Mechanical resonator intended for use in a system for measuring a property of a particle

Abstract

The invention relates to a mechanical resonator (R) for use in a system for measuring a property of a particle, comprising: A body (1) having an oscillating part (10) capable of vibrating relative to anchoring means along a transverse plane and a fluidic channel (103) integrated into its oscillating part (10) and through which a fluid containing said particle is circulated, characterized in that it comprises: A hinge mechanism created between the oscillating part (10) and the anchoring means, A strain gauge (3), of the suspended type, configured to measure the deformation of the oscillating part (10) during its vibration. Figure to be published with the abbreviation: Figure 2

Description

Title of the invention: Mechanical resonator for use in a system for measuring a property of a particle. Technical field of the invention

[0001] The present invention relates to a mechanical resonator intended to be used in a system for measuring a property of a particle and in a corresponding system. State of the art

[0002] To detect the presence of biomarkers of interest such as proteins, exosomes, circulating RNA, circulating DNA, viruses, or larger target species such as bacteria and cells, it is known to use biosensors.

[0003] Among biosensors, there is notably the category of gravimetric sensors. These are based on the use of a mechanical oscillator or resonator, equipped with an oscillating part comprising a suspended beam or plate set into vibration according to one of its resonance modes. Any target that attaches to the surface of the resonator causes an increase in its mass, which decreases the resonance frequency by an offset related to the mass of the captured target.

[0004] By continuously measuring the resonance frequency fluctuations, it is then possible to trace back to the mass adsorbed on the resonator in real time and, for example, to follow adsorption kinetics with targets.

[0005] A solution proposed in the prior art consists of integrating and delimiting a fluidic channel within the resonator itself, while the latter oscillates in a fluid-free cavity. The advantage lies in a quality factor that is minimally affected, even in the presence of fluid circulating in the oscillator, and thus in an optimized detection limit. This type of resonator is commonly called an SMR ("Suspended MicroChannel Resonator") or an SNR ("Suspended Nanochannel Resonator"), depending on the dimensions of its fluidic channel. It should be noted that a resonator with a fluidic channel whose width or thickness is less than Ipm will be referred to as an SNR; otherwise, it will be an SMR.

[0006] By applying a pressure gradient between a fluidic inlet and outlet of the circuit, it is possible to control the fluid flow (its flow rate and direction), and therefore the passage of suspended particles through the SMR (or SNR). This type of sensor has been used for various applications, including the individual weighing of biological particles such as cells, bacteria, nanoparticles, or the detection of specific proteins by pre-functionalizing the internal walls of the SMR. This operating principle is now well known. Patent application US2021 / 046477A1 and patents US8899102B1, US8631685B2 and US8312763B2 describe this type of sensor.

[0007] Documents US2021 / 046477A1 and US8899102B2 describe, for their part, classic SMR type solutions.

[0008] In these prior solutions, the measurement of the deformation of the suspended beam can be carried out by different means: - Capacitive, - Optics, - Piezoresistive.

[0009] Measurement by piezoresistive means offers numerous advantages. The gauges are inexpensive, easy to install, and they allow for multichannel reading.

[0010] Conventionally, the gauge is implanted directly into the upper membrane of the resonator body by doping (localized doping by ion implantation). It thus follows the deformation of the oscillating part during its vibration.

[0011] It has been observed that in existing structures (See referenced publication Suspended Nanochannel Resonator Arrays with Piezoresistive Sensors for High-Throughput Weighing of Nanoparticles in Solution - Marco Gagino, Georgios Katsikis, Selim Olcum, Léopold Virot, Martine Cochet, Aurélie Thuaire, Scott R. Manalis, and Vincent Agache - ACS Sensors 2020 5 (4), 1230-1238 - DO1:10.1021 / acssensors.0c00394), where the gauge is directly embedded, electrical reading limits the device's performance. In other words, the signal-to-noise ratio is too low and, in particular, lower than that obtained by comparison via optical reading (for example, by illuminating a photodiode with a laser reflected off the oscillating SNR).This can be explained by the low amplitude of the piezoresistive signal (resistance variation) due to the chosen configuration (ion implantation in the upper membrane of the resonator over a very thin layer compared to the total thickness of the resonator body, which deforms). Furthermore, we observed a degradation of the signal-to-noise ratio related to the conductivity level of the fluid circulating in the resonator channel, due to insufficient isolation from the piezoresistivity confined within the upper membrane of the resonator.

[0012] There is therefore a need to obtain an SMR or SNR type resonator using a piezoresistivity measurement and in which a maximum of the energy linked to the deformation of the oscillating part of the resonator is concentrated on the strain gauge, thus increasing the amplitude of the signal and therefore improving the signal / noise ratio. Description of the invention

[0013] This objective is achieved by a mechanical resonator intended for use in a system for measuring a property of a particle, comprising: - A body comprising an oscillating part capable of vibrating relative to anchoring means along a transverse plane and a fluidic channel integrated into its oscillating part and in which a fluid containing said particle is made to circulate, - A hinge mechanism created between the oscillating part and the anchoring means, - A strain gauge, of the suspended type, configured to measure the deformation of the oscillating part during its vibration.

[0014] According to one particular feature, the oscillating part comprises a suspended beam extending cantilevered along a longitudinal axis and two lateral beams supporting said suspended beam, said fluidic channel being provided through said lateral beams and the suspended beam.

[0015] According to another feature, the hinge mechanism comprises: - At least one first mechanical and electrical connecting element forming a first gateway joining the oscillating part to a first anchoring part of the anchoring means, this first connecting element being deformable in bending, - Torsion blades formed by the lateral walls of the fluidic channel in each lateral beam.

[0016] According to another feature, the strain gauge is arranged to form a second suspended walkway between a second anchoring part of the anchoring means and the oscillating part.

[0017] According to another feature, the first gateway and the second gateway are made along two distinct parallel planes, perpendicular to the transverse plane of vibration of the oscillating part.

[0018] According to another feature, the resonator comprises: - An electrical circuit formed between a first electrical contact zone and a second electrical contact zone, between which an electrical signal is intended to be measured, - The first electrical contact zone being located on the first anchoring section, - The second electrical contact zone being located on the second anchoring part, - The electrical circuit being arranged between the first electrical contact zone and the second electrical contact zone, via the first junction element, the oscillating part and the strain gauge.

[0019] According to another feature, the resonator includes a second mechanical and electrical connecting element, arranged symmetrically to the first connecting element with respect to the longitudinal axis and forming a third bridge joining the oscillating part to a third anchoring part, this second connecting element also being deformable in bending to contribute to forming said hinge mechanism for the vibration movement of the oscillating part.

[0020] According to another feature, the first anchoring part and the third anchoring part are part of the body of the mechanical resonator.

[0021] According to another feature, the body has two gaps made on either side of the longitudinal axis, hollowed out over its entire thickness, each gap being formed so as to leave respectively the first mechanical joining element and said second joining element between the oscillating part and their respective anchoring part.

[0022] According to another feature, the body of the resonator is made by an assembly of several superimposed layers.

[0023] According to another feature, each electrical contact area is made by metallization on a layer of the resonator body.

[0024] The invention relates to a system for measuring a property of a particle comprising: - A mechanical resonator comprising an oscillating part, - Excitation means configured to vibrate the oscillating part at an excitation frequency, - Means of measuring an electrical signal at the output of the mechanical resonator, - The mechanical resonator being as defined above.

[0025] According to one particular feature, the excitation means comprise a piezoceramic on which the mechanical resonator rests. Brief description of the figures

[0026] Other features and advantages will appear in the detailed description that follows, made in conjunction with the figures listed below: - Fig. 1 represents a diagram illustrating the principle of implementation of the measurement system of the invention; - Fig. 2 represents, seen in perspective, the mechanical resonator used in the system of the invention, according to an advantageous embodiment; - Fig. 3 represents, seen from above, the mechanical resonator of Fig. 2; - Figure [Fig. 4] represents a longitudinal cross-sectional view along Cl of the resonator mechanics of the [Fig.3];

[0027] Detailed description of at least one embodiment

[0028] The invention relates in particular to a system used for measuring at least one property (for example, mass, volume, density) of a particle. A particle is understood to mean, for example, a biological particle such as a cell, exosome, virus, bacterium, etc. A particle is also understood to mean an inorganic particle such as, for example, a particle of gold, polystyrene, etc.

[0029] For the remainder of the description, an orthonormal coordinate system (X, Y, Z) is defined, with the plane (X, Y) being defined as a horizontal plane.

[0030] With reference to Figures 1 to 4, the measurement system comprises a mechanical resonator (referenced as R in the accompanying figures), more commonly known as an SMR ("Suspended MicroChannel Resonator" - hereafter also referred to as an SMR) or an SNR ("Suspended Nanochannel Resonator"), its micro or nano nature depending in particular on the dimensions of its integrated fluidic channel. A resonator with a fluidic channel whose width or thickness is less than Ipm will be referenced as an SNR; otherwise, it will be an SMR.

[0031] In the context of the invention, the resonator R comprises a body 1.

[0032] The body 1 comprises an oscillating part 10. The oscillating part 10 comprises a A suspended beam 100 extends cantilevered along a longitudinal axis (along X), and two lateral beams 101 and 102 support said suspended beam. The two lateral beams 101 and 102 and the suspended beam 100 are arranged to form a T.

[0033] The oscillating part 10 includes an integrated fluidic channel 103, beginning with a fluidic inlet, then extending inside the first lateral beam 101 by a first lateral section, continuing inside the suspended beam 100 by a forward section, going from its first lateral section to the free end of the suspended beam 100 and by a return section going from the free end of the suspended beam 100 to a second lateral section, the fluidic channel ending on a fluidic outlet, via the second lateral section located through the second lateral beam 102.

[0034] The fluidic channel 103 is formed by sealed walls on all four sides (top, bottom, and sides) and is intended for use in injecting a fluid containing one or more particles to be characterized. The lateral beams 101, 102, and the suspended beam 100 of the oscillating part 10 are therefore hollow to allow the fluid to circulate.

[0035] A mechanical resonator R of the SMR type allows larger particle sizes (than an SNR) to circulate in its fluidic channel 103, and to potentially analyze more complex samples (in terms of heterogeneity in size of suspended particles).

[0036] The system includes excitation means 2 configured to vibrate the oscillating part 10 of the resonator R, and more particularly its suspended beam 100, at an excitation frequency F_smr. This excitation frequency is advantageously the frequency of a resonance mode of the resonator.

[0037] In this type of resonator R, the vibration is generally carried out of plane (as indicated by the curved arrow in [Fig. 1]). The out-of-plane vibration is carried out along the (Z) direction.

[0038] The oscillating part 10 is capable of being set into vibration to oscillate at the excitation frequency F_smr, this frequency advantageously being the resonance frequency at its fundamental natural mode or one of its higher natural modes, or even a combination of these modes.

[0039] As a reminder, such a mechanical resonator R can be excited according to several modes of vibration. For each mode of vibration, the resonator has vibration nodes and antinodes of vibration.

[0040] As a reminder, a vibration antinode corresponds to an area of ​​the suspended part where the vibration amplitude is maximum for the vibration mode used.

[0041] By applying a pressure gradient between the upstream and downstream ports of the fluidic channel 103 integrated into the resonator R, it is possible to control the fluid flow (its flow rate and direction) in the fluidic channel 103, and therefore the passage of suspended particles through the fluidic channel of the mechanical resonator 1. When a particle flows through the fluidic channel of the resonator, it transiently alters the mass (of Am) of the suspended beam 100 of the resonator R, resulting in a shift in its (resonance) frequency that is proportional to the floating mass of the particle. The floating mass of the particle is defined as the difference in mass between the particle and the mass of the carrier fluid for a given volume; if the particle has the same density as the carrier fluid, there is no difference in mass and the floating mass is zero.

[0042] The frequency shift AF_smr ([Fig. 1]) of the resonator R depends in fact on the added mass Am, the total mass m of the resonator, and a correction coefficient a which depends specifically on the position of the added particle P and the resonance mode of the resonator (for example, in bending) according to the following relation:

[0043] _ km Fsmr “ ' m

[0044] Thus, when a particle of given floating mass Am is injected into the fluidic channel 103 of the resonator R, a maximum vibration amplitude is obtained when this particle is located at the level of the antinode of vibration (for the mode of vibration M_1 for example) and therefore a maximum frequency shift. Note that, depending on the difference in density between the particle and the carrier fluid, the floating mass Am will be positive (in the case of a denser particle) or negative (in the case of a less dense particle).

[0045] The actuation / excitation of the oscillating part 10 of the resonator R is advantageously achieved by bringing a piezoelectric ceramic into contact with the rear face of the device to actuate the SMR resonator and its oscillating part 10, this piezoelectric ceramic playing the role of the aforementioned excitation means 2. The piezoelectric ceramic is, for example, bonded to a printed circuit board, itself designed to apply an electrical potential that will deform the piezoelectric material. The vibration of the latter is achieved by applying, for example, an electrical signal at the resonant frequency of the resonator. It should be noted that the applied signal can collectively actuate several oscillating parts (several SMRs and / or several SNRs) arranged in parallel on the same component and the different resonance modes desired for each of them. In this latter case, the actuation signal applied to the piezoelectric ceramic comprises several frequencies.

[0046] The reading is performed using a strain gauge 3 operating by piezoresistive effect. The gauge 3 is configured to convert mechanical force into an electrical signal. The greater the compression of the gauge, the lower its electrical resistance. This is achieved by inserting the gauge 3 into an electrical circuit (for example, a Wheatstone bridge), the deformation of the gauge defining the electrical resistance of the circuit.

[0047] The principle of the invention is illustrated schematically by [Fig. 1]. It consists of proposing a mechanical arrangement adapted to the level of the resonator R to direct a maximum of the energy of the deformation of the oscillating part 10 and its suspended beam 100 towards the strain gauge 3. In other words, it is desired that the mechanical deformation of the oscillating part 10 of the resonator R, during its vibration, be concentrated as much as possible on the strain gauge 3.

[0048] To this end, the invention consists of providing: - At least one first part, called anchoring 4a, and a second part, called anchoring 5, separated from each other, without electrical connection between these two parts. These two anchoring parts are mechanically connected to each other via the frame 7 ([Fig.1] - the frame is chosen to be electrically insulating). - A hinge mechanism between the swinging part and the anchoring parts. This hinge mechanism is formed by: • Creating a first mechanical and electrical junction element 104a, deformable in bending, this first junction element 104a forming a first gateway between the oscillating part 10 and the first anchoring part 4a, • Using torsion blades made by the lateral walls of the fluidic channel in the lateral beams 101 and 102 of the oscillating part 10.

[0049] According to a particular aspect of the invention, the strain gauge 3 is arranged to form a second suspended walkway between the oscillating part 10 and the fixed part 5.

[0050] According to a particular embodiment, a first electrical contact zone 40 and a second electrical contact zone 50 are created, between which an electrical signal M is read, taking into account the resistance in the electrical circuit. The first electrical contact zone 40 is advantageously located on the first anchoring portion 4a and the second electrical contact zone 50 is advantageously located on the second anchoring portion 5.

[0051] The electrical circuit is made between the first electrical contact zone 40 and the second electrical contact zone 50, via the first anchoring part 4a, the first connecting element 104a and / or the side beam 101, the oscillating part 10 of the resonator R, the strain gauge 3 and the second anchoring part 5. Depending on the deformation undergone by the strain gauge 3, the resistance will be more or less high and the measured electrical signal M will vary.

[0052] The junction of the oscillating part 10 with the first anchoring part 4a, via the first junction element 104a, and the junction of the oscillating part 10 with the second anchoring part 5, via the strain gauge 3, are made along two planes PI, P2 ([Fig.4]) parallel to each other, along (X, Y), these two planes extending for example respectively along the upper face of the body 1 of the resonator R and along the lower face of the body of the resonator R.

[0053] The hinge mechanism is created at the level of the mechanical resonator R with a connecting element 104a which, due to its limited thickness (for example, on the order of one hundred µm, with a thickness ratio between 10 and 100, between the thickness of the beam and that of the connecting element), is very flexible in bending (and very stiff in compression, notably much stiffer in compression than the strain gauge 3). The flexibility in bending created by the hinge mechanism results in low energy losses during the vibration of the resonator. The deformation is mainly absorbed by the strain gauge. And since the strain gauge 3 is suspended, a maximum of the deformation energy is transmitted to the strain gauge 3. Thus, it is the strain gauge that absorbs the majority of the deformation of the oscillating part 10.

[0054] Advantageously, the strain gauge has an elongated shape and a reduced cross-section, which gives it greater mechanical strength, increased resistance to stress at constant force and resistance to buckling.

[0055] According to the embodiment shown in Figures 2 to 4, the body 1 of the resonator R comprises the first anchoring part 4a and also a third anchoring part, referenced 4b because it is advantageously identical to the first anchoring part 4a described above. This third anchoring part 4b is also mechanically connected to the frame 7.

[0056] The oscillating part 10 of the resonator R is connected to this third anchoring part 4b by a second mechanical and electrical junction element 104b, forming a second gateway, symmetrical to the first gateway.

[0057] The two connecting elements 104a, 104b contribute to fulfilling the hinge function 6 between the oscillating part 10 and the two anchoring parts 4a, 4b, each in combination with the torsion blades formed by the lateral walls of the fluidic channel 103 in each lateral beam 101, 102. The two connecting elements 104a, 104b are identical and contribute to the hinge mechanism by being chosen to be very flexible in bending and very stiff in compression, stiffer in compression than the strain gauge 3, so as to transmit a maximum of the deformation energy from the oscillating part 10 to the strain gauge 3.

[0058] According to a particular aspect of the invention, to create the first connecting element 104a and the second connecting element 104b, two distinct gaps 105a, 105b are cut into the body 1 of the resonator R between each anchoring part 4a, 4b and the oscillating part 10. This gives two different gaps 105a, 105b, made symmetrically on either side of the longitudinal axis (along X). Each gap 105a, 105b is made so as to leave, between the anchoring part 4a, 4b and the oscillating part 10, the said joining element 104a, 104b, over a determined thickness, less than the thickness E of the layers ([Fig.4]) forming mainly the body 1 of the resonator R. The gaps are also created to form the lateral beams 101, 102 of the oscillating part 10, and thus to help in the formation of the hinge mechanism.

[0059] Advantageously, the junction of the oscillating part 10 with each anchoring part 4a, 4b, via each junction element 104a, 104b, and the junction of the oscillating part 10 with the fixed part 5, via the strain gauge 3, are made along the two parallel planes PI, P2 mentioned above, extending for example respectively along the upper face of the body 1 of the resonator R and along the lower face of the body 1 of the resonator ([Fig.4]).

[0060] Thus, during the vibration of the oscillating part, it is caused to flex at each connecting element 104a, 104b, contributing to the hinge mechanism, along with the torsion blades mentioned above. The deformation The signal is transmitted to the strain gauge 3 with a high signal-to-noise ratio, as the strain gauge is suspended between the oscillating part 10 of the resonator R and the fixed part 5, the fixed part 5 being separate. In other words, a maximum of the mechanical deformation is thus transmitted to the strain gauge 3, resulting in a strong signal and therefore improving the final signal-to-noise ratio by masking noise.

[0061] The electrical circuit formed between the two electrical contact zones 40, 50 is advantageously created by uniform high doping throughout the structure. The electrical circuit is created by etching the silicon and mechanically cutting the paths. Thus, depending on the level of deformation applied to the oscillating part 10, the resistance of the circuit passing through the strain gauge 3 will be greater or lesser.

[0062] As indicated above, the oscillating part 10 is fixed to the first anchoring part 4a and the third anchoring part 4b, via its two lateral beams 101, 102. Thus, during its deformation, its lateral beams 101, 102 are subjected to torsional deformation. These lateral beams 101, 102 are therefore chosen to be torsionally flexible.

[0063] By way of non-limitation, the body of the mechanical resonator R is advantageously made by an assembly of several doped layers.

[0064] Electrical contact zones can be formed by metallization on the fixed part and the first anchoring part.

[0065] The manufacturing process for the device uses conventional MEMS / NEMS manufacturing technologies, by working on superimposed layers: - Photolithography of a NEMS layer present on a SOI substrate ("Silicon on insulator") to form strain gauge 3, - Deposition of a protective oxide on the NEMS layer, - Photolithography of the protective oxide layer above strain gauge 3 and fluidic channel 103, - Epitaxy of a thick MEMS layer of silicon (e.g., 20 pm), - Deep photolithography of the silicon MEMS layer to form the fluidic channel 103 and an opening intended to form each mechanical junction element 104a, 104b, - Bonding of a thin layer (for example, an SOI wafer and 500nm) to close the fluidic channel 103 from above, - Deep photolithography of the MEMS layer to outline the oscillating part 10, the fixed part 5 and engraving of the edges of each junction element 104a, 104b, - Isotopic chemical etching of the protective oxide layer to release the oscillating part 10, Metallization to create electrical contact zones 40, 50.

Claims

Demands

1. Mechanical resonator (R) intended for use in a system for measuring a property of a particle, comprising: - A body (1) having an oscillating part (10) capable of vibrating relative to anchoring means along a transverse plane and a fluidic channel (103) integrated in its oscillating part (10) and in which a fluid containing said particle is made to circulate, - Characterized in that it comprises: - A hinge mechanism created between the oscillating part (10) and the anchoring means, - A strain gauge (3), of the suspended type, configured to measure the deformation of the oscillating part (10) during its vibration.

2. Resonator according to claim 1, characterized in that the oscillating part comprises a suspended beam (100) extending cantilevered along a longitudinal axis and two lateral beams (101, 102) holding said suspended beam (100), said fluidic channel (103) being provided through said lateral beams and the suspended beam.

3. Resonator according to claim 2, characterized in that the hinge mechanism comprises: - At least one first mechanical and electrical connecting element (104a) forming a first bridge joining the oscillating part (10) to a first anchoring part (4a) of the anchoring means, this first connecting element (104a) being deformable in bending, - Torsion blades formed by lateral walls of the fluidic channel (103) in each lateral beam (101, 102).

4. Resonator according to claim 3, characterized in that the strain gauge (3) is arranged to form a second suspended gateway between a second anchoring part (5) of the anchoring means and the oscillating part (10).

5. Resonator according to claim 4, characterized in that: - The first and second gateways are made along two distinct parallel planes, perpendicular to the transverse plane of vibration of the oscillating part (10).

6. Resonator according to claim 5, characterized in that it comprises a second mechanical and electrical connecting element (104b), arranged symmetrically to the first connecting element (104a) with respect to the longitudinal axis and forming a third bridge joining the oscillating part (10) to a third anchoring part (4b), this second connecting element (104b) also being deformable in bending to contribute to forming said hinge mechanism for the vibration movement of the oscillating part (10).

7. Resonator according to claim 6, characterized in that the first anchoring part (4a) and the third anchoring part (4b) are part of the body (1) of the mechanical resonator (R).

8. Resonator according to claim 7, characterized in that the body has two gaps made on either side of the longitudinal axis, hollowed out over its entire thickness, each gap being formed so as to leave respectively the first mechanical joining element (104a) and said second joining element between the oscillating part (10) and their respective anchoring part.

9. Resonator according to any one of claims 1 to 8, characterized in that it comprises: - An electrical circuit formed between a first electrical contact zone (40) and a second electrical contact zone (50), between which an electrical signal (M) is intended to be measured, - The first electrical contact zone (40) being located on the first anchoring part (4a), - The second electrical contact zone (50) being located on the second anchoring part (5), - The electrical circuit being arranged between the first electrical contact zone (40) and the second electrical contact zone (50), via the first junction element (104a), the oscillating part (10) and the strain gauge (3).

10. Resonator according to claim 9, characterized in that the body of the resonator is made by an assembly of several superimposed layers.

11. Resonator according to claim 10, characterized in that each electrical contact zone is made by metallization on a layer of the resonator body.

12. A system for measuring a property of a particle comprising: - A mechanical resonator (R) including an oscillating part (10), - Excitation means (2) configured to vibrate the oscillating part (10) at an excitation frequency (F_smr), - Means for measuring an electrical signal (M) at the output of the mechanical resonator (R), - Characterized in that the mechanical resonator (R) is as defined in any one of claims 1 to 11.

13. System according to claim 12, characterized in that the excitation means comprise a piezoceramic on which the mechanical resonator rests.

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