Mid-infrared microscopy via position correlations of undetected photons.

Quantum imaging with undetected photons (QIUP) has recently emerged as a new powerful imaging tool. Exploiting the spatial entanglement of photon pairs, it allows decoupling of the sensing and detection wavelengths, facilitating imaging in otherwise challenging spectral regions by leveraging mature silicon-based detection technology. All existing implementations of QIUP have so far utilised the momentum correlations within the biphoton states produced by spontaneous parametric downconversion. Here, for the first time, we implement and examine theoretically and numerically the complementary scenario - utilising the tight position correlations formed within photon pairs at birth. This image plane arrangement facilitates high resolution imaging with comparative experimental ease, and we experimentally show resolutions below 10 µm at a sensing wavelength of 3.7 µm. Moreover, we present a quantitative numerical model predicting the imaging capabilities of QIUP for a wide range of parameters. Finally, by imaging mouse heart tissue at the mid-IR to reveal morphological features on the cellular level, we further demonstrate the viability of this technique for the life sciences. These results offer new perspectives on the capabilities of QIUP for label-free widefield mid-IR microscopy, enabling real-world biomedical as well as industrial imaging applications.

Microscopy with undetected photons in the mid-infrared.

Owing to its capacity for unique (bio)-chemical specificity, microscopy with mid-infrared (IR) illumination holds tremendous promise for a wide range of biomedical and industrial applications. The primary limitation, however, remains detection, with current mid-IR detection technology often marrying inferior technical capabilities with prohibitive costs. Here, we experimentally show how nonlinear interferometry with entangled light can provide a powerful tool for mid-IR microscopy while only requiring near-IR detection with a silicon-based camera. In this proof-of-principle implementation, we demonstrate widefield imaging over a broad wavelength range covering 3.4 to 4.3 µm and demonstrate a spatial resolution of 35 µm for images containing 650 resolved elements. Moreover, we demonstrate that our technique is suitable for acquiring microscopic images of biological tissue samples in the mid-IR. These results form a fresh perspective for potential relevance of quantum imaging techniques in the life sciences.

Measuring sickle cell morphology during blood flow.

During a sickle cell crisis in sickle cell anemia patients, deoxygenated red blood cells may change their mechanical properties and block small blood vessels, causing pain, local tissue damage, and possibly organ failure. Measuring the structural and morphological changes in sickle cells is important for understanding the factors contributing to vessel blockage and for developing an effective treatment. In this work, we image blood cells from sickle cell anemia patients using spectrally encoded flow cytometry, and analyze the interference patterns between reflections from the cell membranes. Using a numerical simulation for calculating the interference pattern obtained from a model of a red blood cell, we propose an analytical expression for the three-dimensional shape of characteristic sickle cells and compare our results to a previously suggested model. Our imaging approach offers new means for analyzing the morphology of sickle cells, and could be useful for studying their unique physiological and biomechanical properties.

Experimental Proof for the Role of Nonlinear Photoionization in Plasmonic Phototherapy.

Targeting individual cells within a heterogeneous tissue is a key challenge in cancer therapy, encouraging new approaches for cancer treatment that complement the shortcomings of conventional therapies. The highly localized interactions triggered by focused laser beams promise great potential for targeting single cells or small cell clusters; however, most laser-tissue interactions often involve macroscopic processes that may harm healthy nearby tissue and reduce specificity. Specific targeting of living cells using femtosecond pulses and nanoparticles has been demonstrated promising for various potential therapeutic applications including drug delivery via optoporation, drug release, and selective cell death. Here, using an intense resonant femtosecond pulse and cell-specific gold nanorods, we show that at certain irradiation parameters cell death is triggered by nonlinear plasmonic photoionization and not by thermally driven processes. The experimental results are supported by a physical model for the pulse-particle-medium interactions. A good correlation is found between the calculated total number and energy of the generated free electrons and the observed cell death, suggesting that femtosecond photoionization plays the dominant role in cell death.