Benjamin A. Flusberg

Fiber-optic fluorescence imaging

Optical fibers guide light between separate locations and enable new types of fluorescence imaging. Fiber-optic fluorescence imaging systems include portable handheld microscopes, flexible endoscopes well suited for imaging within hollow tissue cavities and microendoscopes that allow minimally invasive high-resolution imaging deep within tissue. A challenge in the creation of such devices is the design and integration of miniaturized optical and mechanical components. Until recently, fiber-based fluorescence imaging was mainly limited to epifluorescence and scanning confocal modalities. Two new classes of photonic crystal fiber facilitate ultrashort pulse delivery for fiber-optic two-photon fluorescence imaging. An upcoming generation of fluorescence imaging devices will be based on microfabricated device components.

High-speed, miniaturized fluorescence microscopy in freely moving mice

A central goal in biomedicine is to explain organismic behavior in terms of causal cellular processes. However, concurrent observation of mammalian behavior and underlying cellular dynamics has been a longstanding challenge. We describe a miniaturized (1.1 g mass) epifluorescence microscope for cellular-level brain imaging in freely moving mice, and its application to imaging microcirculation and neuronal Ca2+ dynamics.

In vivo brain imaging using a portable 3.9 gram two-photon fluorescence microendoscope

We introduce a compact two-photon fluorescence microendoscope based on a compound gradient refractive index endoscope probe, a DC micromotor for remote adjustment of the image plane, and a flexible photonic bandgap fiber for near distortion-free delivery of ultrashort excitation pulses. The imaging head has a mass of only 3.9 g and provides micrometer-scale resolution. We used portable two-photon microendoscopy to visualize hippocampal blood vessels in the brains of live mice.

Fast-scanning two-photon fluorescence imaging based on a microelectromechanical systems two- dimensional scanning mirror

Towards overcoming the size limitations of conventional two-photon fluorescence microscopy, we introduce two-photon imaging based on microelectromechanical systems (MEMS) scanners. Single crystalline silicon scanning mirrors that are 0.75 mm x 0.75 mm in size and driven in two dimensions by microfabricated vertical comb electrostatic actuators can provide optical deflection angles through a range of approximately16 degrees . Using such scanners we demonstrated two-photon microscopy and microendoscopy with fast-axis acquisition rates up to 3.52 kHz.

Fiber optic in vivo imaging in the mammalian nervous system

The compact size, mechanical flexibility, and growing functionality of optical fiber and fiber optic devices are enabling several new modalities for imaging the mammalian nervous system in vivo. Fluorescence microendoscopy is a minimally invasive fiber modality that provides cellular resolution in deep brain areas. Diffuse optical tomography is a non-invasive modality that uses assemblies of fiber optic emitters and detectors on the cranium for volumetric imaging of brain activation. Optical coherence tomography is a sensitive interferometric imaging technique that can be implemented in a variety of fiber based formats and that might allow intrinsic optical detection of brain activity at a high resolution. Miniaturized fiber optic microscopy permits cellular level imaging in the brains of behaving animals. Together, these modalities will enable new uses of imaging in the intact nervous system for both research and clinical applications.

A Portable Two-photon Fluorescence Microendoscope Based on a Two-dimensional Scanning Mirror

Towards overcoming the size limitations of conventional two-photon fluorescence microscopy for brain imaging in freely moving mice, we introduce a portable laser-scanning microendoscope based on a microelectromechanical systems (MEMS) two-dimensional (2-D) scanning mirror, compound gradient refractive index (GRIN) micro-lenses, and a photonic bandgap fiber (PBF). The microendoscope achieves fast line scanning acquisition rates up to 3.5 kHz and micron-scale imaging resolution.

Fast-scanning two-photon fluorescence imaging using a microelectromechanical systems (MEMS) two-dimensional scanning mirror

Towards overcoming the size limitations of conventional two-photon fluorescence microscopy, we introduce laser-scanning instrumentation based on a microelectromechanical systems (MEMS) scanner and describe two-photon microscopy and microendoscopy with fast-axis acquisition rates up to 3.5 kHz.

Fiber optic two-photon fluorescence microendoscopy: towards brain imaging in freely moving mice

We introduce a compact and lightweight (3.7 g) two-photon fluorescence microendoscope, which is based on a flexible photonic bandgap fiber and a DC micromotor, and which is designed for brain imaging in freely moving mice.