(Invited) In Vivo Analyte Detection Via Single-Walled Carbon Nanotube Near-Infrared Fluorescence

Abstract

Implantable optical nanosensors hold the promise of rapid, minimally-invasive longitudal monitoring of analytes in a patient or animal. Such devices will allow for informed clinical intervention based on changes in drug, biomarker, or disease state profiles. We developed implantable nanosensors based on the optical properties of single-walled carbon nanotubes (SWCNT). SWCNT fluorescence is in the ‘tissue-transparent’ near-infrared spectrum, allowing for fluorescence measurements after implantation inside an animal. Further, SWCNT fluorescence is photostable, allowing for multiple measurements over time. We engineered separate SWCNT-based sensors such that their fluorescence emission responded to various analytes, including small molecule drugs as well as protein and nucleic acid biomarkers. Each sensor device was immobilized into a semi-permeable biocompatible membrane, allowing analyte penetration but retaining SWCNT inside. We implanted each sensor device into live mice, either in the peritoneal cavity or subcutaneously, and performed whole-mouse near-infrared fluorescence imaging to ensure the stability of the membrane and sensor brightness. We used a sensor implant specific for the chemotherapeutic doxorubicin to drug monitor transport within the animal. We used sensor implants specific for the ovarian cancer protein biomarker HE4 or for individual microRNA sequences to measure exogenous or cancer-generated quantities of each biomarker in mice. We expect these implantable sensors to have potential as research tools or clinical diagnostics to monitor pharmacokinetics or locally measure disease biomarkers in real-time.