hollow cylindrical body, and the piezoelectric vibration component also includes a guide cylinder ( 116), wherein the hollow cylindrical body (115) is partially accommodated in a sliding connection, and the piezoelectric vibration component (110) is arranged so that the piezoelectric piston can adopt one or the other of two positions, respectively referred to as an engaged position and a disengaged position, wherein the engaged position is a position in which the second end (111b) is pressed against the support (101) or the back side when the analysis box (1) is placed on the support (101), and the disengaged position is a position in which the second end (111b) is at a certain distance from the back side so as to allow the removal of the analysis box (1) and the support (101); - an engagement component, which is configured to allow the piezoelectric finger (111) to move between one of the engagement position and the disengagement position and the other of the two positions, the engagement component comprising a cam (117) carried by one end of a shaft (118), the shaft (118) being pivotally connected to the guide cylinder and passing through the hollow cylindrical body perpendicularly to the piezoelectric finger, the cam (117) engaging with a through opening (115c) arranged in the side wall of the hollow cylindrical body, so that the piezoelectric piston assumes one or the other of the engagement position and the disengagement position under the sole action of the cam (117), the shaft (118) being advantageously rotationally controlled by means of a motor, in particular a stepping motor.

2. The analysis device (100) according to claim 1, wherein: The cam is capable of taking two angular positions around an axis coinciding with the shaft, referred to as an angular engagement position and an angular disengagement position, respectively, wherein the angular engagement position is the position where the cam applies the engagement position to the piezoelectric piston, and the angular disengagement position is the position where the cam applies the disengagement position to the piezoelectric piston.

3. The analysis device according to claim 2, wherein: The through opening 115c is defined by an inner surface against which the cam 118 can exert a force to impose one or the other of the engaged or disengaged positions on the piezoelectric piston, the through opening advantageously having an elongated shape along the guide of the hollow cylindrical body.

4. The analysis device (100) according to one of claims 1 to 3, wherein: The piezoelectric finger (111) is configured to apply vibration to the back surface once the second end (111b) is pressed against the back surface.

5. The analysis device (100) according to one of claims 1 to 4, wherein: The piezoelectric fingers (111) are configured to apply a bearing force perpendicular to the XY plane against the back surface when in their engaged position.

6. The analysis device (100) according to one of claims 1 to 5, wherein: The analytical device (100) comprises a supplementary magnetic component for applying a supplementary magnetic field in the at least one chamber (5) of the analytical cartridge (1).

7. The analysis device (100) according to one of claims 1 to 6, wherein: The analysis device (100) also comprises means for analyzing the liquid that may be present in the at least one chamber (5).

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

9. The analysis device (100) according to one of claims 1 to 8, wherein: The support (101) is perforated so that when the analysis cartridge (1) rests with its back side on the support (101), the back side of the cartridge is accessible via the second end (111b).

10. The analysis device (100) according to one of claims 1 to 9, wherein: The device includes a loading part, which is engaged with the support (101) and is configured to apply one or the other of an analysis position and a loading position to the support (101), wherein the loading position is a position allowing the analysis box (1) to be positioned and / or removed from the support (101), and the analysis position is a position allowing the piezoelectric finger (111) to engage against the back side of the analysis box (1), and advantageously, the loading part includes a worm gear.

11. The 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 component.

12. The analysis device (100) according to one of claims 1 to 11, wherein: The piezoelectric vibrating component comprises a suspension mechanism which is configured to apply a predetermined contact force to the back side once the piezoelectric finger (111) is in its engaged position. Advantageously, the suspension mechanism comprises a compression-mounted spring (119) which presses against the hollow cylindrical body (115) on the one hand and against the shoulder of the piezoelectric foot on the other hand.

13. The analysis device (100) according to one of claims 1 to 12, wherein: The support member (101) includes a wedge-shaped member configured to force the back surface of the analysis box (1) to coincide with the XY plane.

14. The analysis device (100) according to claim 13, wherein: The analysis device (100) comprises additional components for holding the analysis box (1) on the support (101), and these additional holding components are particularly configured to hold the analysis box (1) at the exhaust port of the box and connect it to the chamber (5), and the additional holding components are also configured to close the exhaust port.

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