Manipulating and focusing light deep inside biological tissue and tissue-like complex media has been desired for long yet considered challenging. One feasible strategy is through optical wavefront engineering, where the optical scattering-induced phase distortions are time reversed or pre-compensated so that photons travel along different optical paths interfere constructively at the targeted position within a scattering medium. To define the targeted position, an internal guidestar is needed to guide or provide a feedback for wavefront engineering. It could be injected or embedded probes such as fluorescence or nonlinear microspheres, ultrasonic modulation, as well as absorption perturbation. Here we propose to use a magnetically controlled optical absorbing microsphere as the internal guidestar. Using a digital optical phase conjugation system, we obtained sharp optical focusing within scattering media through time-reversing the scattered light perturbed by the magnetic microsphere. Since the object is magnetically controlled, dynamic optical focusing is allowed with a relatively large field-of-view by scanning the magnetic field externally. Moreover, the magnetic microsphere can be packaged with an organic membrane, using biological or chemical means to serve as a carrier. Therefore, the technique may find particular applications for enhanced targeted drug delivery, and imaging and photoablation of angiogenic vessels in tumours.

Focused and controllable optical delivery beyond the optical diffusion limit in biological tissue has been desired for long yet considered challenging. Digital optical phase conjugation (DOPC) has been proven promising to tackle this challenge. Its broad applications, however, have been hindered by the system’s complexity and rigorous requirements, such as the optical beam quality, the pixel match between the wavefront sensor and wavefront modulator, as well as the flatness of the modulator’s active region. In this paper, we present a plain yet reliable DOPC setup with an embedded four-phase, non-iterative approach that can rapidly compensate for the wavefront modulator’s surface curvature, together with a non-phase-shifting in-line holography method for optical phase conjugation in the absence of an electro-optic modulator (EOM). In experiment, with the proposed setup the peak-to-background ratio (PBR) of optical focusing through a standard ground glass in experiment can be improved from 460 up to 23,000, while the full width at half maximum (FWHM) of the focal spot can be reduced from 50 down to 10 μm. The focusing efficiency, as measured by the value of PBR, reaches nearly 56.5% of the theoretical value. Such a plain yet efficient implementation, if further engineered, may potentially boost DOPC suitable for broader applications.

While propagating inside the strongly scattering biological tissue, photons lose their incident directions beyond one transport mean free path (TMFP, [Formula: see text]1 millimeter (mm)), which makes it challenging to achieve optical focusing or clear imaging deep inside tissue. By manipulating many degrees of the incident optical wavefront, the latest optical wavefront engineering (WFE) technology compensates the wavefront distortions caused by the scattering media and thus is toward breaking this physical limit, bringing bright perspective to many applications deep inside tissue, e.g., high resolution functional/molecular imaging, optical excitation (optogenetics) and optical tweezers. However, inside the dynamic turbid media such as the biological tissue, the wavefront distortion is a fast and continuously changing process whose decorrelation rate is on timescales from milliseconds (ms) to microseconds ([Formula: see text]s), or even faster. This requires that the WFE technology should be capable of beating this rapid process. In this review, we discuss the major challenges faced by the WFE technology due to the fast decorrelation of dynamic turbid media such as living tissue when achieving light focusing/imaging and summarize the research progress achieved to date to overcome these challenges.