RU2478219C1 - Shaped magnetoresistive microchip of biosensor device - Google Patents

Abstract

FIELD: measurement equipment.

SUBSTANCE: shaped magnetoresistive microchip of biosensor device represents massif of magnetosensitive cells with dimensions of N times M; at that, it is made in the form of silicon crystal and includes thin-film magnetoresistors with strictly fixed orientation relative to surface and boundaries of the crystal and combined with metal layout on the crystal so that not more than N+M+3 of the output leaves it to record availability of magnetic marks in biomaterial samples.

EFFECT: increasing the quantity and enlarging the volume of samples of analysed biomaterials; reducing overall dimensions of microchips; increasing the level of cell output signal.

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Description

The invention relates to control devices for medical equipment and can be used in magnetic microbead detection devices attached to biomaterials as a result of biotinylation and hybridization processes.

A biosensor device is known that includes an array of magnetoresistive nanosensors designed to detect biomolecules containing two or more bonds of superparamagnetic nanoparticles [1].

Also known is a magnetoresistive sensor for measuring the density of magnetic nanoparticles on a microarray, in which a magnetic nanoparticle is directly or indirectly associated with the test sample [2].

The disadvantage of these matrices is the large number of conclusions and the lack of a scheme for polling array elements.

The closest in technical essence to the proposed invention is a matrix of a biosensor device based on an array of sensitive cells [3]. This device analyzes multicomponent materials to determine the individual components based on their magnetic susceptibility or dielectric constant. The device uses cells on magnetic tunnel junctions or on a giant magnetoresistive effect. The main advantage of this matrix of dimension N on M cells is the organization of the sampling scheme of magnetically sensitive elements.

The main disadvantage of this matrix is the lack of amplification of the output signal of the magnetically sensitive element.

The objective of the invention is to increase the number and increase the volume of samples of the analyzed biomaterials, reduce the overall dimensions of microchips, increase the level of the output signal of the cell.

This task is achieved by manufacturing a profiled magnetoresistive microchip of a biosensor device using integrated microsystem technology in the form of a silicon crystal containing cells from thin-film magnetoresistors located in an array of dimension N on M cells in the areas of application of biomaterial samples with a strictly fixed orientation relative to the surface and boundaries of the crystal and combined by metal wiring on the crystal so that no more than N + M + 3 pins exit from it to detect the presence of a magnet labels in samples of biomaterial.

Due to the fact that the sensitive cells are located on the same chip, there is the possibility of higher integration, which allows to increase their number and, therefore, guarantee a larger number of samples. Under the sensitive cells, on the back of the crystal, silicon regions are etched into which the analyzed biomaterial is placed, which allows increasing the sample volume without changing the crystal area. Each sensitive cell is a magnetoresistive transducer, two n-MOS transistors that provide amplification of the output signal and a diode to control the current direction when selecting a cell. The proximity of the cells to each other provides a small dispersion of the electrophysical parameters of active and passive elements. Organization of a sample of array elements by metal wiring on a chip reduces the number of outputs to N + M + 3 pieces, which ensures compactness and reliability of the circuit. By external switching with the outputs of an array of magnetically sensitive elements, by supplying a certain binary code to the N and M inputs, one of the cells is selected and the state of its two information outputs, which also belong to all other cells of the array, is interrogated, but at the time of interrogation they are turned off due to galvanic isolation through the gates of transistors and do not affect the information signal of the selected cell. Moreover, the current consumption in the array at any time does not exceed the current of one selected magnetosensitive cell.

Four thin-film magnetoresistors connected to a Wheatstone bridge are used as part of magnetosensitive cells. Bridges are combined according to nutrition, forming an array of N inputs. The common outputs from the bridges are connected to the columns of the array and comprise M inputs. The outputs of the Wheatstone bridge go to the gates of n-MOS transistors. The transistor drains are combined into two information outputs, from which the differential output signal from the load resistors is removed. The sources of the transistors are connected to the common outputs of the bridges.

The manufacturing process of a profiled microchip can be divided into four main stages. At the first stage, a membrane with a thickness of about 40 μm is formed on the back side of the substrate using anisotropic etching of silicon in 33% KOH followed by an isotropic clipping of silicon. At the second stage, according to the standard CMOS technology, a semiconductor sampling circuit is formed, consisting of n-MOS transistors with polysilicon gates. Isolation of components in the sampling scheme is carried out by Lokos thick oxide with preliminary doping of P + protection and the formation of Mesa regions to form active elements of the scheme in them. The layout of the circuit elements is carried out using Al-Si metal. Silicon oxide and nitride are used as an insulating layer. At the third stage, the formation of a magnetoresistive Ti / FeNiCo ₂₀ / Ti film. The thickness of the Ti layer is 5 ... 6 nm, the thickness of FeNiCo ₂₀ 30 ... 35 nm. Further, magnetoresistors are formed from this structure. The wiring of the magnetoresistors and switching with the sampling circuit is carried out by the second layer of metal - Al. For passivation of the elements, a precipitated layer of phosphate-silicate glass is used. At the final stage, anisotropic addition of membranes to a thickness of 5 ... 10 μm in ethylene diamine solution is performed.

Figure 1 shows a topological sketch of a profiled magnetoresistive microchip of a biosensor device with an array of sensitive elements of N rows and M columns, where

1 - magnetoresistive bridge;

2 - membrane input;

3 - contact pads.

Figure 2 shows a section of a crystal in the region of the membrane with the main structural layers, where

4 - silicon substrate;

5 - SiO ₂ ;

6 - Si ₃ N ₄ ;

7 - magnetoresistors;

8 - metal wiring;

9 - passivating dielectric.

Figure 3 shows the electrical connection diagram of magnetically sensitive cells based on the Wheatstone magnetoresistive bridges and n-MOS field-effect transistors in a matrix of dimension N by M, where

10 - inputs corresponding to line numbers (1 ... N);

11 - inputs corresponding to the column numbers (1 ... M);

12 - magnetoresistive bridges Rm _ij ;

13 - n-MOS transistors;

14 - diodes;

15 - load resistors;

16 - circuit outputs;

17 - nutrition.

A profiled magnetoresistive microchip works as follows: by external switching with N + M inputs of a biosensor device for recording magnetic marks, applying a certain binary code to them (used in digital microcircuits), only one sensitive cell is turned on, and information is read from the outputs of the circuit . This information can be converted using an analog-to-digital converter into a digital code and subsequently recorded in a memory cell corresponding to the polled sensitive cell. Submitting to the inputs all possible combinations of binary codes for polling an array of cells, the presence or absence of magnetic marks in the matrix areas of the biosensor device is sequentially determined.

Concrete example

To select an element of the array Rm _ij, it is necessary to feed logical “1” to the ith row, while all other inputs of the corresponding rows must have logical “0”, and to the jth column “0” with “1” on all other columns . Thus, in order to select the A ₁₂ element in a 3 × 3 array, it is necessary to apply a digital code of the form “100 101” to the inputs, where the first three digits determine the state of the rows, and the last ones determine the state of the columns.

The advantage of this profiled magnetoresistive microchip is that the interrogation of the array elements is carried out using a sample, in which the signal is fed directly to the gate of the n-MOS transistor. Thus, the transistors operate in the amplification mode of the output signal.

Information sources

1. US patent for 2010188075.

2. US Patent 2006128035.

3. US patent 2010103720 is a prototype.

Claims (1)

A profiled magnetoresistive microchip of a biosensor device, which is an array of magnetically sensitive cells of dimension N by M, characterized in that it is made in the form of a silicon crystal and contains thin-film magnetoresistors with a strictly fixed orientation relative to the surface and boundaries of the crystal and combined with metal wiring on the crystal so that it no more than N + M + 3 outputs are output for recording the presence of magnetic marks in samples of the biomaterial.

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