# Multiplexed Imaging in the Near Infrared with Indium Phosphide Quantum Shells

> **NIH NIH R01** · NORTHEASTERN UNIVERSITY · 2022 · $440,183

## Abstract

Project Summary/Abstract
Fluorescence has significant potential for biomedical imaging applications because of the relatively low cost of
imaging equipment, the nominal toxicity of non-ionizing radiation (i.e., light), the potential for molecular imaging
using target-specific contrast agents, and the prospect of multiplexed imaging using discretely colored
fluorophores. Molecules common in biological tissues including lipids, water, and hemoglobin scatter and absorb
light, rendering tissue opaque to visible wavelengths, but longer, near infrared (NIR) wavelengths penetrate
deeper, giving us an optical window into the body. To see inside a tissue, we require bright, photostable, highly
absorbing, NIR fluorophores. Despite exceptional results in vitro, we can improve on the in vivo performance of
organic dyes, fluorescent proteins, and traditional semiconductor quantum dots (QDs), which are typically dim,
toxic, not red enough, or all of the above. We have created a material that literally flips a quantum dot inside out
to make a quantum shell (QS) comprised of non-toxic elements (In, P, Se, Zn, S) that is tunable from 500 – 900
nm. Because InP absorbs more efficiently than CdSe, these materials are brighter than previous materials with
a smaller size, while emitting in the NIR and reducing toxicity. We propose a technology development plan that
would enable us to refine the structural and optical properties of these particles to generate a brightness-matched
palette of fluorophores to enable multiplexing in deep tissue. We will deploy these particles in widefield imaging
and multiphoton microscopy (MPM) experiments to first objectively quantify and then demonstrate the optical
superiority of these probes. After evaluating the in vitro and in vivo biocompatibility of various formulations of
water-soluble QSs, we will use targeted and untargeted QSs together for dual probe imaging of cell surface
biomarkers to selectively highlight a xenograft tumor. In addition to widefield imaging, we will objectively evaluate
the MPM contrast of the QSs. The exceptionally high absorptivity of the particles ensures high two- and three-
photon action cross-sections. We will quantitatively compare the brightness and tissue penetration depth of the
InP QSs against other red and NIR fluorophores. Synthetic iterations to the particles will use the unique particle
geometry to generate QSs with varying emission colors, but the same brightness. We will compare zwitterionic
coatings to our benchmark lipid-PEG coating to try to enhance imaging contrast through longer circulation time
and more efficient targeting. The success of this project will yield a rainbow of non-toxic, NIR fluorophores that
can be used collectively could transform preclinical molecular imaging.

## Key facts

- **NIH application ID:** 10682976
- **Project number:** 7R01GM129437-04
- **Recipient organization:** NORTHEASTERN UNIVERSITY
- **Principal Investigator:** Allison Marie Dennis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $440,183
- **Award type:** 7
- **Project period:** 2019-09-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10682976

## Citation

> US National Institutes of Health, RePORTER application 10682976, Multiplexed Imaging in the Near Infrared with Indium Phosphide Quantum Shells (7R01GM129437-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10682976. Licensed CC0.

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