Hydrogels Holograms to Prevent Heart Attacks

Etiology is the causal study of phenomena, including diseases. Doctors sometimes have to act as detectives to identify the cause of an ailment, thus gaining more tools to halt its progression. Technology aids in anticipation through early diagnostic tools, where biomarkers come into play. These are biological indicators that reveal something about a person's health status; for example, a blood inflammation biomarker that can warn of the development of a future disease.

To further advance biomedical potential, a research team from the University of Alicante (UA) is working on a project in the field of holography and nanophotonics that, among other applications, promises rapid and precise biomarker detection. The project is named HoloNanoFab3D and is led by Augusto Beléndez Vázquez and María Inmaculada Pascual Villalobos, professors of Applied Physics and Optics at UA.

The work focuses on the development of holographic biosensors, a type of device with great potential for detecting biologically relevant molecules. "These types of sensors have numerous possible applications, such as detecting solvents and organic vapors, gases, metal ions dissolved in aqueous media, molecules, and biomolecules. One of the most interesting applications today is the detection of proteins, enzymes, and antibodies relevant for biomedical diagnosis," explains Manuel Gutiérrez, a member of the research team carrying out the project.

One of the proteins this project aims to detect is C-reactive protein, a widely recognized biomarker in the medical field that plays an important role in inflammatory processes and predicting cardiovascular diseases. "It is a protein whose levels increase in the body when inflammation occurs, so its detection allows identifying signs of such diseases or ailments, as well as cardiovascular, metabolic, and infectious ones," the researcher indicates.

These holographic biosensors consist of transmission or reflection holograms stored in photohydrogels synthesized in the laboratory. The sensor is made from a transparent hydrogel film, "a material similar to a contact lens, but not curved, rather flat," graphically explains Inmaculada Pascual. Researchers work with the hydrogel in the form of a thin sheet on the order of micrometers, generally placed on a glass support for stability.

"What we record are sinusoidal variations of the refractive index inside the photohydrogel, which translate into a holographic pattern. When the protein or another biomolecule interacts with the biosensor, the optical properties (efficiency and diffraction wavelength) of the hologram change. These changes are used as optical signal transducers and can be measured with high sensitivity," explains Inmaculada. In summary, changes in the optical properties of the hologram indicate that the substance to be detected is present. According to the UA professor, "the advantage of this system is that small concentrations produce detectable changes in the optical signal, making the device extremely sensitive."

To carry out the detection, the material used incorporates a molecular group capable of specifically recognizing the biomolecule to be detected, allowing its concentration to be quantified, for example, in a human serum sample. This way, the levels of a protein like C-reactive can be determined in a person and assess if they have inflammation or any associated process.

Similarly, this principle can be applied to detect other substances of interest in various fields such as the food, pharmaceutical, and agricultural industries. "In scientific literature, the most common until now has been the detection of glucose using this type of holographic biosensors," explains Gutiérrez. Enzymes such as amylase or protease have also been identified; the first related to pancreatic diseases, and the second involved in essential metabolic processes. "Additionally, there are biomarkers associated with heart problems that could also be detected using these systems."

The great advantage of holographic biosensors is that the device can be adapted simply by changing the receptor molecule incorporated into the hydrogel. Thus, it is possible to design specific sensors for different biomolecules and quantify their presence optically. Additionally, their fabrication is not complicated, explain the project leaders, and the production cost is relatively low compared to other types of sensors, such as electrochemical ones.

Although UA researchers have been working on holography for many years, the biomedical applications of this technology are relatively recent. Until recently, very few groups were researching in this line, although interest has grown in recent years.

Manuel points out that the innovative aspect of the work is that stable holograms have been developed in liquid media, which is a very important factor for their storage in hydrogels and subsequent use as sensors. "Traditionally, holograms were deposited on dry films that dissolved upon contact with water, so they could not be introduced into liquid solutions, which are precisely the environment where most biological samples, such as serum or blood, are found."

To make this possible, the UA team has developed a material that is not soluble in water, keeping the hologram stable even when submerged. "This advance is fundamental because until now one of the main challenges was precisely the instability of holograms in aqueous media," explains the researcher.

In fact, one of their latest works has focused on theoretically modeling and describing how the optical response of the hologram changes when submerged in a liquid, to distinguish whether the variations are due to the detection of the biomolecule or to a degradation of the material itself. "That distinction is crucial, and being able to guarantee the optical stability of the hologram represents a key step in developing reliable sensors."

Both researchers also acknowledge that the application of this technology in medical practice would be very feasible. "The material is easy to manufacture, economical, and scalable at an industrial level. Moreover, miniaturization is not a problem: the holograms are very small, approximately half a centimeter in diameter, which means that very little sample is needed to perform a detection," assures Gutiérrez.

This not only reduces the manufacturing costs of the device but also the cost of the samples used, making it a sensitive, economical, and adaptable technology with great potential for the rapid and early detection of biomarkers associated with various diseases.