Biosensor, method of forming and use

Details Biosensor, method of forming and use Biosensor, method of forming and use

1999-10-15

2001-12-25

Noori, Max (Department: 2855)

Measuring and testing

Specimen stress or strain, or testing by stress or strain...

Specified electrical sensor or system

C427S577000

Reexamination Certificate

active

06332363

ABSTRACT:

This invention relates to improvements in or relating to sensors, and in particular to those sensors termed biosensors, ie devices for the analysis and investigation of biological or biologically active species such as antigens and antibodies, enzymes, substrates, proteins, haptens, whole cells and cellular fragments and nucleic acids.
Many devices for the automatic determination of biochemical analytes in solution have been proposed in recent years. Typically, such devices (biosensors) include a sensitised coating layer which is located in the evanescent region of a resonant field. Typically, the coating layer comprises a layer of biological molecules chemically linked to the surface, either directly or via an intermediate linking molecule, or immobilised within a matrix of, for instance, hydrogel molecules bound to the surface.
Detection of the molecule under investigation (“the analyte”) typically utilizes optical techniques such as, for example, surface plasmon resonance (SPR) or frustrated total reflection (FTR), and is based on changes in the thickness and/or refractive index of the coating layer resulting from interaction of that layer with the analyte. This causes a change in the properties of the sensor, eg a change in the angular position of the resonance. Other forms of biosensor include devices with semiconducting surfaces, the electrical properties of the device being monitored and, notably, acoustic devices in which changes in surface bulk loading are detected.
Since the measurements made using biosensors of the types described are essentially measurements of events or changes occurring at the sensitised surface of the device, it is critical to the accuracy and reliability of the measurements that the integrity of that surface is maintained. In an SPR or FTR sensor, for example, the device monitors the resonating properties of a structure the natural frequency of which is altered as changes take place at its surface. If the sample can alter the bulk of the structure in a non-specific manner then the integrity of the measurement is destroyed. In practice, maintenance of surface integrity may not be achieved and this gives rise to errors in the experimental results and/or greatly limits the useful life of the sensor devices. For example, repeated application of reagents to the surface (as is inevitable in a series of measurements) may result in attrition of the surface, with a consequent unpredictable change in properties. The surface may be somewhat porous, with the result that reagents may be absorbed, again changing the properties of the device. Chemical linkages between the surface and the molecules immobilized on it may also become broken in the course of chemical treatment.
There has now been devised an improvement to sensors of the kind generally described above which overcomes or substantially mitigates the disadvantages of the prior art.
According to the invention, a sensor device has a sensing surface on which, in use, first molecules are immobilized, the first molecules being capable of interaction with second molecules which may be present in a sample of fluid applied to the sensing surface, such interaction resulting in a measurable change of some physical property of the sensor device, wherein the sensing surface is coated with a layer of diamond-like carbon.
The sensor device according to the invention is advantageous primarily in that the layer of diamond-like carbon (DLC) protects and preserves the integrity of the sensing surface. The device is impervious to the reagents and fluids with which it is, in use, contacted. Problems of attrition of the surface and porosity are reduced, and linkages of the first molecules to the surface are more stable. Furthermore, and particularly importantly, by appropriate control of the composition of the diamond-like carbon layer (as described below) a wide variety of functionalities may be incorporated into it in a thickness-dependent manner.
DLC is a dense, partially sp
3
bonded form of amorphous carbon. Its atomic structure consists of a network of sp
3
and sp
2
sites, the connectivity of the sp
3
sites controlling the mechanical properties of the material. DLC is conventionally used as a hard coating material, ie to confer “diamond-like” properties such as mechanical hardness and low friction on substrate materials. Since the purpose of the DLC layer used in the present invention is not primarily to confer a high degree of hardness on the active surface of the sensor device, the layer may have a hardness which is considerably less than that achieved in conventional applications of DLC.
The DLC layer may be formed by plasma deposition or chemical vapour deposition techniques. Typically, monomeric starting materials in the gas phase are introduced into a vacuum chamber containing a pair of electrodes. The device to be coated is supported in the chamber on one of the electrodes and a radiofrequency or microwave discharge is applied.
Generally, the starting material includes a hydrocarbon, most preferably methane. However, in principle any suitable hydrocarbon may be used, eg ethylene, acetylene, ethane, or aromatic species such as toluene and styrene. Mixtures of starting materials may be used to give desired physical properties.
It may also be desirable to incorporate other chemical functionality in the DLC layer. For instance, by introducing CH
3
NH
2
gas in the final stages of the deposition, a DLC layer may be formed with a surface which includes amino groups. Such groups may be useful for the direct immobilization of biomolecules. Similarly, inclusion of carboxylate-containing species in the vapour may give rise to a surface with carboxylate functionality. The starting materials may also include small quantities of gases such as argon, neon, nitrogen, oxygen or helium. Appropriate combinations of starting materials may also be used to produce DLC layers having particularly hydrophobic or hydrophilic properties.
Because the polymerisation reaction is essentially simple, a high degree of control can be exercised over the chemical and physical nature of the DLC layer, enabling the properties of that layer to be easily tailored to the particular application for which the sensor device is intended. One physical parameter which is important is the density of the DLC layer, which is determined largely by the proportion of sp
3
to sp
2
hybridized carbon. For optical sensors, a dense DLC layer is desirable to minimise the thickness of the DLC layer necessary to provide the necessary degree of protection without adversely affecting the optical properties of the sensor. The density (and thickness) of the DLC layer may be less important, or not at all important, for non-optical sensors.
The DLC layer should have a thickness which is sufficient to confer the desired degree of protection on the sensing surface of the sensor device. The thickness of the DLC layer can be controlled by appropriate choice of the operating parameters of the deposition apparatus, notably the period for which the deposition is carried out. In general, the thickness should be no greater than the minimum required, so as to avoid any possible deleterious effects of the DLC layer on the properties, eg the sensitivity, of the sensor device. Typically, the DLC layer will have a thickness of less than 100 nm, more preferably less than 50 nm, and particularly less than 20 nm. A thickness of greater than 1 nm, and generally greater than 5 nm will normally be required. The thickness is most preferably of the order of 10 nm.
The DLC layer may be applied directly to the surface of the sensor device which it is desired to protect. However, since the DLC layer may not adhere sufficiently well to the material of that surface, it may be necessary to apply first a thin layer of another material to which the DLC layer will adhere well.
The sensor device according to the invention may be of any type, eg an optical sensor or any other formn of sensor in which changes at the sensing surface result in a measurable change of physical property. One preferred for

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