Biosensor Detects Depression, Schizophrenia Protein

Fundação de Amparo à Pesquisa do Estado de São Paulo

Brazilian researchers have developed a low-cost, portable biosensor that can quickly identify a protein whose altered levels are associated with psychiatric disorders, such as depression, schizophrenia, and bipolar disorder. When it becomes commercially available in the future, it may contribute to early detection, which is essential for treating and monitoring patients' clinical conditions.

The biosensor is the result of a partnership between researchers at the University of São Paulo (USP) and Embrapa Instrumentação, a decentralized unit of the Brazilian Agricultural Research Corporation (Embrapa). It consists of a flexible strip with electrodes that, when integrated with a portable analyzer, evaluates drops of human saliva. In less than three minutes, the biosensor provides the concentration of BDNF (brain-derived neurotrophic factor), a protein crucial for the growth and maintenance of neurons and the development of brain functions, including learning and memory.

The research, published in ACS Polymers Au, shows that the device can reliably measure extremely low concentrations of the protein in a wide range of saliva (from 10⁻²⁰ to 10⁻¹⁰ grams per milliliter), down to minimal amounts that are still detectable (1.0 × 10⁻²⁰ grams per milliliter).

The biosensor has an estimated cost of US$2.19 per unit — less than R$12.00 at the current exchange rate — and long-term storage capacity. According to the scientists, the next step is to obtain the patent.

"There are few sensors that perform this type of analysis, and ours was the one that performed best. It detected a wide range of concentrations, which is a very good result from a clinical point of view. When protein levels are very low, it can serve as a warning sign for diseases and psychiatric disorders. On the other hand, by being able to signal an increase in BDNF, it contributes as a tool to monitor the patient's progress according to the treatment," explains Paulo Augusto Raymundo Pereira , a researcher at the São Carlos Institute of Physics (IFSC-USP) and corresponding author of the article, in an interview with Agência FAPESP.

Pereira, who has experience in chemistry and biotechnology, has been working with flexible sensors and electrochemical biosensors. Last year, he was one of the authors of an article in the Chemical Engineering Journal that presented the results of a portable sensor for urine self-testing aimed at detecting markers of diseases such as gout and Parkinson's (read more at https://agencia.fapesp.br/51727 ).

Link to disorders

Scientific literature shows that low levels of BDNF are one of the factors involved in some neurological and psychiatric disorders associated with cognitive decline. Depression is one such disorder. The effect of the protein is restored by antidepressants. Healthy individuals have BDNF levels above 20 nanograms per milliliter (ng/mL), whereas people with major depressive disorder (MDD) have levels below 10 or 12 ng/mL.

According to data from the World Health Organization (WHO), more than 1 billion people live with mental disorders, with anxiety and depression being the most prevalent conditions. According to the organization's reports, including the Mental Health Atlas 2024 , these disorders have increased in prevalence in all countries, affecting people of all ages and income levels.

Between 2022 and 2024, worker absences due to mental health issues in Brazil increased by 134%. According to the Occupational Safety and Health Observatory , these absences rose from 201,000 to 472,000 and were caused by episodes of depression, anxiety, and recurrent depression.

Pereira adds, "The increase in cases of mental disorders and the consequent rise in the use of medication, especially after the COVID-19 pandemic, motivated us to work on this issue and seek alternatives." Pereira has the support of FAPESP through scholarships ( 16/01919-6 , 23/09685-8 , and 22/02164-0 ).

The device

The researchers developed a flexible strip screen-printed on a polyester film substrate with three electrodes: one functionalized working electrode, one pure carbon auxiliary electrode, and one silver reference electrode.

The working electrode was modified with carbon nanospheres. It received a layer of two chemical compounds – polyethyleneimine and glutaraldehyde – to increase sensitivity and act as a matrix to immobilize the BDNF-specific capture antibody (anti-BDNF). To prevent other types of interaction, a reactive layer of ethanolamine was added.

BDNF detection is based on the formation of antibody-antigen immunocomplexes, which increase resistance to electron transfer on the sensor surface. This growth is captured by electrochemical impedance spectroscopy, a technique used to study processes that occur at the interface between an electrode and a solution.

The results can be displayed in real time on a mobile device (smartphone) via wireless communication (Bluetooth).

The current techniques used to analyze BDNF levels include the enzyme-linked immunosorbent assay (ELISA), electrochemiluminescence, fluorescence, and high-performance liquid chromatography (HPLC). These techniques require time, large sample volumes, and specialized laboratories.

"We're moving toward personalized medicine, in which treatments will be increasingly tailored to each individual. In the case of the biosensor, it can be optimized to suit different profiles," says the researcher.

FAPESP also supported the study through the Thematic Project " Towards the Convergence of Technologies: From Sensors and Biosensors to Information Visualization and Machine Learning for Data Analysis in Clinical Diagnosis ", as well as two other projects ( 23/07686-7 and 20/09587-8 ).

The team includes the following researchers: Nathalia Gomes , Marcelo Luiz Calegaro , Luiz Henrique Capparelli Mattoso , Sergio Antonio Spinola Machado , and Osvaldo de Oliveira Junior .

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe .

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