A bipolar (BP) nanosecond electric pulse (nsEP) exposure generates reduced calcium influx compared to a unipolar (UP) nsEP. This attenuated physiological response from a BP nsEP exposure is termed “bipolar cancellation” (BPC). The predominant BP nsEP parameters that induce BPC consist of a positive polarity (↑) front pulse followed by the delivery of a negative polarity (↓) back pulse of equal voltage and width; thereby the duration is twice a UP nsEP exposure. We tested these BPC parameters, and discovered that a BP nsEP with symmetrical pulse widths is not required to generate BPC. For example, our data revealed the physiological response initiated by a ↑900 nsEP exposure can be cancelled by a second pulse that is a third of its duration.  However, we observed a complete loss of BPC from a ↑300 nsEP followed by a ↓900 nsEP exposure. Spatiotemporal analysis revealed these asymmetrical BP nsEP exposures generate distinct local YO-PRO®-1 uptake patterns across the plasma membrane. From these findings, we generated a conceptual model that suggests BPC is a phenomenon balanced by localized charging and discharging events across the membrane.

Spontaneous Raman scattering is a powerful tool for chemical sensing and imaging but suffers from a weak signal. In this Letter, we present an application of adaptive optics to enhance the Raman scattering signal detected through a turbid, optically thick material. This technique utilizes recent advances in wavefront shaping techniques for focusing light through a turbid media and applies them to chemical detection to achieve a signal enhancement with little sacrifice to the overall simplicity of the experimental setup. With this technique, we demonstrate an enhancement in the Raman signal from titanium dioxide particles through a highly scattering material. This technique may pave the way to label-free tracking using the optical memory effect.

The ability to characterize the combined structural, functional, and thermal properties of biophysically dynamic samples is needed to address critical questions related to tissue structure, physiological dynamics, and disease progression. Towards this, we have developed an imaging platform that enables multiple nonlinear imaging modalities to be combined with thermal imaging on a common sample. Here we demonstrate label-free multimodal imaging of live cells, excised tissues, and live rodent brain models. While potential applications of this technology are wide-ranging, we expect it to be especially useful in addressing biomedical research questions aimed at the biomolecular and biophysical properties of tissue and their physiology.

Significance: Infrared neural stimulation (INS) utilizes pulsed infrared light to selectively elicit neural activity without exogenous compounds. Despite its versatility in a broad range of biomedical applications, no comprehensive comparison of factors pertaining to the efficacy and safety of INS such as wavelength, radiant exposure, and optical spot size exists in the literature.

Optical second harmonic generation is a fundamental nonlinear effect with a large impact on laser technology and optical imaging/sensing. For most practical applications of second harmonic generation, high conversion efficiency is required. However, many techniques used to achieve high efficiency are limited to fabrication methods and optical energy requirements. Here, we investigate and demonstrate substantial enhancement in the conversion efficiency of second harmonic generation in a nonlinear crystal via the application of wavefront shaping. In a one-dimensional understanding of second harmonic generation, a phase offset applied to the fundamental wave has no effect on the intensity of the generated light. We show that when the pump field is not a plane wave, enhanced conversion efficiency can be controlled by the application of a phase mask to the fundamental beam. This investigation of the dependence of conversion efficiency upon the transverse phase profile of the incident pump laser yields the promise of new ways to enhance nonlinear generation with limited optical energy and without the need for specific fabrication techniques.

14The ability to characterize the combined structural, functional, and thermal properties of 15 biophysically dynamic samples is needed to address critical questions related to tissue structure, 16physiological dynamics, and disease progression. Towards this, we have developed an imaging 17 platform that enables multiple nonlinear imaging modalities to be combined with thermal 18imaging on a common sample. Here we demonstrate label-free multimodal imaging of live cells, 19excised tissues, and live rodent brain models. While potential applications of this technology are 20 wide-ranging, we expect it to be especially useful in addressing biomedical research questions 21 aimed at the biomolecular and biophysical properties of tissue and their physiology. 22

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