Multiphoton microscopy (MPM) has found a niche in the world of biological imaging as the best noninvasive means of fluorescence microscopy in tissue explants and living animals. Coupled with transgenic mouse models of disease and 'smart' genetically encoded fluorescent indicators, its use is now increasing exponentially. Properly applied, it is capable of measuring calcium transients 500 microm deep in a mouse brain, or quantifying blood flow by imaging shadows of blood cells as they race through capillaries. With the multitude of possibilities afforded by variations of nonlinear optics and localized photochemistry, it is possible to image collagen fibrils directly within tissue through nonlinear scattering, or release caged compounds in sub-femtoliter volumes.

/pdf/nonlinear-magic-multiphoton-microscopy-in-the-biosciences-3fszv5aq8z.pdf

Nonlinear magic: multiphoton microscopy in the biosciences

Quantum control is concerned with active manipulation of physical and chemical processes on the atomic and molecular scale. This work presents a perspective of progress in the field of control over quantum phenomena, tracing the evolution of theoretical concepts and experimental methods from early developments to the most recent advances. Among numerous theoretical insights and technological improvements that produced the present state-of- the-art in quantum control, there have been several breakthroughs of foremost importance. On the technology side, the current experimental successes would be impossible without the development of intense femtosecond laser sources and pulse shapers. On the theory side, the two most critical insights were (i) realizing that ultrafast atomic and molecular dynamics can be controlled via manipulation of quantum interferences and (ii) understanding that optimally shaped ultrafast laser pulses are the most effective means for producing the desired quantum interference patterns in the controlled system. Finally, these theoretical and experimental advances were brought together by the crucial concept of adaptive feedback control (AFC), which is a laboratory procedure employing measurement-driven, closed-loop optimization to identify the best shapes of femtosecond laser control pulses for steering quantum dynamics towards the desired objective. Optimization in AFC experiments is guided by a learning algorithm, with stochastic methods proving to be especially effective. AFC of quantum phenomena has found numerous applications in many areas of the physical and chemical sciences, and this paper reviews the extensive experiments. Other subjects discussed include quantum optimal control theory, quantum control landscapes, the role of theoretical control

https://iopscience.iop.org/article/10.1088/1367-2630/12/7/075008/pdf

Control of quantum phenomena: past, present and future

It is control that turns scientific knowledge into useful technology: in physics and engineering it provides a systematic way for driving a dynamical system from a given initial state into a desired target state with minimized expenditure of energy and resources As one of the cornerstones for enabling quantum technologies, optimal quantum control keeps evolving and expanding into areas as diverse as quantum-enhanced sensing, manipulation of single spins, photons, or atoms, optical spectroscopy, photochemistry, magnetic resonance (spectroscopy as well as medical imaging), quantum information processing and quantum simulation In this communication, state-of-the-art quantum control techniques are reviewed and put into perspective by a consortium of experts in optimal control theory and applications to spectroscopy, imaging, as well as quantum dynamics of closed and open systems We address key challenges and sketch a roadmap for future developments

/pdf/training-schrodinger-s-cat-quantum-optimal-control-ra2pns71lh.pdf

Training Schrödinger’s cat: quantum optimal control

The ability to dynamically image features deep within living organisms, permitting real-time analysis of cellular structure and function, is important for biological science. This Review article discusses multiphoton microscopy capable of such analysis, along with technologies that are pushing the limits of phenomena that can be quantitatively imaged.

/pdf/advances-in-multiphoton-microscopy-technology-42gqk18ef1.pdf

Advances in multiphoton microscopy technology

We introduce a noninterferometric single beam method to characterize and compensate the spectral phase of ultrashort femtosecond pulses accurately. The method uses a pulse shaper that scans calibrated phase functions to determine the unknown spectral phase of a pulse. The pulse shaper can then be used to synthesize arbitrary phase femtosecond pulses or it can introduce a compensating spectral phase to obtain transform-limited pulses. This method is ideally suited for the generation of tailored spectral phase functions required for coherent control experiments.

/pdf/multiphoton-intrapulse-interference-iv-ultrashort-laser-1cktr1sn5o.pdf

Multiphoton intrapulse interference. IV. Ultrashort laser pulse spectral phase characterization and compensation.

Nonlinear optical processes are controlled by modulating the phase of ultrafast laser pulses taking advantage of multiphoton intrapulse interference. Experimental results show orders of magnitude control over two- and three-photon excitation of large organic molecules in solution using specific phase functions. We show simulations on the effect of phase modulation on the second- and third-order amplitude of the electric field spectrum, and demonstrate that the observed control is not caused by simple changes in peak intensity.

Multiphoton intrapulse interference. II. Control of two- and three-photon laser induced fluorescence with shaped pulses

We explore and demonstrate the use of phase-modulated ultrafast laser pulses for controlling nonlinear optical processes in large molecules, proteins, and solid materials. Our experiments illustrate that in condensed phases, when spectra are broad, the spectrum of the nth-order electric field, determined by multiphoton intrapulse interference, plays a major role in controlling multiphoton excitation. These findings determine key parameters (amplitude, period, and symmetry of the phase function) for coherent femtosecond laser control in condensed phases.

Multiphoton Intrapulse Interference. 1. Control of Multiphoton Processes in Condensed Phases

Selective two-photon excitation of fluorescent probe molecules using phase-only modulated ultrashort 15-fs laser pulses is demonstrated. The spectral phase required to achieve the maximum contrast in the excitation of different probe molecules or identical probe molecules in different micro-chemical environments is designed according to the principles of multiphoton intrapulse interference (MII). The MII method modulates the probabilities with which specific spectral components in the excitation pulse contribute to the two-photon absorption process due to the dependence of the absorption on the power spectrum of E2(t) [1–3]. Images obtained from a number of samples using the multiphoton microscope are presented.

/pdf/selective-two-photon-microscopy-with-shaped-femtosecond-1mc98yu1d8.pdf

Selective two-photon microscopy with shaped femtosecond pulses.

Phase modulation, through its influence on the probability of two-photon excitation at specific frequencies, is used to probe a molecule's microscopic chemical environment. The spectral phase required is designed according to the principles of multiphoton intrapulse interference. We show experimental results where phase modulation of 20 fs pulses from a titanium sapphire laser oscillator controls the intensity of two-photon induced fluorescence from the pH-sensitive dye 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) in solution. We show that the dependence of fluorescence yield on the phase can be utilized as a means of distinguishing molecules in different environments. Consequently, this method can be used to achieve selective multiphoton microscopy. To illustrate this capability, we show images where phase modulation was used to selectively excite HPTS in acidic or basic microscopic regions.

/pdf/multiphoton-intrapulse-interference-3-probing-microscopic-41jqujomlg.pdf

Multiphoton Intrapulse Interference 3: Probing Microscopic Chemical Environments

The response of atoms and molecules to intense 1013 — 1015 W/cm2 lasers was investigated using two-dimensional (time-frequency) four-wave mixing. The data reveal a transition from a molecular response to a purely electronic (plasma) response.

Katherine A. Walowicz

Papers

Multiphoton intrapulse interference. II. Control of two- and three-photon laser induced fluorescence with shaped pulses

Multiphoton Intrapulse Interference. 1. Control of Multiphoton Processes in Condensed Phases

Selective two-photon microscopy with shaped femtosecond pulses.

Multiphoton Intrapulse Interference 3: Probing Microscopic Chemical Environments

Two-dimensional (time-frequency) femtosecond four-wave mixing at 10 14 W/cm 2 : molecular and electronic response