Optical single-molecule sensors are gaining ground in several medical applications due to their promise of sensitivity and accuracy [1], [2]. Many optical sensors have been developed relying on fluorescence-based labeling or plasmonic transducers [3]. Especially label-free sensing techniques based on surface plasmon resonance (SPR) have been studied extensively, including localized surface plasmon resonance (LSPR) [4]. Methods based on (L)SPR measure the binding of an analyte as a change in the (local) refractive index, which results in a shift of the corresponding extinction or scattering wavelength. These methods are mainly popular due to the ease of integration in chip-based devices and their promise in point-of-care sensing applications [4].
By introducing LSPR, numerous applications have since been made possible, including the preparation of ordered nanoparticle structures, biosensing, separation, and gene and drug delivery. However, their application to the real world is limited due to the long and tedious process needed to functionalize these AuNPs. This stems from the fact that both DNA and gold particles are negatively charged, therefore efficient interaction is possible only at high salt concentrations. In this assignment, you will work on a method to tune DNA density on large AuNPs (>20 nm diameter), while being much faster than traditional methods, as presented in figure 1 [5].
Figure 1. Top part: conventional salt-aging method to functionalize gold nanoparticles with thiolated DNA, which can take up to 3 days. Down part: new “synergetic” method that takes less than two hours [5].
Research questions
- This assignment aims to address the following research questions:
- What is the optimal density of DNA on the AuNP?
- Is this optimal density sequence dependent?
- Can these AuNPs be used for biosensing approaches in solution / on a surface?
- Can antibodies/aptamers also be functionalized on the AuNPs using the same method?
Contact person:
References
[1] N. Akkilic, S. Geschwindner, and F. Höök, “Single-molecule biosensors: Recent advances and applications,” Biosensors and Bioelectronics, vol. 151. 2020, doi: 10.1016/j.bios.2019.111944.
[2] G. Luka et al., “Microfluidics integrated biosensors: A leading technology towards lab-on-A-chip and sensing applications,” Sensors (Switzerland), vol. 15, no. 12. MDPI AG, pp. 30011–30031, Dec. 01, 2015, doi: 10.3390/s151229783.
[3] C. Chen and J. Wang, “Optical biosensors: an exhaustive and comprehensive review,” Analyst, vol. 145, no. 5, pp. 1605–1628, Mar. 2020, doi: 10.1039/C9AN01998G.
[4] A. B. Taylor and P. Zijlstra, “Single-Molecule Plasmon Sensing: Current Status and Future Prospects,” ACS Sensors, vol. 2, no. 8. pp. 1103–1122, 2017, doi: 10.1021/acssensors.7b00382.
[5] Li, J., Zhu, B., Yao, X., Zhang, Y., Zhu, Z., Tu, S., ... & Yang, C. J. (2014). Synergetic approach for simple and rapid conjugation of gold nanoparticles with oligonucleotides. ACS applied materials & interfaces, 6(19), 16800-16807.