Adaptive optical microscopy: the ongoing quest for a perfect image

Abstract

Adaptive optics is becoming a valuable tool for high resolution microscopy, providing correction for aberrations introduced by the refractive index structure of specimens. This is proving particularly promising for applications that require images from deep within biological tissue specimens. We review recent developments in adaptive microscopy, including methods and applications. A range of advances in different microscope modalities is covered and prospects for the future are discussed. INTRODUCTIONOptical microscopes have for a long time played a vital role in biomedical research. Their ability to provide multidimensional structural and functional information about a specimen in a non-invasive manner has permitted numerous scientific advances. These microscopes rely upon high-quality optical systems to operate at the optimum resolution, which is determined by the diffraction limit of light for conventional microscopes. However, even with perfect optical components, the performance of the microscope is affected by the optical properties of the specimen. Spatial variations in refractive index introduce aberrations as the light passes through the specimen-a problem that is exacerbated when imaging deeps into tissue. These aberrations detrimentally affect the resolution and contrast of microscope images, ultimately limiting the depth at which imaging is practical. Adaptive optics (AO) was introduced into microscopy in order to overcome this limitation. Dynamic correction elements, such as deformable mirrors (DMs) or spatial light modulators (SLMs) have been employed to compensate specimen-induced aberrations (Figure 1). New wavefront sensing and control schemes have been developed to adapt the correction elements.The first demonstrations of adaptive optical microscopy took place in the early 2000s. In the few years that followed, there were several innovative advances that set the scene for further research. The research in this period is well covered by two review articles 1,2 and a recent compiled volume, 3 so this will not be reproduced here. This present article provides a review of advances in aberration correction in adaptive microscopy that have taken place in the last half-decade. During this period, a wide range of AO techniques have emerged, which have considerably enhanced the available toolkit. Furthermore, the benefit of correction of specimen-induced aberrations has been shown in different areas, particularly (although not exclusively) in biomedical applications. We outline these technological

Subdiffraction optical manipulation of the charge state of nitrogen vacancy center in diamond

“…7,[12][13][14] Therefore, many optical super-resolution microscopy techniques have been developed to detect single NV centers. [13][14][15][16][17] Among these methods, stimulated emission depletion (STED) microscopy 12,[18][19][20] is one of the most promising. This method utilizes a doughnut-shaped laser to produce the position-dependent stimulated emission, which changes the fluorescence signal.…”

Computational optical coherence tomography [Invited]

“…Sophisticated optical designs can supress the static system aberrations [104,105], but they are not versatile for complex biological tissues that introduce unique, often dynamically changing, sample aberrations [106]. Hardware-based adaptive optics (HAO) has been introduced to correct the aberrations in incoherent imaging systems, such scanning laser ophthalmoscopy (SLO) [107] and fluorescence microscopy [108,109]. Integrated with OCT, HAO operates by using a wavefront sensor and wavefront corrector to dynamically measure and correct aberrations, has been developed for ophthalmology to study cellular details of the living human retina [110,111].…”

Parameterized Modeling of Spatially Varying PSF for Lens Aberration and Defocus

“…Therefore TLens, ZEnter, and ZExit may be the effective thickness and offsets of the thick-lens approximation and not the actual lens thickness or the locations of the physical lens pupils [16,20].…”