A Versatile Optical Frontend for Multicolor Fluorescence Imaging with Miniaturized Lensless Sensors

TL;DR

This paper presents a flexible optical frontend for lensless fluorescence imaging that improves sensitivity and enables multicolor imaging, advancing compact, low-cost diagnostic devices.

Contribution

It introduces a fiber optic plate-based technique to enhance angle-insensitivity and optimize resolution in lensless fluorescence sensors, with detailed analysis and experimental validation.

Findings

High-NA design increases fluorescence sensitivity by 59 times.

Low-NA design enables three-color fluorescence imaging.

Optimized filters on both sides of FOP improve angle-insensitivity.

Abstract

Lensless imaging enables exceptionally compact fluorescence sensors, advancing applications in \textit{in vivo} imaging and low-cost, point-of-care diagnostics. These sensors require a filter to block the excitation light while passing fluorescent emissions. However, conventional thin-film interference filters are sensitive to angle of incidence (AOI), complicating their use in lensless systems. Here we thoroughly analyze and optimize a technique using a fiber optic plate (FOP) to absorb off-axis light that would bleed through the interference filter while improving image resolution. Through simulations, we show that the numerical aperture (NA) of the FOP drives inherent design tradeoffs: collection efficiency improves rapidly with a higher NA, but at the cost of resolution, increased device thickness, and fluorescence excitation efficiency. To illustrate this, we optimize two optical frontends with full-width at half maximums (FWHMs) of 8.3{\deg} and 45.7{\deg}. Implementing these designs, we show that angle-insensitivity requires filters on both sides of the FOP, due to scattering. In imaging experiments, the 520-$\mu$m-thick high-NA design is 59$\times$ more sensitive to fluorescence while only degrading resolution by 3.2$\times$. Alternatively, the low-NA design is capable of three-color fluorescence imaging with 110-$\mu$m resolution at a 1-mm working distance. Overall, we demonstrate a versatile optical frontend that is adaptable to a range of applications using different fluorophores, illumination configurations, and lensless imaging techniques.