Continuous steroid monitoring in interstitial fluid with wearable and nanoparticle-enhanced biosensors for improved management of adrenal disorders

• Grant number: 24/04349-2
• Support Opportunities: Research Projects - Thematic Grants
• Start date: November 01, 2024
• End date: October 31, 2028
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Madson Queiroz Almeida
• Grantee: Madson Queiroz Almeida
• Principal researcher abroad: Andreas Güntner
• Institution abroad: Swiss Federal Institute of Technology Zurich, Switzerland
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Pesquisadores principais: Berenice Bilharinho de Mendonça ; Felix Beuschlein
• Associated researchers: Helena Panteliou Lima Valassi
• Associated scholarship(s): 25/16569-0 - Extraction of cutaneous interstitial fluid using microneedle patches, BP.TT; 25/06829-4 - Determination of interstitial and serum cortisol and aldosterone concentrations by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS), BP.TT; 25/03865-0 - Validation of nanoparticle-based steroid biosensor for diagnosis of primary hyperaldosteronism., BP.PD; 25/07260-5 - Validation of a nanoparticle-based steroid biosensor for the diagnosis of adrenal insufficiency and Cushing's syndrome, BP.DD

Abstract

The adrenal steroids cortisol and aldosterone are critical components of the endocrine system. Their lack causes a life-threatening adrenal crisis, while overproduction leads to cardiovascular complications (e.g. hypertension and heart failure), metabolic disturbances, and psychological symptoms. These complications are potentially preventable if adrenal diseases are diagnosed and treated early, for which current methods often fail. More specifically, current endocrine practice relies on occasional and often random steroid measurement, but such tests have limited diagnostic and prognostic value as steroid concentrations oscillate throughout the day. This project will develop and clinically validate sensing solutions for dynamic steroid tracking over prolonged periods at high patient comfort. First, we will establish interstitial aldosterone and cortisol as reliable predictors of steroid excess or deficiency by comparative measurements to blood serum by liquid chromatography-mass spectrometry (LC-MS/MS) to close critical gaps in existing data sets. In parallel, biocompatible hollow microneedle platforms will be developed by 3D printing and microfabrication enabling continuous and minimally invasive interstitial fluid extraction, as supported by preliminary data. Equipping these platforms with porous films of aptamer-functionalized transducer nanoparticles will yield specific steroid quantification down to relevant pico-molar concentration. For rapid and reversible sensing, a novel concept of light-activated thermoplasmonic analyte release will be explored. The resulting wearable prototypes will be tested during 48h in appropriate cohorts of healthy individuals and patients with adrenal disease (cortisol and/or aldosterone disorders), as estimated by power calculation. This project will advance endocrinology from single timepoint to dynamic assessment by unleashing synergies in clinical and engineering research between Univ. Sao Paulo Medical School and ETH Zürich. (AU)