**4. Biocompatibility**

In the previous paragraphs it has been shown that the different materials that are used as sensors should meet different requirements from the point of view of their magnetic properties: the optimal response of the device could be achieved with the softest, the hardest or the most magnetostrictive material. It depends on the application. It should be remarked that to assure a long-term working life-time of the device, it is necessary to look for a material with specific mechanical properties (González-Carrasco, 2009), as for example high fatigue resistance for the cardiac valve sensor. In the particular case of the implantable devices, it is evident that there is a decisive requirement that is more important than all those physical properties. This is, that the device cannot harm the patient, so the system must be biocompatible. The definition of the term Biocompatibility says: "Biocompatibility refers to the ability of a material to perform with an appropriate host response in a specific situation" (Williams, 1987).

Bearing in mind, that the human organism can be considered, in a very schematic way, as an assemblage of different tissues and fluids with different properties (biological, physical and chemical) as well as being a very aggressive medium against exogenous elements, it is easy to infer that the problem of the biocompatibility of the materials is very complex and should be studied for each specific application (Williams, 2008). In general, biocompatibility studies usually begin with in vitro tests (i.e. cell viability, preferably with cells of the host tissue/organ, and an endless quantity of trials concerned with the promotion or inhibition of biological process) followed by in vivo trials on experimental animals (Ratner et al., 2004).

Biomaterials, understood as materials that are biocompatible, can be classified in accordance with different parameters, for example their nature (metal, ceramic, polymer...), their application (bone, vascular, eye...) or their size. For reviewing the state of the

Fig. 12. Nanoparticles (black spots) inside the cell after apopthosis (White holes)

These results show that perovskite nanoparticles have a high potential for cancer cell hyperthermia, working as smart mediators for self controlled heating of tumours, where the heating source is switched off when the local temperature of the tumour reaches the

In the previous paragraphs it has been shown that the different materials that are used as sensors should meet different requirements from the point of view of their magnetic properties: the optimal response of the device could be achieved with the softest, the hardest or the most magnetostrictive material. It depends on the application. It should be remarked that to assure a long-term working life-time of the device, it is necessary to look for a material with specific mechanical properties (González-Carrasco, 2009), as for example high fatigue resistance for the cardiac valve sensor. In the particular case of the implantable devices, it is evident that there is a decisive requirement that is more important than all those physical properties. This is, that the device cannot harm the patient, so the system must be biocompatible. The definition of the term Biocompatibility says: "Biocompatibility refers to the ability of a material to perform with an appropriate host response in a specific

Bearing in mind, that the human organism can be considered, in a very schematic way, as an assemblage of different tissues and fluids with different properties (biological, physical and chemical) as well as being a very aggressive medium against exogenous elements, it is easy to infer that the problem of the biocompatibility of the materials is very complex and should be studied for each specific application (Williams, 2008). In general, biocompatibility studies usually begin with in vitro tests (i.e. cell viability, preferably with cells of the host tissue/organ, and an endless quantity of trials concerned with the promotion or inhibition of biological process) followed by in vivo trials on experimental animals (Ratner et al., 2004). Biomaterials, understood as materials that are biocompatible, can be classified in accordance with different parameters, for example their nature (metal, ceramic, polymer...), their application (bone, vascular, eye...) or their size. For reviewing the state of the

(Villanueva, 2010)

desired value.

**4. Biocompatibility** 

situation" (Williams, 1987).

biocompatibility of magnetic materials, this last option is more appropriate. Two large groups of materials can be distinguished: those used as bulk materials and the micro/nanoparticles.

On the one hand, among the widely established bulk biomaterials (titanium alloys, cobaltchromium alloys, noble metals, Nitinol, austenitic stainless steel, alumina, calcium phosphates, carbon and polymers like UHMW polyethylene, PMMA or silicones) there are none with ferromagnetic properties. Regarding the metallic materials (excepting the noble metals, which are not ferromagnetic) only those that develop a well attached surface oxide layer usually present a good response to corrosion. In fact, if Chromium is added above 12% weight to Fe or Co the alloys become stainless. The stainless steels used for medical applications (316L and 304L) also incorporate Ni, among other elements, in their composition, which improves their corrosion resistance and stabilizes the face centred cubic structure. This latter fact explains their paramagnetic character.

In general, it could be said that most the ferromagnetic materials are not biocompatible or their biocompatibility is not known. Very few papers on the biocompatibility of magnetic materials can be found. Even fewer can be found on cells. Most of them are corrosion studies done with liquids that simulate the pH of different biological mediums. Magnets have attracted interest in medicine (Riley at al., 2002). In particular, rare earth magnets have been investigated in the field of dentistry to push or pull teeth or as prostheses retention systems (Noar et al., 1999). They show bad corrosion resistance and have been used embedded in different polymeric materials or with Ti coating.

Studies on Fe-Co alloys and magnetostrictive NiMnGa and Terfenol\_D show poor cell viability, excepting the last one that presents high corrosion (Pouponneau et al. 2006). However the system Co-Pt and Fe-Pt show better corrosion response (Yiu et al. 2004)). At research level, the Fe based alloy PM2000 shows good corrosion behaviour and cell viability together with a significant saturation magnetization, especially when coated with alumina by thermal oxidation (Flores et al., 2004).

The surface is where the first contact between the material and the biological entity takes place. This is why surface biomaterials are being researched in depth, while surface modification is one of the most widely used strategies for improving biomaterial properties.

In the case where a magnetic feature can only be achieved with a material that is not biocompatible the simplest solution is to encapsulate it or to coat it with a biocompatible material. Anyway, as coatings also present their own problems (adherence, thickness,...), it would be very interesting to investigate and to develop biomaterials with good magnetic properties.

On the other hand, there already exist some nanoparticles commercially used as contrast agents in imaging diagnostic techniques or drug targeting and magnetic separation applications, like the Iron Oxide or the Gd, because of their magnetic properties. However, an enormous effort is being made to develop biocompatible magnetic nanoparticles for their application in biomedicine due to the attractive possibilities that they offer (Pankhurst, 2003) as hyperthermia agents for coadyuvant cancer treatment, drug delivery systems, as well as for the previously mentioned reasons.

Magnetic Sensors for Biomedical Applications 147

limitations increase by up to 33%, which means severe restrictions on mobility. In these advanced stages of the disease, the symptoms limit the patient's mobility very severely and

The goal of this research would be to exploit the possibilities offered by telemedicine and remote control for improving the assistance, monitoring and quality of life in MS patients, in

Autonomic alteration: cardiac rhythm, blood-pressure variations, gastrointestinal

Clinical evolution monitoring ( search of image subrogated markers obtained by

These neurological requirements scenarios could be analyzed at a distance by using the appropriate sensors (with calls and alerts), so that the neurologist would be able to treat the patient without the patient needing to be in presence of the physician and so avoiding

It is not possible in the space available to offer an exhaustive overview of the applications of magnetic sensors in the field of medicine. We have limited ourselves to presenting just some particular works, that we have recently developed, some that are currently being developed

It seems obvious that the development of magnetic sensors and actuators is generally linked to the development of magnetic materials. Furthermore, it could be said that the development of our technological civilization is linked to the development of magnetic materials. If this assertion sounds too exaggerated, please imagine the consequences of the disappearance of the silicon steel sheet and with it all the electric motors and transformers. Or just think about the permanent magnets inside all mobile phones, or the magnetic

mobility alterations and sphincters control (anal and urethral)

Development of complications derived from the physical condition

drastically affect the quality of life and autonomy of these patients.

the advanced stages and with very limited mobility.

It would be focused on three aspects:

 Symptoms monitoring: Spasticity Dysphagia Pain

> Position Sleep quality

 Decubitus ulcers Urine infection

 Walk monitoring Upper limbs monitoring Mental function monitoring Autonomic state monitoring

and some that are still in the future.

**6. Conclusion** 

Respiratory infection (aspiration)

Position alteration (orthopaedic malformation)

complications that would decrease the quality of life.

periodical and quantifiable Magnetic Resonance studies)

The problem of the toxicity of nanoparticles goes further than in vitro trials with cells, (it can be really complex) (Lewinsky, 2008). In fact this kind of material has other problems when used for long term devices. For example, once their behaviour with cells has been tested, it is essential to understand their survival in the body. Do the macrophages detect them too soon or on the contrary, do the nanoparticles tend to accumulate in some important organ such as the liver or brain? (Hoet et al., 2004). Nanoparticles are frequently coated with different organic or inorganic materials (as dextran (Lacava, 2001) or silica (Villanueva, 2010)). Sometimes this is done to make them biocompatible, sometimes to obtain an appropriate dispersion and sometimes to functionalize them.
