ES2301416B1 - APPARATUS FOR THE ANALYSIS AND QUANTIFICATION OF THE ANALYTIC CONCENTRATION PRESENT IN A SAMPLE USING MAGNETORRESISTIVE SENSORS. - Google Patents

Abstract

Apparatus for the analysis and quantification of concentration of analyte present in a sample using sensors external magnetoresistive consisting of:

- a mechanical system (1);

- a magnetoresistive sensor (3);

- magnetization means (21 and 22);

where the mechanical system (1) has means so that the substrate (4) and the sensor (3) are at the shortest distance possible with each other and thus obtain a better reading; and where the magnetization means (21 and 22) can be external coils (21), a permanent magnet (22) or a combination of both.

Description

Apparatus for the analysis and quantification of concentration of analyte present in a sample using sensors magnetoresistive

Object of the invention

The present invention relates to an apparatus for the analysis and quantification of the nanoparticles that have remained fixed on the substrate after the biological test (tests lateral flow) by means of a magnetoresistive sensor external to the substrate and that uses a mechanical system that allows to approach the maximum substrate and magnetoresistive sensor.

Background of the invention

At present, for the detection of concentration of analytes in a sample there are several methods

First, the tests immunochromatographic These tests consist of very fast tests based on the immunological capture of a colored colloid during its passage through a membrane on which the antianalite (antibody, antigen, protein, etc.). They are widely used tools that, however, have certain disadvantages that make its use in certain applications not possible, since they do not allow quantifying, that is, determining what concentration of analyte is in the sample and its sensitivity is limited (depending on the analyte and reagents used on sensitivity limit is between 1 and 10 ng / ml). This causes that immunochromatographic tests are inadequate when required a very high sensitivity, as in the case of diseases infectious

To overcome these inconveniences it has been created a new technology based on the use of nanoparticles magnetic replacing traditional colloids. To measure the amount of magnetic nanoparticles that remain immobilized a high magnetic sensor is used in the test line sensitivity. In the patent US-6437563-B1 discloses the MAR ("Magnetic Assay Reader") technology, which is based on a inductive method The sample is subjected to an alternating magnetic field (typically 100 Oe, 100 kHz) created with the help of a core of ferrite with a very small gap between poles by which Insert a strip of cellulose with the sample. Two identical coils connected in series and opposition inside the gap register the induced voltage when the sample passes through them. He voltage without sample is zero, but the presence of nanoparticles  magnetic changes the mutual inductances and makes a voltage proportional to the amount of nanoparticles present in the sample. However, to create a magnetic field high enough, the hole in the core must be very small and this greatly limits the thickness of the cellulose strips used in the test.

In the patent US-2004171172-A1 discloses another inductive method for quantitative concentration analysis of analytes. Said method does not use a ferrite core to create the field, which does not have the limitation as to the thickness of the cellulose strips The excitation field is created by a conventional solenoid. Otherwise, the measurement method uses the Same principle as the previous patent.

In WO200127692 a device is disclosed in which molecular recognition occurs on the same sensor, which has been previously functionalized, that is, it is not a lateral flow test, as is the application of the object of the present patent. invention, but is framed in what in this field of the technique is known as lab-on-a-chip , that is, analysis within the chip in which the molecular recognition platform and magnetoresistive detection coincide.

It is not known by the inventors, subject matter experts, no system or device that contemplates the application of magnetoresistive sensors in flow tests side.

Description of the invention

The present invention relates to an apparatus for the analysis and quantification of the analyte concentration present in a sample using magnetoresistive sensors, according to Claim 1. Preferred embodiments of said method are defined in the dependent claims.

The apparatus is essentially composed of:

-

A Mechanic system.

-

A magnetoresistive sensor, which is a sensor whose resistance electric changes due to the presence of magnetic fields Dipolars produced by the particles.

-

Media of magnetization.

Where the mechanical system has two possible realizations In the first, the mechanical system is composed by a moving element that moves horizontally and a wheel that rotates on its axis. This mechanical system presses the substrate (typically a strip of cellulose) on the sensor magnetoresistive, so that the distance on the Z axis between substrate and sensor be the minimum. Similarly rotate the wheel so that finally the test line that contains the magnetic particles remain in the same position of the X axis as the sensor magnetoresistive

In the second embodiment, the displacement relative between the strip and the sensor is linear such that the Strip support moves linearly on the X axis. This support transports the strip at its bottom, and this passes through the upper part of the magnetoresistive sensor, which is raised by its support towards the strip.

On the other hand the magnetization means can be of two types:

one.

To the minus two external coils that generate a magnetic field that magnets the magnetic particles present in the substrate.

2.

To the minus a permanent magnet under the sensor, which creates a field magnetic on the particles, polarizing them. Magnetic field produced by the permanent magnet is perpendicular to the strip and the plane in which the sensor is located.

3.

A combination of the above.

The operation of the device subject to This specification is as follows:

Once the test has been carried out lateral flow in the cellulose strip (substrate) and particles magnetic tags that label the analyte have been trapped in the test line, it sticks to the wheel of the mechanical system or its linear support and is carried close to the sensor through the mechanical system, which allows:

to.

He displacement of the support where the sensor is.

b.

He spin of the wheel where the substrate or the linear displacement of the strip support.

Subsequently a magnetic field is applied with external coils or a permanent magnet that magnetize the Magnetic particles. As you move the relative positions of the substrate and sensor, magnetoresistive sensor resistance it will change when the test line is exactly over the sensor due to the dipole magnetic fields produced by the Magnetic particles. From the change of electrical resistance the amount of magnetic particles is deduced, and from there, the amount of the analyte they are tagging, which allows perform a quantification of the analyte concentration. This design allows to work with both static magnetic fields and Alternate

Brief description of the drawings

Then it goes on to describe very brief a series of drawings that help to better understand the invention and that expressly relate to an embodiment of said invention presented as a non-limiting example of is.

- Figure 1: Schematic view of the device for the analysis and quantification of the analyte concentration present in a sample using magnetoresistive sensors, in its realization with a rotating mechanical system.

- Figure 2: Detail of the mechanical system and the magnetoresistive sensor, in its realization with a mechanical system rotary, as an integral part of the object of this patent of invention

- Figure 3: Schematic view of the device for the analysis using a mechanical system in its realization linear.

- Figure 4: Variation graph of the resistance of the sensor with respect to the position of the strip with magnetization due to external coils.

- Figure 5: Variation graph of the resistance of the sensor with respect to the position of the strip with magnetization due to permanent magnets.

Preferred Embodiment of the Invention

As it is possible to observe in the figures attached, the apparatus for the analysis and quantification of the concentration of analyte present in a sample using sensors magnetoresistive, object of the present invention is composed by:

-

A mechanical system [1].

-

Media of magnetization [21 and 22].

-

A magnetoresistive sensor [3].

Where the mechanical system [1] comprises:

-

Media of displacement in the Z axis [11] of the magnetoresistive sensor [3].

-

Media of displacement in the X axis [10] of the strip or substrate [4].

These means act in such a way that the separation distance on the Z axis of the substrate [4] and the sensor magnetoresistive [3] is the minimum and the position of both is coincident on the X axis.

The displacement means on the X axis [10] of the strip or substrate [4] consists of one of the following media:

-

A wheel [12] rotating on a shaft [13].

-

A linear displacement element [14].

In figure 1 you can see how the means of displacement in the Z axis [11] of the magnetoresistive sensor [3] press the substrate [4] attached to the wheel [12] and the sensor magnetoresistive [3] so that the distance is minimal on the Z axis. Similarly, the wheel [12] rotates on its axis [13] so that finally the substrate [4] that contains the magnetic particles is in the same position of the X axis as the magnetoresistive sensor  [3].

On the other hand, in figure 3 we observe how the displacement means on the Z axis [11] of the sensor magnetoresistive [3] raise the sensor on the Z axis until the minimum distance from the linear displacement element [14] which incorporates the substrate [4] in its lower part.

The magnetization means [21 and 22] can be, at least one of the following means:

-

Two external coils [21].

-

A permanent magnet [22] under the magnetoresistive sensor [3].

Figure 4 shows the shape of the field magnetic B1 in the case of use of external coils [21]. In this case field B1 is longitudinal with respect to the substrate [4] and the variation of the resistance R with respect to the position [P] of the strip or substrate [4] will have the following form: first a sign peak positive, then a large negative variation and finally a new positive sign peak, all as the strip advances or  substrate [4] with respect to the sensor [3].

In figure 5 it is possible to observe the shape of the B2 magnetic field produced by the permanent magnet placed under the sensor [3]. This field B2 is perpendicular to the substrate [4] and the plane in which the sensor [3] is located. The presence of magnetic particles in the substrate [4] produces field lines perpendicular to the substrate, which implies a variation of the resistance R of the magnetoresistive sensor [3] with respect to the P position with a negative peak followed by a positive peak.

Claims (3)

1. Apparatus for the analysis and quantification of the concentration of analyte present in a sample using magnetoresistive sensors, characterized in that it comprises:

-

a mechanical system [1];

-

a magnetoresistive sensor [3];

-

media of magnetization [21 and 22];

where the mechanical system [1] comprises:

-

media of displacement in the Z axis [11] of the magnetoresistive sensor [3];

-

media of displacement in the X axis [10] of the strip or substrate [4];

and where these means act in such a way that the separation distance on the Z axis of the substrate [4] and the sensor magnetoresistive [3] is minimal and the position of both is coincident on the X axis. 2. Apparatus for the analysis and quantification of the concentration of analyte present in a sample using magnetoresistive sensors, characterized in that the means of displacement in the X-axis [10] of the strip or substrate [4] comprises one of the following means:

-

a wheel [12] rotating on a shaft [13];

-

a linear displacement element [14];

3. Apparatus for the analysis and quantification of the concentration of analyte present in a sample using magnetoresistive sensors, according to claims 1 and 2, characterized in that the magnetization means [21 and 22] comprise at least one of the following means:

-

two external coils [21];

-

a permanent magnet under the magnetoresistive sensor [22].