Using short-wave infrared wavelength advantages, we demonstrate one-photon fluorescence confocal microscopy of adult mouse brains with penetration depths up to 1.7mm. This is achieved by labeling quantum dots with 1300 nm excitation and 1700 nm emission and detecting them with a single-photon superconducting nanowire detector.

Optical microscopy is a valuable tool for in vivo monitoring of biological structures and functions because of its noninvasiveness. However, imaging deep into biological tissues is challenging due to the scattering and absorption of light. Previous research has shown that the two optimal wavelength windows for high-resolution deep mouse brain imaging are around 1300 and 1700 nm. However, one-photon fluorescence imaging in the wavelength region has been highly challenging due to the poor detection efficiency of currently available detectors. To fully utilize this wavelength advantage, we demonstrated here one-photon confocal fluorescence imaging of deep mouse brains with an excitation wavelength of 1310 nm and an emission wavelength within the 1700 nm window. Fluorescence emission at 1700 nm was detected by a custom-built superconducting nanowire single-photon detector (SNSPD) optimized for detection between 1600 nm and 2000 nm with low detection noise and high detection efficiency. With the PEGylated quantum dots and SNSPD both positioned at the optimal imaging window for deep tissue penetration, we demonstrated in vivo one-photon confocal fluorescence imaging at approximately 1.7 mm below the surface of the mouse brain, through the entire cortical column and into the hippocampus region with a low-cost continuous-wave laser source and low excitation power. We further discussed the significance of the staining inhomogeneity in determining the depth limit of one-photon confocal fluorescence imaging. Our work may motivate the further development of long wavelength fluorescent probes, and inspire innovations in high-efficiency, high-gain, and low-noise long wavelength detectors for biological imaging.

In the past decade, superconducting nanowire single-photon detectors (SNSPDs) have gradually become an indispensable part of any demanding quantum optics experiment. Until now, most SNSPDs have been coupled to single-mode fibers. SNSPDs coupled to multimode fibers have shown promising efficiencies but have yet to achieve high time resolution. For a number of applications ranging from quantum nano-photonics to bio-optics, high efficiency and high time resolution are desired at the same time. In this paper, we demonstrate the role of polarization on the efficiency of multimode-fiber-coupled detectors and fabricated high-performance 20 µm, 25 µm, and 50 µm diameter detectors targeted for visible, near-infrared, and telecom wavelengths. A custom-built setup was used to simulate realistic experiments with randomized modes in the fiber. We achieved over 80% system efficiency and <20 ps timing jitter for 20 µm SNSPDs. Also, we realized 70% system efficiency and <20 ps timing jitter for 50 µm SNSPDs. The high-efficiency multimode-fiber-coupled SNSPDs with unparalleled time resolution will benefit various quantum optics experiments and applications in the future.