EU SuperCol

Rational design of super-selective and responsive colloidal particles for biosensing

Colloidal-particle-based materials combine a large surface-to-volume ratio with excellent control over building block size, shape and biochemical functionalization. The interactions of colloidal particles with their local environment are dominated by the chemical organization on their interface. This provides unique opportunities to develop particle-based sensors to detect e.g. biomolecules in immunoassays, or to detect membrane receptors and subsequently release cargo for drug delivery. Our cells use such sensing mechanisms continuously and show a remarkable ability to exploit molecular events to balance and steer complex macroprocesses – far beyond what we ever imagined.

To date, we have had only limited success in capturing this unique level of control in artificial particle-based sensing systems. Or in other words: in order to realize particle-based sensors with the sensitivity, selectivity and kinetic control of their biological equivalents, we need to create surfaces with a quantified and rationally designed number, distribution, and affinity of bio-active molecules.

In this joint European project, we are going to address two functionalities that remain challenging to achieve. Responsiveness (i.e. the ability to adapt the number, distribution and affinity of bio-active molecules on the particle’s interface in response to external cues) and super-selectivity (i.e. exploiting multivalent interactions to obtain a highly non-linear dependence of binding strength on the receptor density). These functionalities depend on tight and quantitative control over the number, distribution and activity of interface chemical groups, which is hampered by the lack of methods to visualize these groups with chemical specificity and at the single-molecule level. This prohibits rational optimization of functionalization protocols needed to achieve design control over particle functionality.

The advent of super-resolution microscopy and novel cryo-TEM approaches provides us with a timely and unique opportunity to quantify and control the sensory response of particle-surfaces at the single-molecule level. Specifically, the emerging ability to quantify the particle’s chemical interface using super-resolution microscopy will open the window to rationally design sensitive, responsive, and selective sensors with quantitative functionality.