title: Real-time, continuous, fluorescence sensing in a freely-moving subject with an implanted hybrid VCSEL/CMOS biosensor.
abstract: Performance improvements in instrumentation for optical imaging have contributed greatly to molecular imaging in living subjects. In order to advance molecular imaging in freely moving, untethered subjects, we designed a miniature vertical-cavity surface-emitting laser (VCSEL)-based biosensor measuring 1cm(3) and weighing 0.7g that accurately detects both fluorophore and tumor-targeted molecular probes in small animals. We integrated a critical enabling component, a complementary metal-oxide semiconductor (CMOS) read-out integrated circuit, which digitized the fluorescence signal to achieve autofluorescence-limited sensitivity. After surgical implantation of the lightweight sensor for two weeks, we obtained continuous and dynamic fluorophore measurements while the subject was un-anesthetized and mobile. The technology demonstrated here represents a critical step in the path toward untethered optical sensing using an integrated optoelectronic implant.
authors.affiliation: Department of Electrical Engineering, Stanford University, 420 Via Palou, Stanford, CA 94305-4075, USA ; These authors contributed equally to this work.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: O'Sullivan
authors.forename: Roxana T
authors.initials: RT
authors.lastname: Heitz
authors.forename: Natesh
authors.initials: N
authors.lastname: Parashurama
authors.forename: David B
authors.initials: DB
authors.lastname: Barkin
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Wooley
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
authors.forename: James S
authors.initials: JS
authors.lastname: Harris
authors.forename: Ofer
authors.initials: O
authors.lastname: Levi
keywords: (130.5990) Semiconductors; (130.6010) Sensors; (140.2020) Diode lasers; (170.3890) Medical optics instrumentation; (230.5160) Photodetectors