Microscopy with undetected photons in the mid-infrared

Owing to its capacity for unique (bio)-chemical specificity, microscopy withmid-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. This has lead to approaches that shift detection towavelengths into the visible regime, where vastly superior silicon-based cameratechnology is available. Here, we experimentally show how nonlinear interferometry with entangled light can provide a powerful tool for mid-IR microscopy, while only requiring near-infrared detection with a standard CMOS camera. In this proof-of-principle implementation, we demonstrate intensity imaging overa broad wavelength range covering 3.4-4.3um and demonstrate a spatial resolution of 35um for images containing 650 resolved elements. Moreover, we demonstrate our technique is fit for purpose, acquiring microscopic images of biological tissue samples in the mid-IR. These results open a new perspective for potential relevance of quantum imaging techniques in the life sciences.Comment: back-to-back submission with arXiv:2002.05956, Anna V. Paterova, Sivakumar M. Maniam, Hongzhi Yang, Gianluca Grenci, and Leonid A. Krivitsky, "Hyperspectral Infrared Microscopy With Visible Light

Microscopy with undetected photons in the mid-infrared

Die einzigartige (bio)-chemische Spezifität der mittleren Infrarotmikroskopie birgt ein enormes Potential für eine breite Palette biomedizinischer und industrieller Anwendungen. Eine wesentliche Einschränkung ergibt sich jedoch durch die unzureichenden Detektionsmöglichkeiten in diesem Wellenlängenbereich, da derzeitige Mittelinfrarot-Detektoren meist durch geringere Leistungsfähigkeit bei deutlich höheren Anschaffungskosten gekennzeichnet sind. Dementsprechend verlagern neuentwickelte Technologien mitunter die Detektion in den sichtbaren Spektralbereich, in dem eine weitaus bessere, Silizium-basierte Kameratechnologie verfügbar ist. Ein solches Verfahren, das im Mittelpunkt dieser Arbeit steht, ist die Quantenbildgebung mit undetektiereten Photonen, welche sich zunehmend als leistungsfähiges Werkzeug für Infrarot-Bildgebung entwickelt. Der optische Aufbau basiert auf nichtlinearer Interferometrie bei der räumlich verschränkte, nicht-entartete Photonenpaare die Entkopplung der Analyse- und Detektionswellenlängen ermöglicht. Entsprechend wird die Bildgebung im mittleren Infrarotbereich durch die Detektion von Nahinfrarotlicht mit einer handelsüblichen CMOS-Kamera realisiert. In dieser Arbeit wird die beschriebene Methode auf die Mikroskopie übertragen, wodurch Abbildungen biologischer Gewebeproben im mittleren Infrarotbereich mit einer Auflösung von geringer als 10 Mikrometer angefertigt werden können. Darüber hinaus werden zwei Abbildungsregime untersucht, die auf den komplementären Impuls- und Positionskorrelationen der Photonenpaare basieren. Weiterführende Möglichkeiten der Kombination von Quanten-Bildgebung mit unentdeckten Photonen und FTIR-Spektroskopie zum Zwecke der räumlich-spektral kontinuierlichen Datenerfassung werden besprochen. Die vorgestellten Ergebnisse stellen die Entwicklungsfähigkeit der Quantenbildgebung mit unentdeckten Photonen unter Beweis und demonstrieren ihr Potential für praxisnahe Anwendungen in der Biomedizin und der Industrie.The unique (bio)-chemical specificity of mid-infrared (IR) microscopy holds tremendous promise for a wide range of biomedical and industrial applications. Significant limitation, however, arises from poor detection capabilities in this wavelengths range, with current mid-IR detection technology often marrying inferior technical capabilities with prohibitive costs. Accordingly, emerging approaches shift detection into the visible regime, where vastly superior silicon-based camera technology is available. One such technique, and the one that is in the center of this thesis is quantum imaging with undetected photons (QIUP), which has recently emerged as a new powerful imaging tool. The optical layout is based on nonlinear interferometry, where spatially entangled non-degenerate photon pairs enable the decoupling of the sensing and detection wavelengths, facilitating mid-IR wide-field imaging through the detection of near-IR light with an off-the-shelf CMOS camera. Additionally, the method is expanded towards microscopy, attaining sub-10 μm resolution, demonstrating our technique is fit for purpose, acquiring microscopic images of biological tissue samples in the mid-IR. Additionally, two imaging regimes are explored, based on the complementary momentum and position correlations. A comparison between the two regimes is presented and some limitations of the technique are discussed. Further efforts of combining QIUP with Fourier Transform IR spectroscopy for spatio-spectral continuous data acquisition are reviewed. The presented results demonstrate the achieved progress towards advancing QIUP to enable real-world biomedical as well as industrial imaging applications

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