ES2366516B1 - PROCEDURE FOR COATING ELECTRODES OF AN ELECTRONIC DEVICE BY MAGNETIC ATTACKING, ELECTRODE SO OBTAINED, DEVICE THAT INCORPORATES SUCH ELECTRODE AND USE OF SUCH DEVICE. - Google Patents

Abstract

Electrode coating procedure of an electronic device by magnetic entrapment, electrode thus obtained, device incorporating said electrode and use of said device. # A procedure for producing coatings on one of the electrodes, called working electrode, of electronic devices is described. intended for the realization of amplified electrochemical measurements, and that once the measurement has been carried out, the coating can be detached by returning the electronic device to its previous state to the coating; It can be reused for other measurements, using the same or another coating.

Description

Electrode coating procedure of an electronic device by magnetic entrapment, electrode thus obtained, device incorporating said electrode and use of said device.

Object of the invention

The present invention pertains to the field of microelectronic devices and the specific electrode coatings of said microelectronic devices.

A first object of the present invention is a microelectronic device in which at least one electrode has been modified with a removable coating by magnetic entrapment.

A second object of the invention consists in a process for performing removable coatings on electrodes of microelectronic devices by magnetic entrapment.

Background of the invention

Since its discovery, carbon nanotubes (NTC) have become one of the most promising nanomaterials and both the production process and its purification, modification and / or functionalization have been extensively subjected to industrial protection. Apart from many other potential applications, NTCs have been exploited in a significant number of electroanalytical and sensor applications. This is mainly due to the fact that the incorporation of NTC to the different types of electrodes allows to take advantage of the high mechanical resistance of this nanocomponent, which also shows great chemical stability and electronic conductivity. NTC-modified electrodes also have active surfaces of greater roughness and surface, lower levels of nonspecific adsorption of biocomponents, significant levels of electrocatalytic activity to a wide variety of molecules, and greater electron transfer efficiency than similar unmodified electrodes.

The simplest strategy for the production of electrodes modified with NTC is to deposit a small volume of a dispersion of NTC (usually prepared in organic solvents) on the surface of the electrode, followed by evaporation of the solvent. However, a number of alternative strategies have been described to date, based among others on electrodeposition, electrophoresis, stamping, spin-coating, entrapment, chemical / covalent conjugation and self-assembly of alternate layers (Layer-by-layer formation) of the NTC. In part of the existing works, the NTCs are incorporated into the electrode surface in combination with biopolymers, mineral oils, conductive polymers and / or nanoparticles, shaping a variety of composite materials that significantly improve the electrochemical performance of the electrode.

However, these procedures generally involve production strategies of at least hours and are rarely compatible with the easy regeneration of the electrode by removing the NTCs. A single report (a US patent application US 2005/0239948 A1 and the corresponding articles Haik, Y .; Chatterjee, J .; Chen, CJ Nsti Nanotech 2004, Vol 3, Technical Proceedings 2004, 300-301 and Haik, Y. ; Chatterjee, J .; Chen, CJ In Nsti Nanotech 2004, Vol 3, Technical Proceedings: US, 2005; Vol. US 2005/0239948 A1) describes the combined use of NTC and magnetic nanoparticles. It describes the nonspecific adsorption of magnetic nanoparticles (5-100 nm) on the surface of the NTC, suspension in a matrix (polymeric, ceramic, metallic, a gel), alignment by a magnetic field, and solidification of the compound by drying / removal of the matrix. The resulting material is then cut into sheets, without specifying any potential application.

The incorporation of carbon nanotubes (NTC) to the electrode surface contributes to increase its roughness and surface area, reduces the level of nonspecific adsorption of biocomponents, provides electrocatalytic activity against a variety of molecules, and improves electron transfer. To date, this type of modification is based on the irreversible deposition of NTCs on the surface through strategies that are poorly compatible with electrode reuse, often using organic solvents potentially harmful to the operator and the environment. In addition, since NTCs are a highly porous material, electrodes modified with NTC may suffer from unspecific adsorption levels and / or electrodeposition of biomolecules that are too high to guarantee the absence of cross contamination between samples under study and the specificity and reproducibility of the measurement protocol.

The deposition of NTC dispersed in organic solvents has in some cases detrimental effects on the integrity of the electrodes, for example the dissolution of the pastes / inks with which the screen-printed electrodes (SPE) are produced and the reduction of the average life time of the same.

Description of the invention

The process object of the invention describes an extremely fast and simple method for the reversible production of electronic or microelectronic devices modified with carbon nanotube (NTC) coatings by magnetic entrapment in aqueous medium.

This procedure exploits the strong tendency shown by NTCs to adsorb unspecifically on the surface of magnetic particles (PM), for example PM that have been previously coated with protein. PM / NTC assemblies are subsequently captured on the surface of an electronic or microelectronic device by magnetic capture, a procedure that is extremely fast and simple. Devices modified in this way have electrocatalytic behavior against a variety of analytes, better detection limits and significantly higher signals than unmodified electrodes. After taking measurements, and in the absence of magnetic attraction, the PM / NTC can be easily removed by washing and the surface of the device can be reused indefinitely.

Carbon nanotubes (NTC) have been exploited for a significant number of electroanalytical and sensor applications. Its incorporation into the electrode surface contributes to increase its roughness and surface area, reduces the level of nonspecific adsorption of biocomponents, provides electrocatalytic activity against a variety of molecules, and improves electron transfer. To date, this type of modification is based on the irreversible deposition of NTCs on the surface through strategies that are poorly compatible with electrode reuse. However, NTCs are a highly porous material and NTC-modified electrodes are likely to promote significant levels of nonspecific adsorption and / or electrodeposition of biomolecules and / or biomolecules, which could induce cross contamination between samples under study and affect specificity. and reproducibility of the measurement protocol. This drawback has often been eluded by combining NTCs with electrically charged polymers capable of repelling negative / positive charge molecules.

On the other hand, using carboxylated NTCs (with surface carboxyl groups) dispersed in aqueous medium, a strong tendency is observed to adsorb nonspecifically on protein coated surfaces. In this invention, this capacity is used to produce NTC-coated PMs and the subsequent magnetic capture of these PM / NTC complexes for the production of NTC-modified electrodes. The production protocol is extremely fast, easy to carry out, and does not require the use of organic solvents avoiding harmful effects on the integrity of the electrodes. This minimizes exposure to solvents and in turn is beneficial to the environment at the level of waste management.

The process described in this invention is based on the use of carbon nanotubes (NTC), regardless of their origin, production method, composition or characteristics, as long as they are soluble in aqueous medium. These can be NTCs that have undergone a treatment (physical / chemical) that makes them hydrophilic / water soluble (for example, but not exclusively, generation of surface carboxyl groups by acid treatment), or NTCs that have been chemically modified to incorporate hydrophilic / water-soluble groups (for example, but not exclusively, chemical incorporation of ethylene glycol groups).

In this procedure, the NTCs are adsorbed unspecifically on the surface of magnetic microparticles (PM). It can be PM from 1 to several microns in diameter, regardless of origin, composition

or manufacturing process, as long as they are soluble in aqueous medium. Such PM may be protein coated PM, but PM with other surfaces / coatings could also be used (for example, but not exclusively, positively or negatively charged PM, polymer coated PM, metal coated PM, or PM exhibiting on surface reactive chemical groups).

The process may include, in addition to or as an alternative to the nonspecific adsorption of the NTCs, their chemical conjugation, or the stabilization of the PM / NTC complexes by any other means. To this end, PM and / or NTC modified with reactive groups (for example, but not exclusively, PM or NTC that exhibit succinimido groups, biotin molecules, etc.) can be used so that they react with NH2- groups, molecules of streptavidite, etc., present or incorporated in the surface of NTC or PM), or chemically conjugate PM and NTC in the presence of suitable reagents.

The device to be modified must incorporate, for example under or in its vicinity, a magnet or a magnetic field generator of any kind. This should ensure that the PM / NTC complexes are deposited directly on the sensor surface, working electrode, etc. The invention encompasses devices of any size, geometry, shape or material. These may be flat geometry devices, such as, but not exclusively, screen-printed electrodes and / or microelectrodes manufactured using silicon technology. However, the process object of the invention is capable of being applicable to different devices, such as carbon paste, graphite, NTC or similar electrodes, which may include in its composition other compounds (polymers, adhesive materials, conductive materials, etc.) or nanomaterials (nanoparticles / nanowires / ect. of any material), and that can integrate a magnet or the like.

In the case of wanting to reuse the devices after taking measurements by eliminating the PM / NTC complexes, the magnet is reversibly incorporated. That is, after the deposition of the PM / NTC and / or the taking of measures can be withdrawn.

For the production of the PM / NTC complexes and the modification of the devices, the procedure consists in mixing the selected volumes of both components. The relative amounts and / or proportions of both components may be varied and will depend on the application. The mixture is deposited (immediately or after incubation) on at least one of the electrodes of the device (for example, but not exclusively, a working electrode) that wants to be modified with NTC and that is being subjected to the effect of a magnet or a magnetic field generator located on the underside of the electrode. The volume or amount of PM / NTC deposited may be varied and will depend on the size, geometry and characteristics of the device to be modified, as well as the intended application. Thanks to the effect of the magnetic field, the PM / NTCs are deposited on the surface of the device and in contact with it. This sediment can be subjected to a subsequent wash with the desired aqueous / saline solutions.

In order to guarantee the reuse of the devices by eliminating the PM / NTC, the surface modified by the described procedure must not be dried.

The modified device can be used to take any type of electrochemical measurements including, but not exclusively, amperometric, voltammetric, impedimetric and / or conductimetric.

Description of the drawings

To complement the description that is being made and in order to help a better understanding of the characteristics of the invention, according to a preferred example of practical implementation thereof, a set of drawings is attached as an integral part of said description. where, for illustrative and non-limiting purposes, the following has been represented:

Figure 1. Shows a graph of the current generated in unmodified electrodes (bare SPE) or modi fi ed with 5 μl of PM and increasing amounts of NTC (0-7.5 μl NTC, 1 mg / ml). Cyclic voltammetry in 250 μM of ferrocyanide (dark bars) or in PBS (background current, light bars).

Figure 2. It shows a graph of the current generated in the unmodified electrodes (bare SPE) or modified with 5 μl of NTC and increasing amounts of PM (1-10 μl). Cyclic voltammetry in 250 μM ferrocyanide (dark bars)

or in PBS (background current, clear bars).

Figure 3. It shows cyclic voltamograms obtained for increasing concentrations of dopamine (DA), dissolved in PBS, on an unmodified electrode.

Figure 4. It shows cyclic voltamograms obtained for increasing concentrations of DA, dissolved in PBS, on a modified electrode with 10 μl of PM and 5 μl of NTC deposited by magnetic entrapment.

Figure 5. It shows a graph with peak current values obtained for increasing concentrations of DA in modified and unmodified electrodes.

Figure 6. Shows a graph of a difference pulse voltammetry (DPV) obtained in dopamine (DA) and uric acid (AU) measured on an unmodified electrode.

Figure 7. Shows a graph of a difference in pulse voltammetry (DPV) obtained in dopamine (DA) and in uric acid (AU) measured on a modified electrode with PM / NTC.

Preferred Embodiment of the Invention

In view of the figures, a preferred embodiment of the process object of this invention is described below.

Single wall NTC (SWNTC) modified with carboxyl groups (-COOH) on their surface were used. The NTCs were resuspended in Phosphate Buffered Saline (PBS) at a final concentration of 1 mg / ml and dispersed by sonication for at least 30 minutes at room temperature. The suspension was then stirred using a vortex for 2 minutes. These NTCs are soluble in aqueous medium up to 1 mg / ml; they have an average individual diameter of 1.4 nm ± 0.1 nm and form beams of 4-5 nm x 0.5-1.5 microns. At the beginning of each work day, and in order to ensure their optimal functioning, the NTCs were sonicated for 15 minutes, followed by vortexing for another 1 minute.

The PM were 2.8 microns in diameter and were coated with protein. PMPM were received at an approximate concentration of E 3-3.5 x 108 particles per milliliter (equivalent to 3-3.5 x 105 PM, approximately 5 mg, per microliter). The PM were stirred using a vortex for one minute, to completely resuspend them before use, and the necessary volume was transferred to an Eppendorf tube. The PM were then concentrated with the help of a magnet or a first magnetic field generator, the supernatant was removed, the PM was washed 3 times with PBS (10 mM Phosphate Buffer Saline, pH 7.4) and resuspended in PBS at chosen concentration.

Electronic devices consisting of flat screen-printed electrodes composed of a working electrode (1.6 mm in diameter) and a gold auxiliary electrode, and an Ag / AgCl reference electrode were used, all of them printed on a ceramic substrate. Prior to use, the electrodes were electrochemically activated by cyclic voltammetry between 0 and 1.4 V in 1M H2SO4 until a stable signal was obtained. Subsequent characterization was carried out by cyclic voltammetry in 0.1 M K3 [Fe (CN) 6].

In order to carry out the magnetic entrapment, a cylindrical magnet of 1 mm diameter was fixed under the working electrode as a second magnetic field generator.

Once the detection or measurement has been carried out using the electronic device with the coated electrode, the second magnetic field generator is removed from the back of the working electrode to release the previously produced coating on the working electrode; leaving the device in its original state.

Example 1

Efficiency of electrodes modi fi ed by magnetic entrapment of increasing amounts of NTC

An electrode, the working electrode, was coated with a fixed amount of PM (1.5 x 106 PM), previously incubated with increasing amounts of NTC (1-10 μg) resulting in a suspension mixture. Said mixture was deposited on the working electrode, under which the second magnetic field generator had been placed. The precipitate formed by PM and NTC on the working electrode, visible to the naked eye, was washed with PBS without being altered. The efficiency of the modified electrode was then studied by cyclic voltammetry (from -0.1 to +0.45 V, at 100 mV scanning speed) in PBS (negative control / background current) and in 250 μM potassium ferrocyanide.

As summarized in Figure 1, the entrapment of PM without NTC generates partial passivation of the electrode, increase in the background current in PBS and decrease in the current recorded in ferrocyanide. On the other hand, entrapment of increasing amounts of NTC results in an additional increase in the background current in PBS, whose value is directly related to the amount of NTCs captured, and induces the appearance of a pre-peak between -0.1 and 0 V. In the presence of ferricyanide, entrapment of increasing amounts of NTC correlates with a linear increase in the signal recorded in ferricyanide for amounts between 1 and 5 μg of NTC.

Example 2

Efficiency of electrodes modified by magnetic entrapment by increasing amounts of PM

An electrode, the working electrode, was coated with a fixed amount of NTC (5 μg) by magnetic entrapment using a variable number of PM (0-3 x 106 PM). The reagents, electrodes and experimental procedure are similar to those described in example 1.

As seen in Figure 2, the lowest PM numbers tested generated small deposits on the electrode surface. In these cases, most of the added NTCs were not trapped and were removed during washing. For the electrodes used, it was necessary to use a minimum of 2 μl of PM for NTC trapping so that the modified electrodes generated signals consistently higher than those recorded on the unmodified electrodes. The increase in the amount of PM used is correlated with a greater amount of trapped NTC. This translates into a decrease in the amount of NTC removed during the washing phases and simultaneous increase in the background current recorded in PBS and the peak current in ferricyanide. From 10 μl of PM, however, signal saturation is detected. This corresponds to the total coating of the electrode surface with PM / NTC. Under these conditions, ferricyanide voltammetry generates a peak 407% higher than the peak generated on an unmodified electrode.

Example 3

Dopamine (DA) detection using electrodes modified by PM / NTC magnetic entrapment

The third example includes the detection of an electroactive molecule of clinical interest, dopamine (DA), using electrodes modified with PM / NTC by magnetic entrapment. DA is a neurotransmitter released by the hypothalamus and the malfunction of its activity has been linked to several neurodegenerative disorders, including anorexia and bulimia, Parkinson's and Alzheimer's diseases, and schizophrenia. The reagents, electrodes and experimental procedure are similar to those described in Example 1. In this case the surface was modified with 3x106 PM resuspended in 5 μg of NTC.

The DA was dissolved in PBS at different final concentrations and was analyzed by cyclic voltammetry using parallel unmodified electrodes, as seen in Figure 3, and electrodes modified with PM / NTC, as seen in Figure 4 In the unmodified electrodes, the DA generates an oxidation peak at 0.2 V (vs. Ag / AgCl) and a reduction peak much less than -0.05 V (vs. Ag / AgCl). As other authors have observed previously, the oxidation of DA is not very reversible, because the oxidized product adsorbs on the surface of the electrode. In the case of the electrode modified with PM / NTC, the recorded bottom currents are higher, in line with the increase in the electrode surface due to the deposition of the NTC. The separation between peaks is 0.10 V for the modified electrode, compared to 0.15 V for the unmodified electrode. This significant improvement denotes the strong catalytic activity of the modified surface towards AD. The increase in peak current, on the other hand, can be attributed to a combined effect of the surface increase in the modified electrode, the accumulation of positively charged DA on the electrode surface, which thanks to the NTCs is negatively charged, and the electrocatalytic activity of the modified electrode.

For the two types of electrodes (modified and unmodified), the oxidation peak current increases with the concentration of DA. However, the reversibility of the reaction improves on the electrodes modified with NTC, and so does the detectability of DA. For example, the recorded signals are, for all tested DA concentrations, 2.6 to 5 times higher in the modified electrodes than the signals generated in the unmodified electrodes. Figure 5 shows the average data, calculated from the results of three independent electrodes. The detection limit, calculated as the average of at least five targets plus three times their standard deviation, improves from 1.69 μM in the electrodes without modifying to 0.71 μM when electrodes with PM / NTC are used. The sensitivity of the test, measured as the slope of the linear part of the graph, also improves on a modified surface with PM / NTC (30 vs 9 nAmp / μM DA).

Example 4

Simultaneous detection of dopamine and uric acid using electrodes modified by magnetic entrapment of PM / NTC

The main limitation of the detection of AD is the interference of components such as uric acid (AU), present in real samples at concentrations higher than DA. The AU oxidizes in most electrodes to potentials so close to those of the DA that the peaks generated by both compounds are hardly distinguishable. The incorporation of NTC to the electrode usually improves the resolution of the peaks generated by the DA and the AU. In this example we compare the detection by Differential Pulse Voltammetry (DPV) of DA and AU, separately or mixed at a concentration of 200 μM each, the electrodes unmodified or modified with PM / NTC already described in example 3.

As illustrated in Figures 6 and 7, DAyAU analyzed separately generate higher oxidation peaks in electrodes modified with PM / NTC than in unmodified electrodes (9.77 vs. 3.91 μA for DA and 6.53 vs. 1.11 μA for the AU, in modi fi ed / unmodified electrodes respectively). This effect is more evident for the AU, which generates a much clearer and almost 6 times higher peak in the modified electrode. The peak potential of the AU shifts 64 mV negatively on the modified electrodes, which confirms their catalytic activity.

The simultaneous detection of DA and AU in the unmodified electrodes evidences an important level of electrocatalysis of the DA by the AU, as can be seen in Figure 6. This translates into an increase in the height of the DA peak when measured in the presence of AU at equimolar concentration, with respect to the current generated by a similar concentration of DA alone. At the same time, the AU peak decreases in height in the presence of DA and becomes almost undetectable. On the contrary, in the electrodes modified with PM / NTC the two peaks are clearly separated and there are almost no differences in the height of the peaks that can be attributed to the catalysis of the DA by the AU as can be seen in the Figure 7.

Claims (10)

1. Electrode coating method of an electronic device comprising: a) activating and / or washing a working electrode to be coated, b) dispersing soluble carbon nanotubes (NTC) in an aqueous medium at a defined concentration between 0.1 and 10 mg / ml, c) concentrate soluble magnetic particles (PM) in aqueous medium using a mag field generated by a first generator of magnetic fields, d) remove supernatant, e) wash the magnetic particles (PM) with the aqueous medium in which the NTCs have been dispersed and repeat c) and d), f) resuspend the result of the previous phase in a volume of NTC dispersion prepared in b), g) fix a second magnetic field generator on the underside of the work electrode to be coated, h) coat the work electrode by deposition of the result of (f) on a face to be coated with the electrode of work.

2.

Method according to claim 1 characterized in that it includes removing the magnetic field generator causing the detachment of the coating present on the working electrode and washing the working electrode.

3.

Method according to claim 1 characterized in that the PMs are coated by at least one protein.

Four.

Method according to claim 1 characterized in that the aqueous medium of b) is a saline solution.

5.

Method according to any of the preceding claims characterized in that the NTCs are modified.

6.

Method according to claim 6 characterized in that the NTCs are functionalized.

7.

Electrode obtainable by the method described in any one of claims 1-6.

8.

Electronic device characterized in that it comprises the electrode described in claim 7.

9. Use of the electronic device described in the preceding claim for performing analyte detection and measurement. SPANISH OFFICE OF THE PATENTS AND BRAND Application no .: 200931261 SPAIN Date of submission of the application: 23.12.2009 Priority Date: REPORT ON THE STATE OF THE TECHNIQUE 51 Int. Cl.: B81C1 / 00 (2006.01) B82Y15 / 00 (2011.01) RELEVANT DOCUMENTS

Category

Documents cited Claims Affected

X

US 2007275627 A1 (KOREA ADVANCED INST SCI & TECH) 29.11.2007, 1-9

paragraphs [2], [12], [32-55]; claims 1-6; Figure 1.

X

WO 2004052489 A2 (UNIV NORTH CAROLINA et al.) 24.06.2004, 1,3,5-9

summary; page 11, lines 7-17; Figure 1; claim 3.

TO

WO 2008066965 A2 (UNIV CALIFORNIA et al.) 05.06.2008, 3.5.6

page 27, line 25 - page 28, line 4; figure 26.

Category of the documents cited X: of particular relevance Y: of particular relevance combined with other / s of the same category A: reflects the state of the art O: refers to unwritten disclosure P: published between the priority date and the date of priority submission of the application E: previous document, but published after the date of submission of the application

This report has been prepared • for all claims • for claims no:

Date of realization of the report 03.10.2011

Examiner E. P. Pina Martínez Page 1/4

REPORT OF THE STATE OF THE TECHNIQUE Application number: 200931261 Minimum documentation sought (classification system followed by classification symbols) B81C, B82Y Electronic databases consulted during the search (name of the database and, if possible, terms of search used) INVENES, EPODOC, WPI State of the Art Report Page 2/4  WRITTEN OPINION Application number: 200931261 Date of Written Opinion: 03.10.2011 Statement

Novelty (Art. 6.1 LP 11/1986)

Claims Claims 1-9 IF NOT

Inventive activity (Art. 8.1 LP11 / 1986)

Claims Claims 1-9 IF NOT

The application is considered to comply with the industrial application requirement. This requirement was evaluated during the formal and technical examination phase of the application (Article 31.2 Law 11/1986).  Opinion Base.- This opinion has been made on the basis of the patent application as published. State of the Art Report Page 3/4  WRITTEN OPINION Application number: 200931261 1. Documents considered.- The documents belonging to the state of the art taken into consideration for the realization of this opinion are listed below.

Document

Publication or Identification Number publication date

D01

US 2007275627 A1 (KOREA ADVANCED INST SCI & TECH) 11/29/2007

D02

WO 2008066965 A2 (UNIV CALIFORNIA et al.) 05.06.2008

2. Statement motivated according to articles 29.6 and 29.7 of the Regulations for the execution of Law 11/1986, of March 20, on Patents on novelty and inventive activity; quotes and explanations in support of this statement Claim 1 Document D01 describes the following procedure (references in brackets refer to D01): Electrode manufacturing process of an electronic device comprising the following steps (Reiv. 1-6):

to.

 Disperse carbon nanotubes (NTC) in an aqueous medium at a defined concentration between 0.1 and 10 mgl / ml (para. [48]).

b.

 add magnetic particles (PM) in the aqueous medium in which the NTCs have been dispersed (para [49] - [50]).

C.

remove the supernatant (para. [50])

d.

 fix a magnetic field generator on the underside of the working electrode to be coated (fig. 1b, para. [55]).

and.

 coating the working electrode by deposition of the result of (c) on a face to be coated of the working electrode (para. [52]).

It follows that the essential steps of the process by which aggregates of nanotubes and magnetic particles are formed by dispersion for subsequent deposition controlled by a magnetic field on a substrate constituting the electrode, are also described in D01. As for the differences observed between both methods, these reside in stages, not explicitly described in D01, but which are considered sufficiently known and of obvious application to a person skilled in the art, such as electrode washing or the previous concentration of magnetic particles. by using a magnetic field generator. Therefore, it is considered that the independent claim does not satisfy the inventive activity requirement of Art. 8.1 of Patent Law 11/86. Claims 2-6 The dependent claims do not comprise additional steps of the method claimed in the first claim that are different from that described in D01 or that confer said method inventive activity against the prior art. In particular, the step of claim 2 referring to the removal of the magnetic field in order to detach the layer of NTC / PM assemblies, would be an obvious step for a person skilled in the art, who would apply it without inventive effort to the extent in which the effects of the application or removal of a magnetic field on a magnetic material are known. As for claims 3, 5, 6 regarding the functionalization of the nanotubes, these are particularizations of the method to known materials (see document D02) that do not involve inventive activity (Art. 8.1 LP). Claims 7-8 These claims also do not satisfy the requirement of inventive activity (Art. 8.1 LP) because it is the result of the application of the previous method, which does not present inventive activity. Claim 9 The use for the detection and measurement of analytes of an electronic device comprising an electrode obtained by the claimed method, is known in the prior art (see eg D02, fig. 26) whereby claim 9 also it lacks the requirement of inventive activity (Art. 8.1 LP). In conclusion, in view of the prior art, the application does not satisfy the patentability requirements set forth in Art. 4.1 LP. State of the Art Report Page 4/4