Nano Diamond Biosensors to Monitor Intracellular Processes

By Benedette Cuffari, M.Sc.Mar 24 2017

Image Credit: Shutterstock.com/LjubomirArsic

Nanodiamonds (NDs) are diamond particles with their size in the micrometer (mm) scale. NDs are nontoxic, and have excellent mechanical and optical properties, high surface area and tunable surface structures¹.

Due to these special properties, NDs have found a wide variety of potential applications in the fields of drug delivery, bioimaging, tissue engineering, etc¹. NDs have naturally occurring defects called nitrogen-vacancy centers (NVs), which consists of a nitrogen (N) atom replacing the carbon (C) atom next to a vacancy in the diamond’s lattice structure.

These NV centers are sensitive to external magnetic fields, and act just like compasses². Due to this ability of NDs to measure the magnetic field non-invasively, NDs have been used as neural signal detecting diamond sensors². As a result of their near-complete carbon make-up, NDs with the NV defect exhibit excellent biocompatibility, long term stability and unique quantum sensing capabilities. NDs also demonstrated great promise in nanomedicine-based drug delivery, genes and proteins, fluorescent/photoacoustic imaging agents and in multifunctional intracellular signaling³. The fluorescence of the atomic-scale NVs present in the NDs depends on the electron spin states, enabling direct nanoscale sensing for magnetic field, electric field, temperature and mechanical force or pressure

Several physiological processes happen every second in every cell of the body. These cellular processes are accompanied by changes in concentrations of ions, reactive oxygen species, enzymes, nucleic acids, pH and redox potential³. Therefore, intracellular sensors capable of monitoring and/or measuring these variables would serve a great deal in elucidating various important cellular mechanisms, and could potentially lead to new possibilities in diagnostics and therapeutics at subcellular levels³. Due to the difficulties in developing selective detection principles, direct measurement of intracellular chemical reactions using ND-based biosensors has been challenging³.

Researchers at the Physikalisches Institute in Germany have recently developed programmable diamond quantum nanosensors to monitor the intracellular processes that play a key role in various biological and medical applications. Torsten Rendler’s team developed a hybrid nanosensor by using a polymer coating approach that involves the attachment of paramagnetic gadolinium (Gd³⁺) complexes to the NV centers of the NDs through surface engineering³. These nanosensors exhibited long-term stability and reduced non-specific binding, while also maintaining the convenience of chemical modification. The Gd³⁺ ion complexes were strictly programmed by connecting macrocyclic complexes of Gd³⁺ ions with a biocompatible copolymer shell on the NDs through selectively cleavable linkers,³ which allowed the Gd³⁺ ions to detach in response to changes in various physiological parameters³.

Torsten Rendler’s team also quantified the change in NV spin relaxation time by detecting the changes in the spin noise of the Gd³⁺ complexes, which showed that these sensors can be programmed efficiently to measure different parameters in physiological quantities³. This group of researchers also measured time-dependent changes in pH or redox potential at a mm scale in a microfluidic channel, which mimics the cellular environment. Interestingly, a single-step method to measure the spin relaxation rates was used to enable such pH and redox potential measurements. The results of the experimental data are found to be in accordance with results of the theoretical modelling of the NV spin interaction of Gd³⁺ complexes covering the NDs³.

The design and optimization of the ND-based biosensors can carry out signal transduction, recording and amplification simultaneously,  as well as measure the subtle changes in physiological variables, such as pH and redox potential³. This is possible through the measurement of the variance in Gd³⁺ complexes inside the polymer shell. The well-fitted first order release kinetics measurements in the conducted experiments demonstrated that these nanosensors respond precisely to a single predefined chemical parameter³. Furthermore, the polymer shell did not show swelling or deterioration, while also remaining insensitive to pH and ionic strength³.

This newly developed ND biosensor is based on the irreversible binding polymer, which is not efficient for extended periods of time, especially in conditions of higher cleavage rates. In a response to this limitation, the German research team is currently working on developing a reversibly-responding polymer coating on NDs that could potentially increase the duration of measurements of the ND biosensors³. The researchers believe that this ND biosensor has the potential to be applied in catalytic chemistry, cell biology and physiology. The development of molecular-sized NDs with NV centers can offer an improved spin sensitivity, which could therefore allow for a better sensitivity of the ND biosensors which are based on molecular sized NDs³.

References:

1. Mochalin, Vadym N., Olga Shenderova, Dean Ho, and Yury Gogotsi. "The Properties and Applications of Nanodiamonds." Nature Nanotechnology 7 (2012): 11-23. Web. http://www.nature.com/nnano/journal/v7/n1/pdf/nnano.2011.209.pdf#access
2. A. Cooper, E. Magesan, H. N. Yum, P. Cappellaro, Time-resolved magnetic sensing with electronic spins in diamond, Nature Communications, 2014. 
3. Rendler, Torsten, Jitka Neburkova, Ondrej Zemek, Jan Kotek, Andrea Zappe, Zhiqin Chu, Petr Cigler, and Jörg Wrachtrup. "Optical Imaging of Localized Chemical Events Using Programmable Diamond Quantum Nanosensors." Nature News. Nature Publishing Group, 20 Mar. 2017. Web. http://www.nature.com/articles/ncomms14701.
4. Shutterstock.com/LjubomirArsic

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