Design of a single particle-interferometric reflectance imaging sensor adipo-chip for obesity biomarker screening

In light of the obesity pandemic, there is an increasing imperative to identify obesity phenotypes that encompass factors such as adipose tissue distribution, inflammation, and insulin sensitivity, to devise tailored therapeutic strategies. Within this context, extracellular vesicles (EVs) have emerged as promising reservoirs of biomarkers. However, the inherent technical challenges associated with their isolation and analysis necessitate the development of precise, high-throughput technologies to facilitate their integration into clinical settings. The single-particle interferometric reflectance imaging sensor (SP-IRIS) has emerged as a valuable tool that enables the analysis of biomarkers in individual EVs without the need for prior purification. The fundamental principle of SP-IRIS involves the capture of EVs using functionalized chips with capture antibodies targeting standard exosomal tetraspanins, with the option of employing custom antibodies to capture cell- or tissue-specific EVs. Herein, we describe, for the first time, the design and validation of an SP-IRIS chip functionalized with two capture antibodies to assess adipose-specific (adipo-chip) secreted vesicles for biomarker assessment. Using this approach, we demonstrate that the designed adipo-chip captures EVs directly secreted by the whole adipose tissue of patients with obesity undergoing bariatric surgery, allowing the quantification of up to four previously described adipose EV-biomarkers. Thus, we demonstrate for the first time the capacity of the adipo-chip to enrich the capture of adipose-secreted EVs, enabling the detection of changes in described biomarkers with potential applications in clinical settings through liquid biopsy at the circulating level.