Molecular holography

分子全息术

• 批准号: RGPIN-2016-05018
• 负责人: Hewitt, Kevin
• 金额: $ 1.6万
• 依托单位: Dalhousie University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=615443
• 关键词: Molecular; holography

Imagine being able to simultaneously and uniquely track hundreds of molecules or proteins in a cell in three dimensions at millisecond rates. To achieve this goal I propose to combine a molecular-specific light scattering technique (Stimulated Raman spectroscopy - SRS) with the well-known three-dimensional imaging capability of holography, to create molecular holograms. In a Raman spectroscopy experiment, light is scattered at a unique set of wavelengths characteristic of the molecule or protein being illuminated. That is, the technique provides a fingerprint of the molecule in the scattered light - a spectral barcode. A further modification of this technique which uses two lasers (Stimulated Raman spectroscopy, SRS) creates a coherent scattered beam when the frequency difference between the lasers matches a molecular vibration. Holograms, like those commonly observed on our currency and credit cards, provide a three dimensional image of an object by combining coherently scattered laser light with the original light source. Molecular holography is the integration of these two techniques to create a map of the three-dimensional spatial distribution of a molecular vibration. My team is specifically interested in imaging the Epidermal Growth Factor Receptor, as it's overexpression is implicated in a number of cancers. However, the imaging technique would be widely applicable to any molecule or biomarker as long as an appropriate contrast agent is developed (e.g. appropriately functionalized gold or silver nanoparticles). This year, we completed successful proof-of-principle experiments that demonstrate conventional holograms of gold nanoparticles can be created and that coherent light emission (SRS) can be generated from molecules attached to the nanoparticles. Combining the two requires the integration of two lasers comprising a wavelength-tunable one and another with fixed wavelength, a pinhole, lock-in amplifier and a detector; along with the requisite software, developed at Dalhousie, to reconstruct the image. My team is now poised to create an imaging modality that has the potential to outperform fluorescence techniques. Molecular holography would offer several advantages, including capture of the 3D distribution of many more biomolecules with one exposure (holography), rather than reconstruction of a 3D profile from 2D images/slices. Unlike fluorescence imaging our technique has the very real potential to be label-free, thereby avoiding the perturbing effect of a foreign flurophore agent introduced to a cell. In the long term, label-free molecular holography could supplant fluorescence imaging as the cell biologists' modality of choice. My local, national and international network of collaborators will help ensure that the technique is adopted at leading institutions around the world.

想象一下，能够以毫秒级的速度在三维空间中同时独特地跟踪细胞中的数百个分子或蛋白质。为了实现这一目标，我建议将分子特异性光散射技术（受激拉曼光谱- SRS）与众所周知的全息三维成像能力相结合，以创建分子全息图。