Opportunities for multimodal quantum sensing in intracellular environments

Nanoscale quantum sensors offer an opportunity to probe systems with high sensitivity and spatial resolution. Nitrogen vacancy centers (NV) in diamond have emerged as one of the leading candidates for room temperature quantum sensing due to their stable photoluminescence and exceptional electronic spin coherence at room temperature. The ground-state spin transition that is utilised for sensing can be effectively uncoupled from fluctuations in background fluorescence which means that NV measurements remain unaffected by local changes in the optical environment. Combined with their minimal cytotoxicity even at high concentrations, amenability to surface functionalization, and robustness against changes in pH, this makes NVs a promising candidate for sensing in biological systems. This optical addressable spin-based quantum sensor can address a wide selection of sensing modalities, from temperature, magnetic field and electric field which can be sensed directly by the NV to pH which can be targeted with the aid of surface functionalisation. While these modalities have so far been demonstrated individually, the ability to simultaneously sense multiple modalities would provide a powerful tool capable of investigating perturbation and response. This is particularly useful in biological samples where there is significant local inhomogeneity within cells and variability among cells making it difficult to correlate independent measurements. There is known to be significant interdependence between physical properties in biological systems, for example, temperature can often affect viscosity, the speed of chemical reactions and the rate of cell division. Understanding the relationship between two properties is difficult to capture effectively if the level of an external perturbation and the level of response cannot be measured simultaneously. In this thesis, the challenges in combining quantum sensing measurements with biological systems are addressed. A Quantum Biosensing Chip (QuBiC) was developed which facilitates the repeatable and controllable delivery of microwaves to the sample with minimal setup time. This allowed the effects of heating caused by the microwave excitation required for quantum sensing to be quantified in biological cells and a threshold established for microwave power that should be used. This quantum sensing chip, combined with a double- plane orbital tracking mechanism was used to perform thermometry and nanorheology measurements simultaneously. Temperature measurements were performed using optically detected magnetic resonance (ODMR) and combined with the subdiffraction resolution single- particle tracking a sensitivity of 2.3 K/√Hz and 3.7 nm spatial resolution was achieved. This dual-modal sensor is used to study the temperature dependence of viscosity and viscoelasticity in abiotic fluidic environments. The sensor is then employed inside live human cancer cells to reveal different regimes of intracellular dynamics including evidence of active trafficking and the subcellular response to external temperature changes. The research in this thesis pushes forward the field of quantum biosensing by introducing a quantum sensing chip which overcomes the challenges of combining quantum sensing with biological samples. The simultaneous temperature and rheological measurements offer an opportunity to study the temperature dependence of rheological properties on the nanoscale which is a topic of particular interest in biological samples.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2023

Author dc:creator

• Shanahan, Louise

Advisor dc:contributor.advisor

• Atatüre, Mete

• Nanodiamonds
• Nitrogen Vacancy Center
• Quantum Sensing
• Temperature

Licence

• https://www.repository.cam.ac.uk/bitstreams/cdbda9fd-fd71-4051-b910-3aa9d2da88f7/download
• http://purl.org/NET/rdflicense/allrightsreserved

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.120324

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/387600