Magnetic nanoparticle based electrochemical analysis system

Abstract

The invention relates to a magnetic nanoparticle-based electrochemical analysis system consisting of at least one application device (A) and sample collection element (B) that can be used to capture and analyze the target components to be analyzed in liquid samples at a high rate.

Description

[0001] MAGNETIC NANOPARTICLE BASED ELECTROCHEMICAL ANALYSIS SYSTEM

[0002] Technical Field

[0003] The invention relates to a magnetic nanoparticle-based electrochemical analysis system that can be used to capture and analyze the target components to be analyzed in liquid samples at a high rate and the system sub-components used within said system . The system embodiment of the invention can create a technical solution that can enable analysis , especially in portable devices .

[0004] State of the Art

[0005] Sensors are devices consisting o f an active sensor system and signal converter units . These devices have a very wide range of uses in industrial processes such as control , protection, and imaging .

[0006] The definition of electrochemical sensors ( electrochemical sensor systems ) brought by TUPAC is "Reduced devices that selectively and reversibly respond to chemical compounds or ions and create concentration-dependent electrical signals are called electrochemical sensors" .

[0007] In summary, electrochemical sensors are analytical devices comprising a biological diagnostic element and a suitable converter . The converter trans forms the chemical change resulting from the interaction of the molecules with the receptor into an output signal . The receptor agent may be an enzyme , a microorganism, a tissue or a bioligand, which may be an antibody, a nucleic acid, or a synthetic sensor . The main application areas are quality control in agriculture , food and pharmaceutical industry, circumferential pollution / biological warfare agents and medical diagnostic methods .

[0008] In parallel with the advances in the synthesis and characteri zation of nanostructured materials , there have been signi ficant developments in sensor design and applications . Recently, many nanostructured electronic materials have been developed with their remarkable electrical , optical , and mechanical properties and have been used in di f ferent applications . In addition, nanostructured materials have started to be used in electrochemical sensors due to their superior electro-catalytic properties .

[0009] Nanoparticles have a high surface area as well as their extraordinary optical , electronic, magnetic, biocompatibility, etc . , which has enabled them to be used in numerous applications .

[0010] These developments may allow nanoparticles to be used to capture and analyze the target components to be analyzed in liquid samples at a high rate . These applications are included in the state of the art . Within these applications , the magnetic nanoparticles that can bind to them with the relevant target component can be collected on the nanoparticles by interacting with the target components .

[0011] For example , in the analysis o f the immunosensor structure , the target component can perform a change by binding with biological receptors such as antibody, antibody fragment , and aptamer . In electrochemical measurements , the signals vary according to the number of components captured by the receptors . According to the electrochemical analysis applications included in the ordinary state of the art , after the sample i s collected from the field, it i s brought to the environment where the analysis is performed, and analysis is performed in the laboratory .

[0012] However, in this case , it can create a handicap since it cannot be analyzed in the environment where the sample is taken . While the sample is first collected, then transported to the laboratory, and again trans ferred to the environment where the analysis will be performed, the probability of contamination and deterioration of the sample where the analysis will be performed increases and therefore the accuracy of the analysis decreases .

[0013] I f existing systems are used, the use of additional elements such as micropipettes , especially during sample collection and trans fer processes , signi ficantly increases the risk of contamination . Each additional transfer to be made after the sample is collected may cause an increase in this risk .

[0014] Again, analyzing the sample to be analyzed in the laboratory requires both the laboratory and the technical expert to perform the analysis . This will both increase the implementation costs and cause the cost of the analysis to increase .

[0015] The fact that the analysis should only be performed by expert personnel in the laboratory can prevent the analysis from being performed simply by normal users .

[0016] Since the applications included in the present art require the use of complex laboratory devices and experienced personnel , the cost of each test increases signi ficantly . The ordinary state of the art includes electrochemical sensor structures that are in the form of kits and can be used in the field . However, it may be insuf ficient in terms of ef ficiency in these applications .

[0017] Again, although existing printed electrochemical biosensors are planned for field applications , they generally allow experiments to be performed at room temperature in laboratory environments .

[0018] For example , patent application TR 2014 / 03992 mentions an electrochemical sensor array and apparatus .

[0019] It is understood that the apparatus comprises at least one upper layer suitable for use for analysis of at least one sample by an electrochemical sensor array, at least one inlet and at least one outlet opening in the upper layer, at least one lower layer with at least one recess , at least one double-sided adhesive membrane compatible with the recess in the lower layer, at least one working electrode fixed to the lower layer by means of said adhesive membrane , at least one reference electrode .

[0020] Problems to be Solved by the Invention

[0021] The obj ect of the invention is to create a magnetic nanoparticle-based electrochemical analysis system that can be used to capture and analyze the target components to be analyzed in liquid samples at a high rate .

[0022] In this way, the compulsory need for a laboratory or technical personnel to perform the application could be eliminated in order for the system to be used for analysis . By using the electrochemical analysis system of the invention, the need for trans ferring the samples taken to a transportation environment to the environment where the analysis will be performed and trans ferring them to the test environments such as the kit where the analysis is performed in this environment has been eliminated . In this way, possible contamination, deterioration, etc . that may occur due to trans fer, transportation, etc . are minimi zed .

[0023] Within the embodiment of the invention, the sensor is integrated into the tubes . In this way, it may be suf ficient to take a sample into the tube to perform the application . In this way, it will be possible to perform direct analysis in a limited si ze mass application area that the user can carry with them .

[0024] Again, within the preferred application of the invention, it was possible to keep the nanoparticles on the biosensor surface with a low waste rate with the reverse hollow cone structure formed on the tube floor . Thanks to this design, the ef ficiency of the system has increased .

[0025] Again, within the scope o f the invention, with the electromagnetic field module placed under the biosensor, it has been possible to analyze in a closed system that is kept away from external factors and provides ease of use by collecting from the outside of the tube .

[0026] Thus , the application of the solution of the invention can be made outside the laboratory and in the field . Description of the Figures

[0027] Figure 1 . A perspective view of the tube sensor integrated cover system,

[0028] Figure 2 . A disassembled perspective view of the base part ,

[0029] Figure 3 . A disassembled top view of the base part ,

[0030] Figure 4 . A side view of the tube sensor integrated cover system,

[0031] Figure 5 . A perspective view o f the magnetic nanoparticlebased electrochemical analysis system,

[0032] Figure 6 . A front view of the magnetic nanoparticle-based electrochemical analysis system,

[0033] Figure 7 . A front view of the magnetic nanoparticle-based electrochemical analysis system,

[0034] Figure 8 . An integrated perspective view of the magnetic nanoparticle-based electrochemical analysis system after rotation,

[0035] Figure 9 . An integrated side view of the magnetic nanoparticle-based electrochemical analysis system

[0036] Description of References in Figures

[0037] A. Application device

[0038] B . Sample collection element

[0039] 1 . Tube

[0040] 2 . Base part

[0041] 3 . Printed electrochemical sensor

[0042] 4 . Working cavity

[0043] 5 . Mounting channel

[0044] 6 . Reference electrode

[0045] 7 . Counter electrode

[0046] 8 . Working electrode

[0047] 9 . Electromagnetic ef fect module

[0048] 10 . Rotation Module 11. Potentiostat-containing analysis module

[0049] 12. Analysis module

[0050] 13. Input module

[0051] 14. Electrochemical sensor device integration section

[0052] 15. Connection cables

[0053] 16. Electrode connection section

[0054] 17. Connection electrodes

[0055] Description of the Invention

[0056] The invention relates to a magnetic nanoparticle-based electrochemical analysis system consisting of at least one application device (A) and sample collection element (B) that can be used to capture and analyze the target components to be analyzed in liquid samples at a high rate.

[0057] The sample collection element (B) of the invention can be configured as an external part and the analysis process can be completed by connecting to the application device (A) after sampling. Within the different embodiments of the invention, the sample collection element (B) and the application device (A) may be integratedly configured.

[0058] The sample collection element (B) structure comprises at least one tube (1) into which the sample to be analyzed can be taken directly, at least one base part (2) intended to be connected to the cavity of the tube (1) , at least one working cavity (4) formed on the side of the base part (2) connected to the cavity of the tube (1) and at least one printed electrochemical sensor (3) associated with the working cavity (4) .

[0059] After sampling, the base part (2) and the tube (1) can be connected and closed. After this closure, the sample taken into the tube (1) can be isolated from the outside environment .

[0060] According to Figure 2, the base part (2) is formed in a form that will have a circular cross-sectional area. There is at least one mounting channel (5) in the structure of the base part (2) . The mounting channel (5) takes the tube (1) and closes the system to the outside environment. The mounting channel (5) is formed in the form of a circumferential channel according to the preferred embodiment of the invention.

[0061] According to Figure 2, the working cavity (4) is configured in the form of a cone. At least one sensor (3) is associated with the part of the working cavity (4) formed in the form of a cone with the narrowest cross-sectional area. According to Figure 1, the part where the sensor (3) is associated is the ground of the working cavity (4) in the form of a cone.

[0062] That is, the sensor is positioned on the ground of a working cavity (4) configured in the form of an inverted cone upwards from the region to be analyzed. Within the preferred embodiment of the invention, the base part (2) is made of polymer and the target component to which it is attached aims to be connected to the tube (1) containing the solution with attached nanoparticles.

[0063] With the reverse cavity cone structure described above, it can be ensured that the waste rate of nanoparticles on the biosensor surface is kept low. Thanks to this embodiment, the collection of magnetic particles in the center is facilitated. Again, with the electromagnetic field module placed under the biosensor, it has been possible to analyze in a closed system that is kept away from external factors and provides ease of use by collecting from the outside of the tube ( 1 ) .

[0064] Figure 3 shows the base part (2) in the cone structure with the working cavity (4) visible. In this embodiment, the reference electrode (6) , the counter electrode (7) and the working electrode (8) are shown in the form of a cone positioned on the ground of the working cavity (4) configured .

[0065] This embodiment is more especially configured so that the working electrode (8) is at the center and the reference electrode (6) , and the counter electrode (7) are at the sides.

[0066] The electrochemical sensor (3) formed in the form of a printed electrode according to Figure 1 will be integrated into the tube in a structure that will face the analysis area in parallel with the lower surface of the base part (2) . In order to accurately collect the nanoparticles in the analysis area of the sensor (3) , an inverted cone structure with an increasing diameter will be created around the analysis surface of the sensor (3) . Thus, it will be possible for the electromagnetic field to directly capture all nanoparticles and pull them towards the center.

[0067] Figure 5 shows the case where the sample collection element (B) is connected to the application device (A) . Within this application, the user collects the sample to be analyzed with the sample collection element (B) and completes the analysis by connecting it to the application device (A) .

[0068] According to Figure 5, the sample collection element (B) is connected to the application device (A) from the end where it contains the base part (2) . At least one electromagnetic effect module (9) is configured in the part of the application device (A) that interacts with the base part (2) . When the electromagnetic effect module (9) is activated, the magnetic nanoparticles in the tube (1) can be collected on the sensor surface

[0069] The electromagnetic effect module (9) is a module that creates a magnetic effect when an electric current is given. It usually has a rounded tip and shows the direction in which the application will be made.

[0070] The module that physically holds the tube (1) will be able to perform a circular rotational movement so that the nanoparticles in the solution can be completely collected and mixed .

[0071] In order to ensure this rotation, the application device (A) comprises at least one rotation module (10) in its structure.

[0072] Again, the rotation module (10) ensures that the sample collection element (B) is integrated into the analysis module (12) by moving to the base of the application device (A) . Figure 8 shows the integrated state of the sample collection element (B) and the application device (A) .

[0073] According to Figure 5, the analysis module (11) with the least potentiostat content was formed within the analysis module (12) in the base section of the application device (A) . After the sample collection element (B) is integrated with the base part (A) of the device after rotation, the potentiostatcontaining analysis module (11) may interact with the sample collection element (B) functional units.

[0074] According to Figure 6, the analysis module (12) comprises at least one input module (13) in its structure. According to Figure 7, the analysis module (12) comprises the connection cables (15) and the electrode connection section (16) in its structure.

[0075] According to Figure 7, the application device (A) comprises at least one electrochemical sensor device integration section (14) positioned to be associated with the base part (2) in the section where the sample collection element (B) is connected. This embodiment enables the integration of the sensors formed within the base part (2) .

[0076] The sample collection element (B) can be connected to the application device (A) by compression thanks to the analysis module (12) compressing the base part (2) . Since the tube (1) and the base part (2) can be connected and disassembled separately, the tube (1) can be rotated to be separated from the base part (2) and another tube (1) filled with a new solution to be treated can be integrated.

[0077] With this method, processes such as changing and shaking the tube (1) can be performed to wash the nanoparticles.

[0078] For the washed magnetic nanoparticles, the tube (1) containing the new solution can be inserted and disassembled into the system.

[0079] The invention is a solution for capturing and analyzing the target components to be analyzed in liquid samples at a high rate. The details of the analysis method of the invention are stated below.

[0080] In the analysis of the immunosensor structure, the target component aims to perform a change by binding with biological receptors such as antibody, antibody fragment, and aptamer. In electrochemical measurements, the signals vary according to the number of components captured by the receptors. In this context,

[0081] The magnetic nanoparticles that can bind to them with the relevant target component are freeze-dried in the tube (1) (preferably 50mL Falcon®) . Within the preferred embodiment of the invention, an electrically conductive material is coated on the magnetic core and the receptor can be connected to it.

[0082] Therefore, the shelf life of the biosensor will be long. Then, the solution containing the target component will be transferred to the tube (1) , which contains the nanoparticles. After the solution is transferred into the tube, the magnetic nanoparticles will be dispersed in the solution. In this direction, the mixing process can be started by placing the tube in equipment such as a vortex mixer and shaker. During the mixing process, the magnetic nanoparticles will interact with all the target components in the solution and collect them on the nanoparticles. Then, the standard cover of the tube will be removed. The base part (2) , which has a printed electrochemical sensor at the bottom, will be mounted.

[0083] This connection is provided so that the sensor with the narrowest cross-sectional area (preferably the ground part) of the working cavity (4) within the base part (2) is positioned upwards. The tube (1) containing the solution with the nanoparticles attached to the target component to which this base part (2) structure is attached will be inserted. The integrated base part-tube system will be attached to the application device (A) where it will be placed vertically. An electromagnetic effect module (9) will be placed just behind the region to be analyzed at the integration point of the base part ( 2 ) . This structure will be activated with the command given to the device (A) and will create an electromagnetic ef fect . Thus , the magnetic nanoparticles will be collected on the analysis zone of the biosensor integrated in the cover . The system in which the tube ( 1 ) is integrated will be able to be vertical or upside down with 180-degree movements . Magnetic nanoparticles that cannot be collected in the upright state will become upright and upside down with repeated 180-degree movement and will create a mixture movement and all nanoparticles will be collected on the surface .

[0084] In order to completely clean the nanoparticles from the sample solution, after the sample solution is removed, the buf fer solution or another tube ( 1 ) with pure content can be reintegrated into the base part ( 2 ) and the washing process can be performed with 180-degree movements . Then, it will be integrated into the base part ( 2 ) with the tube ( 1 ) with the probe solution that allows the analysis to be performed, and the system will be turned upside down . Thus , while there is the analysis solution on the sensor surface , electrochemical analysis can be performed with the command given to the device (A) .

[0085] Thus , a system that enables analysis in the field without experts and laboratories has been created . In the system design of the invention, the way the biosensor is integrated into the cover of the 50 mL Falcon® tube ( 1 ) and the ability to shoot with the electromagnetic module will enable the extraction and analysis processes to be analyzed on the same product without contacting the external environment and away from contamination . While the nanoparticle-based system accelerates the binding of the target component , it will also allow the analysis to be performed by connecting magnetically to the biosensor electrode . With this electromagnetic module , extraction and analysis can be performed in the tube (1) with external electronic intervention.

Claims

CLAIMS l. A magnetic nanoparticle-based electrochemical analysis system comprising at least one application device (A) and sample collection element (B) , which can be used to capture and analyze the target components to be analyzed in liquid samples at a high rate, characterized in that it comprises at least one tube (1) into which the sample to be analyzed can be taken directly, at least one base part (2) intended to be connected to the cavity of the tube (1) , at least one working cavity (4) formed on the side of the base part (2) connected to the cavity of the tube (1) , and a sample collection element (B) having at least one printed electrochemical sensor (3) associated with said working cavity ( 4 ) .

2. The magnetic nanoparticle-based electrochemical analysis system according to claim 1, characterized in that it comprises a base part (2) formed in a form having a circular cross-sectional area and provided with at least one mounting channel (5) for receiving the tube (1) .

3. The magnetic nanoparticle-based electrochemical analysis system according to claim 2, characterized in that it comprises the mounting channel (5) formed in the form of an circumferential channel.

4. The magnetic nanoparticle-based electrochemical analysis system according to claim 1, characterized in that it comprises the working cavity (4) structured in the form of a cone .

5. The magnetic nanoparticle-based electrochemical analysis system according to claim 1, characterized in that itcomprises the working cavity (4) to which at least one sensor (3) is associated with the part having the narrowest cross-sectional area.

6. The magnetic nanoparticle-based electrochemical analysis system according to claim 5, characterized in that the cone- shaped ground of the working cavity (4) is associated with the sensor (3) .

7. The magnetic nanoparticle-based electrochemical analysis system according to claim 5, characterized in that it comprises a reference electrode (6) , a counter electrode (7) and a working electrode (8) positioned on the ground of the working cavity (4) .

8. The magnetic nanoparticle-based electrochemical analysis system according to claim 7, characterized in that it is configured to have a working electrode (8) at the center, a reference electrode (6) and a counter electrode (7) at the sides .

9. The magnetic nanoparticle-based electrochemical analysis system according to claim 7 or 8, characterized in that it comprises an electrochemical sensor (3) integrated parallel to the bottom surface of the base part (2) such that the analysis area faces into the tube.

10. The magnetic nanoparticle-based electrochemical analysis system according to claim 1, characterized in that it comprises an application device (A) to which the sample collection element (B) is connected at the end of the base part ( 2 ) .

11. The magnetic nanoparticle-based electrochemical analysissystem according to claim 10, characterized in that it comprises an electromagnetic effect module (9) configured with at least one electromagnetic effect module (9) in the part where it interacts with the base part (2) .

12. The magnetic nanoparticle-based electrochemical analysis system according to claim 11, characterized in that it comprises an electromagnetic effect module (9) having a rounded end and configured to point in the direction of application .

13. The magnetic nanoparticle-based electrochemical analysis system according to claim 10, characterized in that it comprises the application device (A) equipped with at least one rotation module (10) .

14. The magnetic nanoparticle-based electrochemical analysis system according to claim 13, characterized in that it comprises a rotation module (10) for integrating the sample collection element (B) into the analysis module (12) by moving it to the base of the application device (A) .

15. The magnetic nanoparticle-based electrochemical analysis system according to claim 13, characterized in that it comprises an analysis module (12) comprising at least a potentiostat-containing analysis module (11) .

16. The magnetic nanoparticle-based electrochemical analysis system according to claim 13 or 15, characterized in that it comprises the analysis module (12) equipped with at least one input module (13) .

17. The magnetic nanoparticle-based electrochemical analysis system according to claim 13 or 15, characterized in that itcomprises the analysis module (12) provided with connection cables (15) and an electrode connection part (16) .

18. The magnetic nanoparticle-based electrochemical analysis system according to claim 10, characterized in that it comprises an application device (A) comprising at least one electrochemical sensor device integration part (14) positioned to be associated with the base part (2) in the section where the sample collection element (B) is connected .

19. A method of operating a magnetic nanoparticle-based electrochemical analysis system consisting of at least one application device (A) and sample collection element (B) , which can be used to capture and analyze the target components to be analyzed in liquid samples at a high rate, characterized in that it comprises the process steps of freeze-drying magnetic nanoparticles capable of binding with the target component in a tube (1) , Then, transferring the solution containing the target component to the tube (1) containing the nanoparticles, Removing the standard cover of the tube (1) and mounting the base part (2) , which has a printed electrochemical sensor at the bottom, Attaching the integrated base part-tube system vertically to the application device (A) where it will be placed, Creating an electromagnetic effect on the tube (1) by activating the device (A) on command, Moving the tube (1) to the upright or upside-down position with 180° movements by the application device (A) , Afterwards, integrating the tube (1) with the probe solution for the analysis into the base part (2) and putting the system upside down, Performing electrochemical analysis with the command givento the device (A) while the analysis solution is present on the sensor surface.

20. The method for operating the electrochemical analysis system according to claim 19, characterized in that it comprises the process step of providing, when connecting the base part (2) and the tube (1) , the working cavity (4) within the base part (2) in such a way that the sensor with the narrowest cross-sectional area of the upwardly inverted cone (preferably the ground part) is positioned.

21. The method of operating the electrochemical analysis system of claim 19, characterized in that a conductive material is coated on a magnetic core and the receptor is attached thereto.

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