Automated multi-sample electrochemical analysis system

Abstract

The invention relates to an automated multi-sample electrochemical analysis system (1) comprising: a sample holder (2) adapted to receive: a plurality of containers (16), each containing an analytical solution; and a first reservoir for a surface reactivation solution; a probe (5) carrying a doped diamond-based working electrode (6) and a counter electrode (7); a controller (8); a robotic platform (9) adapted to be controlled by the controller to perform a relative movement of the probe and the sample holder so as to immerse the electrodes sequentially in the surface reactivation solution and then in the analytical solution of one of the containers. Figure 1

Description

Title of the invention: Automated multi-sample electrochemical analysis system technical field

[0001] The field of the invention is that of chemical analysis in the laboratory, more particularly using doped diamond-based electrodes. Prior art

[0002] Numerous methods exist for chemical analysis in the laboratory. Examples include chromatographic approaches, mass spectrometry, and colorimetric methods. While these methods have proven effective in many analytical fields (health, food processing, industry, environment, etc.), they may not be suitable for analyzing certain specific compounds. These compounds (particularly redox compounds) could be advantageously analyzed using electrochemical methods.

[0003] While electrochemical analysis has been widely reported in the scientific literature for numerous chemical targets, no laboratory analytical device exists that can analyze a multitude of samples automatically. The main reason is that during electrochemical analyses, the electrodes become fouled due to various phenomena (electrodeposition, surface adsorption, biofilm, etc.), which generally leads to drift in measurements of successive samples. There is one exception to this: polarography. This is a specific form of voltammetry that uses a falling-drop mercury electrode as the working electrode. Thus, each measurement is performed on a new drop of mercury, and therefore electrode fouling is no longer a problem. However, this method uses mercury, which has a high degree of toxicity for both humans and the environment.Furthermore, this mercury must be as pure as possible, which requires special processing. Moreover, its implementation is poorly suited to automated multi-sample analysis. Finally, it is limited to analyses where the mercury droplet constitutes a suitable electrode material in terms of potential range, etc. For the rest, even if methods for activating electrodes (e.g., metallic electrodes) exist, such as performing voltammetry cycles in acidic solutions, etc., they are very unreliable in the long term, and generally, the only reliable approach for regenerating the fouled surface is polishing the electrode surface. Such a technique proves prohibitive when it comes to performing repeated and automated amperometric measurements. Description of the invention

[0004] The invention aims to provide an automated multi-sample electrochemical analysis system in which successive sample measurements are not affected by drift problems.

[0005] To this end, the invention proposes an automated multi-sample electrochemical analysis system, comprising: - a sample holder suitable for receiving: • a plurality of containers, each containing an analytical solution; and • a first reservoir for a surface reactivation solution; - an analysis probe carrying electrodes including a working electrode based on doped diamond and a counter electrode; - a controller; - a robotic platform capable of being controlled by the controller to perform a relative movement of the analysis probe and the sample holder so as to immerse the electrodes sequentially in the surface reactivation solution and then in the analysis solution of one of the containers; - an electrochemical measuring instrument coupled to the electrodes and capable of being controlled by the controller so that, when the electrodes are immersed in the analysis solution of one of the containers, it applies an electrochemical measurement protocol to the electrodes and, when the electrodes are immersed in the surface reactivation solution, it applies a surface reactivation protocol to the electrodes.

[0006] Some preferred but not limiting aspects of this system are as follows: - it also includes: • a second reservoir for a reference solution; • a reference electrode immersed in the reference solution; • a salt bridge, one end of which is immersed in the reference solution and the other end of which is connected to the analysis probe in such a way that, when the electrodes of the analysis probe are immersed in the analysis solution of one of the containers, the second end is also immersed in the analysis solution; - it also includes an optical detector and the robotic platform is further capable of being controlled by the controller so that, when the the electrodes of the analysis probe are immersed in the analysis solution of one of the containers, said container is placed in front of the optical detector; - the analysis probe includes a shoulder, the sample holder includes a plate and a plurality of container holders, each container holder including a ring suitable for gripping a container and an elastic element bearing on one side on the ring and on the other side on the plate to move the container from a rest position to an analysis position when the shoulder of the probe comes to rest on the ring; - the robotic platform includes a stage with xy movement suitable for receiving the sample holder and an arm with z movement suitable for receiving the analysis probe; - the arm is also suitable for receiving the second reservoir and the reference electrode; - the first reservoir is capable of receiving a volume of surface reactivation solution at least five times greater than a volume of analysis solution contained in one of the containers. Brief description of the drawings

[0007] Other aspects, objects, advantages and features of the invention will become more apparent upon reading the following detailed description of preferred embodiments thereof, given by way of non-limiting example, and made with reference to the accompanying drawings in which:

[0008] - Fig. 1 is a diagram of an automated multi-electrochemical analysis system samples conforming to a possible embodiment of the invention;

[0009] - Figures 2 and 3 are diagrams representing two possible embodiments of an arrangement of a reference electrode and a second reservoir for a reference solution in the system according to the invention;

[0010] - Figures 4A and 4B are diagrams illustrating a possible embodiment of a automated presentation of an analysis container in front of an optical detector in order to perform electrochemiluminescence measurements.

[0011] DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS

[0012] With reference to [Fig. 1], the invention relates to an automated multi-sample electrochemical analysis system. This system is particularly applicable to the analysis of food samples (e.g., pesticide residues in plant extracts or beverages), the analysis of biological fluids (such as urine, for example, for the detection of nitrites in the diagnosis of urinary tract infections), and the detection of narcotics in saliva. In one possible embodiment, this system can also perform analyses according to methods electrochemiluminescence (ECL), for example, the detection of tryptophan or the measurement of 3-methyindole extracted from pork fat.

[0013] This system 1 comprises a sample holder 2 adapted to receive a plurality of containers, each containing an analytical solution, as well as a first reservoir for a surface reactivation solution. The sample holder 2 takes the form of a tray or a carousel in which container holders 3 are provided (an example of which will be described in connection with Figures 4A and 4B), as well as a receptacle 4 for the first reservoir.

[0014] The sample holder 2 can, for example, accommodate from 10 to 100 container holders. It should be noted that if the sample holder accommodates, for example, 50 container holders, 50 containers will not necessarily be analyzed in each analysis cycle, but as many as necessary, between 1 and 50.

[0015] The containers, which may be in the form of analysis tubes (round, square, or rectangular in cross-section), hold a sufficient volume of liquid to perform an analysis, typically between 10 and 50 mL. Their dimensions are compatible with those of the analysis probe described below and, where applicable, are transparent in the spectral range of interest for ECL analysis, typically between 300 and 700 nm. They are preferably made of glass (Pyrex, quartz, silica, etc.). If the analysis is purely electrochemical, the transparency requirement does not apply, and plastic tubes may be used. In all cases, the tubes must be chemically inert under the conditions of use (no degradation of the tube, for example, in the presence of organic solvent, and no release of chemical pollutants for the analysis).

[0016] The system 1 further comprises an analysis probe 5 carrying electrodes, including a working electrode based on doped diamond 6 (for example, with boron) and a counter electrode 7. The counter electrode 7 is preferably also based on doped diamond. Alternatively, the counter electrode may be made of a noble metal such as gold or platinum, or even be made of stainless steel.

[0017] The analysis probe 5 is made of a chemically inert material, for example Teflon or PEEK. The electrodes 6, 7 are arranged on the probe 5 in such a way that they are electrically insulated from each other and that they can both be brought into contact simultaneously in the analysis solution of one of the containers when the probe is immersed in this solution.

[0018] When doped, for example with boron, synthetic diamond exhibits remarkable electrochemical properties, among which we can mention: i. high chemical stability and high corrosion resistance, allowing operation in harsh environments and / or offering a long service life for such electrodes, ii. a large potential window in aqueous medium (>3V), allowing for example the oxidization or reduction of a wider range of chemical species than with other electrode materials - for the purpose of detecting them, or destroying them in the case of pollution control -, iii. and finally a low double-layer capacitance allowing higher signal-to-noise ratios, for example in the case of amperometric detection of chemical species.

[0019] Synthetic diamond can be produced by chemical vapor deposition via epitaxy in a plasma containing hydrogen and, most often, methane as a carbon source. This diamond can be doped with boron by adding diborane or trimethylbore to the gas phase during growth, for example. Two growth methods are possible: the so-called "hot filament" (HF-CVD) method or the microwave plasma-assisted (MP-CVD) method.

[0020] Polycrystalline diamond is most often preferred for electrochemical applications because it is easier and less expensive to produce than monocrystalline diamond. In particular, it is possible to deposit polycrystalline diamond onto certain substrates over areas of several tens or even hundreds of square centimeters. To achieve this, a substrate is generally seeded with diamond nanoparticles. These diamond particles will grow during the growth phase until they form a continuous film (or coating) on ​​the surface of the substrate.

[0021] An increasing number of chemical analyses are reported in the literature using boron-doped diamond electrodes, due to the aforementioned advantages of such electrodes. Even though these electrodes are known to be relatively less susceptible to fouling than other electrode materials, they nevertheless suffer from the same problem. To overcome this problem, an efficient reactivation method was proposed in patent EP 2 675 941 B1, which allows the diamond electrode surface to be regenerated / reactivated in order to obtain perfectly reproducible results from one measurement to the next. The invention proposes a practical implementation of the reactivation method of patent EP 2 675 941 B1 in the automated multi-sample electrochemical analysis system 1.

[0022] To this end, the sample holder includes, as shown above, a receptacle 4 for a first reservoir of a surface reactivation solution. This first reservoir is capable of receiving a volume of surface reactivation solution at least five times greater than the volume of analytical solution contained in one of the containers. It is thus possible to minimize contamination of the surface reactivation solution by dilution when the analytical probe, previously soaked in an analytical solution, is then immersed in this solution. surface reactivation. The volume of the first reservoir is thus typically between 50 and 500 mL, for example 250 mL.

[0023] The surface reactivation solution preferably consists of the same solvent as the analytical solutions (e.g., water, acetonitrile, etc.). These analytical solutions contain a background salt at a concentration ideally between 0.05 M and 5 M (preferably 1 M). When water is used as the solvent, the background salts are chosen from LiCl₂O₄, Na₂SO₄, NaCl, and KCl. A background salt used in the case of acetonitrile can be tetrabutylammonium hexafluorophosphate or tetrabutylammonium tetrafluoroborate.

[0024] Furthermore, the system 1 includes a controller 8 and a robotic platform 9 capable of being controlled by the controller to perform a relative movement of the analysis probe 5 and the sample holder 2 so as to immerse the electrodes sequentially in the surface reactivation solution and then in the analysis solution of one of the containers.

[0025] The system 1 further comprises an electrochemical measuring instrument 10 (i.e., a potentiostat / galvanostat) coupled to the electrodes and capable of being controlled by the controller 10 to, when the electrodes are immersed in the analysis solution of one of the containers, apply to the electrodes an electrochemical measurement protocol (for example a voltammetric measurement protocol such as a square wave voltammetry protocol) and, when the electrodes are immersed in the surface reactivation solution, apply to the electrodes a surface reactivation protocol such as that described in patent EP 2 675 941 Bl.

[0026] It is thus possible to reactivate the surface of the diamond-based electrode(s) of the analysis probe after a measurement has been taken in one of the containers and before another measurement is taken in another container. The controller can, in particular, be programmed to allow such surface reactivation between each new measurement or series of measurements.

[0027] The invention thus makes possible the automated analysis of multiple samples without drift in the measurements. Furthermore, with the presence, on the sample holder, of the first reservoir for the surface reactivation solution next to the analysis containers and with the use of the same robotic platform to perform the measurements and the surface reactivation, the invention offers ease of implementation of such a surface reactivation protocol, with a reduced impact on the duration of such a protocol between each new measurement or series of measurements. As shown in [Fig. 1], the receptacle 4 for the first reservoir can in particular be arranged in the center of the sample holder 2 so as to generally limit the time of the relative movement of the analysis probe and the sample holder to move the probe from an analysis position where it is immersed in an analysis solution. to a surface reactivation position where it is immersed in the surface reactivation solution, and vice versa. Finally, the volume of the first reservoir is designed to allow multiple surface reactivations without contamination problems.

[0028] In a possible embodiment illustrated in [Fig.1], the robotic platform 9 includes a stage with a displacement in xy suitable for receiving the sample holder 2 and an arm with a displacement in z suitable for receiving the analysis probe 5.

[0029] With reference to [Fig. 2] and 3, the system further comprises a second reservoir 11 for a reference solution, and a reference electrode 12 immersed in the reference solution so as to isolate it from the analytical solution to prevent any possibility of contamination. Like the working electrode 6 and the counter electrode 7, the reference electrode 12 is connected to the electrochemical measuring instrument 10. The system also comprises a salt bridge 13a, 13b, one end of which is immersed in the reference solution and the other end of which is connected to the analytical probe 5 such that, when the electrodes of the analytical probe are immersed in the analytical solution of one of the containers, the other end is also immersed in the analytical solution. The salt bridge thus ensures ionic conductivity between the analytical solution and the reference solution.

[0030] The salt bridge 13a, 13b can be in the form of a flexible tube made of an inert material (for example, PTFE or PFA) filled with a salt-charged gel. The reference electrode can be a calomel electrode or AgIAgCl. The reference solution is typically a saline solution, preferably based on KCl (with a concentration between 0.5 M and saturation, for example, 3 M).

[0031] In a first possible embodiment illustrated in [Fig. 2], the second reservoir 11 is fixed relative to the analysis probe 5, in order to facilitate the connection between the reference solution and the analysis solution via the salt bridge and to avoid any potential mobility problems with the tube constituting the salt bridge 13a. For example, the z-moving arm can also accommodate the second reservoir 11 and the reference electrode 12. The second reservoir 11 thus moves at the same time as the analysis probe, for example, by being fixed and positioned directly above the analysis probe 5. In this embodiment, the salt bridge can consist of a Teflon tube 20 cm long with an internal diameter of 2 mm (external diameter of 4 mm), filled with an agar-agar gel loaded with a saturated KCl solution.

[0032] In a second possible embodiment illustrated in [Fig. 3], the second reservoir is fixed and stationary relative to the sample holder, while the analysis probe and the sample holder can be driven in relative motion (the probe being able, in the example illustrated in [Fig. 1], to be driven along the z-axis). In this case, only The salt bridge is mobile, which considerably reduces the bulk of the analysis probe, which no longer has to carry the second reservoir and the reference electrode.

[0033] In an alternative embodiment of the analysis system according to the invention, it is also configured to allow for electrochemilium inescence (ECL) measurements. To this end, with reference to [Fig. 1], the system 1 also includes an optical detector 14 capable of detecting the photons emitted during ECL reactions, and the robotic platform is adapted to be controlled by the controller so that, when the electrodes 6, 7 of the analysis probe 5 are immersed in the analysis solution of one of the containers, said container is placed in front of the optical detector 14. In this way, during an ECL measurement, the analysis probe immersed in the analysis solution is automatically brought in front of the optical detector.

[0034] The optical detector 14 can be a photomultiplier tube, a SiPM diode, or a cooled avalanche diode. Alternatively, the optical detector can take the form of a diode array allowing the recording of an overall emission spectrum.

[0035] The optical detector 14 can be arranged below the sample holder and housed in a casing having on its upper face an opening allowing the introduction of a lower part of the container being measured.

[0036] For example, with reference to Figures 4A and 4B, the sample holder 2 comprises a plate with container receiving ports. The sample holder accommodates a plurality of container holders, each comprising a ring 15 adapted to be inserted into one of the ports and to clamp a container 16 inserted into the port. Each container holder also comprises an elastic element 17, such as a compression spring, bearing on the ring 15 on one side and on the plate on the other. The analysis probe 5 comprises a shoulder 18 adapted to bear against the ring 15 when the probe is immersed in the container 17, allowing the container to be moved from a rest position ([Fig. 4A]) to an analysis position ([Fig. 4B]) where a lower portion of the container protrudes from the plate and can thus be presented to the optical detector 14.Removing the analysis probe from the container allows, through the effect of a decompression of the elastic element of the spring 17, the container to automatically return to its rest position.

[0037] To eliminate background interference that could interfere with the ECL measurement, the analysis system 1 may include an enclosure that places the sample being analyzed in absolute darkness. This enclosure notably encloses the sample holder, the analysis probe, and the optical detector.

Claims

Demands

1. An automated multi-sample electrochemical analysis system (1), comprising: - a sample holder (2) capable of receiving: • a plurality of containers (16) each containing an analytical solution; and • a first reservoir for a surface reactivation solution; - an analytical probe (5) carrying electrodes including a doped diamond-based working electrode (6) and a counter electrode (7); - a controller (8); - a robotic platform (9) capable of being controlled by the controller to perform a relative movement of the analytical probe and the sample holder so as to immerse the electrodes sequentially in the surface reactivation solution and then in the analytical solution of one of the containers;- an electrochemical measuring instrument (10) coupled to the electrodes and capable of being controlled by the controller so that, when the electrodes are immersed in the analysis solution of one of the containers, it applies an electrochemical measurement protocol to the electrodes and, when the electrodes are immersed in the surface reactivation solution, it applies a surface reactivation protocol to the electrodes.

2. A system according to claim 1, further comprising: - a second reservoir (11) for a reference solution; - a reference electrode (12) immersed in the reference solution; - a salt bridge (13a, 13b) having one end immersed in the reference solution and a second end connected to the analysis probe such that, when the electrodes of the analysis probe are immersed in the analysis solution of one of the of the containers, the second end is also immersed in the analysis solution.

3. System according to any one of claims 1 and 2, further comprising an optical detector (14) and wherein the robotic platform is capable of being controlled by the controller so that, when the electrodes of the analysis probe are immersed in the analysis solution of one of the containers, said container is placed in front of the optical detector.

4. System according to claim 3, wherein the analysis probe includes a shoulder (18), the sample holder includes a plate and a plurality of container holders, each container holder including a ring (15) adapted to enclose a container (16) and an elastic element (17) bearing on the ring on one side and on the plate on the other to move the container from a rest position to an analysis position when the shoulder of the probe comes to rest on the ring.

5. System according to any one of claims 1 to 4, wherein the robotic platform includes a stage with an xy displacement suitable for receiving the sample holder and an arm with a z displacement suitable for receiving the analysis probe.

6. System according to claim 5 in combination with claim 2, wherein the arm is also suitable for receiving the second reservoir (11) and the reference electrode (12).

7. System according to any one of claims 1 to 6, wherein the first reservoir is capable of receiving a volume of surface reactivation solution at least five times greater than a volume of analysis solution contained in one of the containers.

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