Quantum principles are increasingly being integrated into super-resolution microscopy for bio-imaging applications. This innovative approach leverages quantum sensing, which has already proven effective in enhancing the capabilities of microscopy. By utilizing quantum properties, these advanced techniques achieve unprecedented spatial resolution and sensitivity, thus opening new avenues in biological research and medical diagnostics. ## Optical Microscopy Optical microscopy has evolved significantly since the invention of the microscope over 500 years ago. The development of bioimaging can be traced back to the 17th century with a landmark publication, "Micrographia," by Robert Hooke. This work marked one of the first major uses of microscopes in biology, illustrating detailed drawings of the microscopic world. The capabilities and limitations of microscopes, particularly in terms of resolution, can be understood through both technical and fundamental perspectives. The fundamental limits are often described by the "diffraction limit," a concept developed by Ernst Abbe in 1873. This limit is intrinsic to the nature of light and the materials used to construct the microscope's optics. Vienna in 1873 was a pivotal point in the history of microscopy, as it was the birthplace of quantitative microscopy. Key figures in this development included: - Ernst Abbe, who not only introduced the diffraction limit but also established the scientific basis for the optics used in microscopes. - Karl Zeiss, a significant figure in the manufacturing of high-quality optical systems. - Otto Schott, a glassblower whose advancements in optical glass were crucial for improving microscope quality. Additionally, James Clerk Maxwell's work on electromagnetic theory, culminating in Maxwell's Equations, fundamentally supported the understanding of light as an electromagnetic wave, which underpins modern optical microscopy. --- ## Optical Resolution Optical resolution refers to the capability of an imaging system, such as a microscope, to distinguish fine details in the object being imaged. This ability is fundamentally limited by the diffraction barrier, often described by the Abbe Limit. This limit stipulates that the resolution is constrained to approximately half the wavelength of the light used for imaging. However, certain conditions under which the Abbe Limit applies also present opportunities to surpass this diffraction barrier. These include: - **Linear Optics**: Systems that obey the principles of linear optics are bound by this limit. - **Classical Fields**: The use of classical light fields, rather than quantum or coherent light, typically enforces the limit. - **Time-Independent Sample**: Samples that do not change during observation adhere strictly to the Abbe Limit. - **Homogeneous Sample**: Uniform samples without structural or compositional variations simplify the optical imaging but are more strictly limited by diffraction. - **No Extra Information**: The absence of additional data manipulations or advanced techniques like fluorescence or phase retrieval maintains the resolution limit. Recent advancements in super-resolution techniques challenge these conditions by manipulating one or more of these factors, thus enabling the visualization of details finer than what the classical diffraction limit would allow. ---- STED: Use light to quench Fluorescence. ![[Pasted image 20220106120058.png]] ![[Pasted image 20220106120402.png]] PALM/STORM use emitters that can be activated /deactivated by light. ![[Pasted image 20220106120513.png]] ## Where has quantum mechanics show benefits in the context of Optical Microscopy - Phase / Distance Measurement - Shot Noise Limit Measurement - [[Heisenberg Uncertainty Principle]] Limit N is the no. of Photons ![[Pasted image 20220106120818.png]] ![[Pasted image 20220106121121.png]] ![[Pasted image 20220106121603.png]] Quantum Emitters: One Photon at a Time! The photon stream from a quantum emitter is uniformly distributed. ![[Pasted image 20220106121747.png]] Medical imaging of deep tissue is usually associated with X-rays, MRI or other non-optical techniques, many of which are expensive.  Altough light can be transmitted through thick layers of tissue, **scattering of photons makes it impossible to recover an image**. However, through the combination of various technologies ranging from structured illumination to single photon detection and precise time for flight measurement, approaches based upon machine learning have opened up previously unexplored means of **reconstructing images from what superficially appears as random noise**. Using these approaches, we are working to **obtain images of objects buried in high scattering media and even through bone.** #toWrite