Fellows Call 2

High-precision optical Magnetometry using Nitrogen Vacancies in CVD diamond

Quantum sensing is poised to revolutionize the future of sensing platforms. We want to contribute to this revolution by developing a very compact and highly sensitive magnetometer operating at room temperature, based on Nitrogen-Vacancy (NV) center spins in diamond. The high sensitivity offers the potential to do nanoscale protein sensing and the compact size makes the sensor applicable for small mobile platforms. To achieve these goals, we will establish in-situ nitrogen doping of CVD diamond during the growth, so that the resulting NV centers have long coherence times. Moreover, we will engineer the diamond structure to increase the collection efficiency of the sensor. Finally, everything is going to be integrated in a small package which can be useful for applications including cold atom experiments magnetic field sensing, NMR, and neuron sensing.

Key words: Quantum Sensing, Diamond, Spin, Magnetic techniques

Exploration of Factors Influencing Clathrin-Mediated Endocytosis using Atomic Force Microscopy

Recently, High-speed atomic force microscopy (AFM) has seen a lot of progress and innovation, both in technology development and applications. In order to observe biomolecular interactions in liquid, we hope to combine the improved feedback control and reduced interaction forces of off-resonance tapping mode (ORT), with the required speed to time-resolve them that is achieved in conventional tapping mode. By using photothermal off-resonance tapping cantilever actuation, we can achieve similar or improved control of interaction forces between the cantilever and sample; and by using newly developed cantilevers, we can operate beyond the cantilever resonance frequency, which may allow us to approach or exceed the imaging speed capabilities of tapping mode AFM in similar applications.
In this project, I intend to use the new tools and protocols developed in our lab in order to track molecular interaction dynamics (currently of blunt-end DNA tripods and clathrin mediated endocytosis) in improved time resolution. Eventually, we hope to add the possibility of fluidic exchange as well as larger and more complex samples (such as cells) by adding a new scanner design, double-barrel cantilever and sample platform.
Learning more about these molecular interactions directly inside living cells will enable us to determine the cause of certain abnormalities in greater detail, as well as optimize drug and nanoparticle delivery systems for both research and medical purposes.

Key words: Clathrin-Mediated Endocytosis, Atomic Force Microscopy, Molecular assembly

Next generation microfluidic processor for Immunohistochemistry and in-situ hybridization

Immunohistochemistry & In-situ sequencing are the two most accurate and golden standard for biomarker-based cancer diagnostic techniques that rely on selective detection and localization of proteins or RNA sequences respectively, in cells of patient’s tumour tissue. Several factors limit the accuracy, reproducibility, and affordability of these analytical techniques. For example, different protocols with multiple steps for sample pre-preparation open the way for high variability in analysis in-between samples and between different laboratories/pathologists and can compromise specimen antigenicity. Additionally, the long-time of pre-processing and analysis of samples adds substantial cost to the diagnostic process. On the micro and nano level, different factors limit the performance of such techniques. For example, diffusion-limited reactions lead to a longer staining time, non-specific binding leads to a high background signal, possible steric repulsion in-between antibodies themselves and between target antigens lead to poor staining, and the need for higher volumes of expensive antibody reagents to ensure reproducible and sufficient staining.

We develop microfluidic systems for automating and improving such analysis methods while reducing time, cost, and infrastructure needed. Moreover, we integrate AC electro-kinetic technologies with microfluidics to manipulate fluids to decrease protocol time while reducing cost of analysis and improving the signal to background ratio.

Key words: Microfluidics, Diagnostics, In-situ sequencing, Cancer