Title: A 25 micron-thin microscope for imaging upconverting nanoparticles with NIR-I and NIR-II illumination

Abstract

Rationale: Intraoperative visualization in small surgical cavities and hard-to-access areas are essential requirements for modern, minimally invasive surgeries and demand significant miniaturization. However, current optical imagers require multiple hard-to-miniaturize components including lenses, filters and optical fibers. These components restrict both the form-factor and maneuverability of these imagers, and imagers largely remain stand-alone devices with centimeter-scale dimensions. Methods: We have engineered INSITE (Immunotargeted Nanoparticle Single-Chip Imaging Technology), which integrates the unique optical properties of lanthanide-based alloyed upconverting nanoparticles (aUCNPs) with the time-resolved imaging of a 25-micron thin CMOS-based (complementary metal oxide semiconductor) imager. We have synthesized core/shell aUCNPs of different compositions and imaged their visible emission with INSITE under either NIR-I and NIR-II photoexcitation. We characterized aUCNP imaging with INSITE across both varying aUCNP composition and 980 nm and 1550 nm excitation wavelengths. To demonstrate clinical experimental validity, we also conducted an intratumoral injection into LNCaP prostate tumors in a male nude mouse that was subsequently excised and imaged with INSITE. Results: Under the low illumination fluences compatible with live animal imaging, we measure aUCNP radiative lifetimes of 600 μs - 1.3 ms, which provides strong signal for time-resolved INSITE imaging. Core/shell NaEr_0.6Yb_0.4F₄ aUCNPs show the highest INSITE signal when illuminatedmore » at either 980 nm or 1550 nm, with signal from NIR-I excitation about an order of magnitude brighter than from NIR-II excitation. The 55 μm spatial resolution achievable with this approach is demonstrated through imaging of aUCNPs in PDMS (polydimethylsiloxane) micro-wells, showing resolution of micrometer-scale targets with single-pixel precision. INSITE imaging of intratumoral NaEr_0.8Yb_0.2F₄ aUCNPs shows a signal-to-background ratio of 9, limited only by photodiode dark current and electronic noise. Conclusion: This work demonstrates INSITE imaging of aUCNPs in tumors, achieving an imaging platform that is thinned to just a 25 μm-thin, planar form-factor, with both NIR-I and NIR-II excitation. Based on a highly paralleled array structure INSITE is scalable, enabling direct coupling with a wide array of surgical and robotic tools for seamless integration with tissue actuation, resection or ablation.« less

Authors:

Najafiaghdam, Hossein ^[1]; Papageorgiou, Efthymios ^[1]; Torquato, Nicole A. ^[2]; Tian, Bining ^[2]; Cohen, Bruce E. ^[2]; Anwar, Mekhail ^[3]

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+ Show Author Affiliations

1. Univ. of California, Berkeley, CA (United States)
2. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
3. Univ. of California, San Francisco, CA (United States)

Publication Date:

Fri Oct 18 00:00:00 EDT 2019

Research Org.:

Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Org.:

USDOE Office of Science (SC); National Institutes of Health (NIH)

OSTI Identifier:

1599788

Grant/Contract Number:  

AC02-05CH11231; R21EB027238

Resource Type:

Accepted Manuscript

Journal Name:

Theranostics

Additional Journal Information:

Journal Volume: 9; Journal Issue: 26; Journal ID: ISSN 1838-7640

Publisher:

Ivyspring

Country of Publication:

United States

Language:

English

Subject:

62 RADIOLOGY AND NUCLEAR MEDICINE; intraoperative imaging; upconverting nanoparticle; time-resolved imaging; NIR excitation