Millimetric Implantable Device for Extended in Vivo Fluorescence Recording

In vivo fluorescence sensing devices have recently gained considerable attention owing to their capabilities and potential in advancing biomedical research, clinical diagnostics, and therapeutic applications. In this work, we present a highly miniaturized, fully implantable device capable of excitation, detection, and recording of fluorescence signals, enabling continuous measurements of biological processes in vivo. The device was engineered to be minimally invasive, with a compact <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$5 \times 5 \times 5 \text{mm}^{3}$</tex> form factor. It incorporates an optical system integrating micro illumination and sensing units with a sub-mm2 footprint, achieving selective detection of fluorescence signals in close proximity. Additionally, the device features low-power on-board electronics and a customized bi-stable magnetic switch for remote activation, resulting in a device lifetime of over a month once the device is powered on. The device successfully recorded the infusion of green fluorescence protein (GFP) solution at a low concentration of 100 <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$\mu \mathrm{g}/\text{mL}$</tex> delivered at a rate of 4 <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$\mu \mathrm{L}/\mathrm{h}$</tex> for a 24-hour period, as well as the diffusion of a 150 <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$\mu \mathrm{L}$</tex> GFP bolus with a concentration of 200 <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$\mu \mathrm{g}/\text{mL}$</tex> over a 40-hour period, in a tissue-like phantom model made of gelatin. Further, the device was implanted into a living mouse for subcutaneous in vivo GFP recording as a proof of concept, and the fluorescence signal was successfully detected and recorded in the living animal.