# Label-Free, Longitudinal, Multi-Metric Viability Imaging of 3D Tissue Spheroid Array

> **NIH NIH R01** · BROWN UNIVERSITY · 2022 · $343,758

## Abstract

SUMMARY
When selecting cancer therapy, physicians generally begin with first-line treatment options and monitor patient
progress on a watch-and-wait basis, following a set of guidelines based on clinical trials from a large patient
population. But this traditional method has been questioned on whether it provides individual patients with the
optimal treatment. To better find a matching treatment individually, a concept called precision cancer medicine
or personalized cancer medicine has been studied. Among other approaches, functional precision medicine
directly tests chemotherapy options on tumor cells biopsied from a patient to find the best matching treatment
for the specific patient.
This promising approach, however, has not been widely adopted by clinicians because the tumor
microenvironment in a lab differed from the one within the patient’s body, leading to inconsistent drug
responses between the sample and patient, and the quantity of biopsied cells is generally insufficient for a
reliable number of options to be tested. The first problem is being addressed by recent advances in three-
dimensional (3D) cell culture techniques, which better mimic the body’s microenvironment in a lab. But the
second problem, the limited number of testable options, is mainly due to limitations in the current assay
techniques that assess chemosensitivity in 3D culture. With most current assays, a sample can only be tested
once, and multiple drugs with different mechanisms of action cannot be simultaneously tested by a single
assay. Combined, these limitations exponentially reduce the number of testable options when involving
multiple assessment time points to design a sequential therapy or when increasing the number of drugs to test
a combination therapy.
Here, we will develop a new technique for the assessment of chemosensitivity in 3D culture, by maximizing the
potential of a label-free 3D microscopy technology, called optical coherence tomography (OCT). The majority
of prior OCT research measured only one or two types of signals and showed the signals corresponding to
only a single type of cell viability disruption process in each study. But this approach has led to a concern
about specificity (i.e., other types of processes than the one tested in the study can generate similar OCT
signals). This low specificity, along with unclear mechanisms of viability assessment, have prevented OCT
methods from being adopted for the promising concept of functional precision medicine.
Therefore, we will develop at least 18 different types of OCT signals and establish their sensitivity and
specificity to four major types of viability disruption processes. The feasibility of this approach has been
strongly supported by a pilot study where we imaged and analyzed more than 6,000 3D-cultured cell
spheroids. This R01 project will image and analyze up to 100,000+ spheroids for an unprecedentedly systemic
investigation of the comprehensive range of OCT signal types.

## Key facts

- **NIH application ID:** 10448442
- **Project number:** 5R01CA268366-02
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Jonghwan Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $343,758
- **Award type:** 5
- **Project period:** 2021-07-09 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448442

## Citation

> US National Institutes of Health, RePORTER application 10448442, Label-Free, Longitudinal, Multi-Metric Viability Imaging of 3D Tissue Spheroid Array (5R01CA268366-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10448442. Licensed CC0.

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