Introduction

Health relevant information is coded in circulating signatures or biomarkers, such as the secretome, exosomes, nucleic acids, bacteria, and other markers for health.\cite{HayBurgess2006,Giljohann2009,Yuan2019} The collection and analysis of such signatures can serve as an early sign of disease initiation and its progression through repeated sampling.\cite{Sinawang_2021,Smith2002,Ransohoff2004,Ozen2020} Nevertheless, it remains a challenge to isolate or sample biomarkers from regions of the body with limited accessibility, such as the gastrointestinal tract, which is more than 30 feet in length in total.\cite{Cummins2017,Badreddine2008}  To gain access to these challenging locations, invasive medical procedures, such as surgery, biopsies, and colonoscopies, are required to extract information, limiting the repeatability of such measurements.\cite{Washabau2010,Lhewa2012,Ciuti2020} These techniques involve trained practitioners, expensive instruments, and specialized facilities, making them hard to expand to a large population. On the other hand, minimally invasive approaches can also be used for sampling biomarkers.\cite{Tang2020} For instance, liquid biopsy is a standard approach to obtain a snapshot of the signature pool from biofluids (blood, urine, or stool samples).\cite{Saini2018,Wu2020}  Although useful, liquid biopsy frequently provides indirect data that is averaged across the sample that is not specific to a particular region of the body. Smart pills have been deployed as a method to sample cavities inside the body.\cite{Yim2014,Cummins2021,Mandsberg2020,Iddan2000,Min2019,Steiger2018} For instance, microfluidic chips,\cite{Mimee2018,Qiao2016,Nemiroski2015} osmotic gradients,\cite{RezaeiNejad2019} and passive absorption\cite{Waimin2020,Rios-Morales2021,Chen2020} have been deployed to collect biomarkers in the GI tract. Previous pill-based approaches are designed to focus on imaging of the GI tract\cite{Iddan2000} or have active electrical components,\cite{Schostek2016} and here we focus on capturing low abundance biomarkers via a simple. The ability to isolate biomarkers within localized environments and specificity could help discover novel early disease signals and monitor health status by allowing the generation of comprehensive datasets encompassing the shift from healthy to disease states and vice versa.
Herein, the use of a robotic pill platform is presented for enhanced collection and isolation of biomarkers. The robotic pill comprises three modular compartments with spatially resolved zones for different features, including sampling, delayed opening of the sampling gate, locomotion , and  retention of the robotic pill in predetermined regions. The integration of these capabilities would assist in prolonged sampling at a target site, resulting in the capture of a sufficient quantity of GI biomarkers required to provide a sampling. The proposed approach could eventually result in a complementary sampling tool for routine gastric measurements in the clinical practice towards disease early detection and monitoring.