Abstract
Molecular optical imaging is a widespread technique for interrogating molecular events in living subjects. However, current approaches preclude long-term, continuous measurements in awake, mobile subjects, a strategy crucial in several medical conditions. Consequently, we designed a novel, lightweight miniature biosensor for in vivo continuous optical sensing. The biosensor contains an enclosed vertical-cavity surface-emitting semiconductor laser and an adjacent pair of near-infrared optically filtered detectors. We employed two sensors (dual sensing) to simultaneously interrogate normal and diseased tumor sites. Having established the sensors are precise with phantom and in vivo studies, we performed dual, continuous sensing in tumor (human glioblastoma cells) bearing mice using the targeted molecular probe cRGD-Cy5.5, which targets αVβ3 cell surface integrins in both tumor neovasculature and tumor. The sensors capture the dynamic time-activity curve of the targeted molecular probe. The average tumor to background ratio after signal calibration for cRGD-Cy5.5 injection is approximately 2.43 ± 0.95 at 1 h and 3.64 ± 1.38 at 2 h (N = 5 mice), consistent with data obtained with a cooled charge coupled device camera. We conclude that our novel, portable, precise biosensor can be used to evaluate both kinetics and steady state levels of molecular probes in various disease applications.
| Original language | English |
|---|---|
| Article number | 117004 |
| Journal | Journal of Biomedical Optics |
| Volume | 17 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2012 |
Bibliographical note
Funding Information:The authors are grateful for the helpful discussions and assistance during experiments with Zachary Walls during the early phases of this project. The authors want to thank Anthony Kim (Ontario Cancer Institute–Princess Margaret Hospital). The authors also wish to thank Mary Hibbs-Brenner and Klein Johnson from Vixar, Inc. for assistance in epitaxial growth; Choma Technology Corp. for its generous donation of emission filter coatings; and Breault Research Organization for an educational license of ASAP. We thank Brian Wilson, of Princess Margaret Hospital, and Elizabeth Monroe, of University of Toronto, for making the tissue phantom and measuring its properties. Fabrication of devices was carried out in the Stanford Nanofabrication Facility (SNF). This work was supported in part through an Interdisciplinary Translational Research Program (ITRP) grant through the Stanford University Beckman Center for Molecular and Genetic Medicine (SSG & JSH) and from the National Cancer Institute ICMIC P50 CA114747 (SSG). It is also supported in part through the University of Toronto departmental start-up funds to OL, the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant RGPIN-355623-08 and by the Networks of Centres of Excellence of Canada, Canadian Institute for Photonic Innovations (CIPI). Funding for materials was provided though the Photonics Technology Access Program (PTAP) sponsored by NSF and DARPA-MTO. NP was supported by NIH T32 Training grant and Stanford Dean’s Fellowship. TDO acknowledges graduate support from a National Defense Science and Engineering Graduate (NDSEG) fellowship, the U.S. Department of Homeland Security, and an SPIE scholarship. Dr. S. Cho is supported by the National Research Foundation of Korea Grant funded by the Korean government [NRF-2011-357-D00155].
Keywords
- angiogenesis
- continuous sensing
- molecular imaging
- molecular probe kinetics
- molecular probes
- noninvasive sensing
- semiconductor sensors
- vertical-cavity surface-emitting laser
