Platform Development

Ultrasensitive Detection

The Simoa limit of detection is typically about a factor of 100 to 1000 times more sensitive than the traditional method of performing a protein assay—the enzyme-linked immunosorbent assay (ELISA) technique. It opens up the potential for being able to measure proteins at concentrations that have never been detected before in various kinds of samples including blood, which is the main focus for Simoa-based assays. However, challenges remain that there are certain biomolecules present in the blood at lower expression levels than what we can detect. Therefore, we are currently attempting to push the boundary of sensitivity to detect even lower concentrations using polymer science and nanotechnology. 

Catalytic Activity of Single Nanoparticles

Metal nanoparticles are important catalysts in a variety of industrial applications. However, their catalytic properties are not fully understood, as they are highly dependent on the details of particle structure, including shape, size, composition, and crystallinity. Using a method analogous to that described for single molecule enzyme activities, we can explore the individual catalytic activities of a heterogeneous ensemble of nanoparticles. The catalytic activities of hundreds of individual nanoparticles, as well as the detailed kinetics of the reactions, can be measured and statistically analyzed. These catalytic properties will be correlated with the optical and structural properties of the nanoparticles, via optical spectroscopy and scanning electron microscopy, respectively.

Point-of-Care Diagnostics

We are interested in developing a point-of-care diagnostic tool using the Simoa platform that is cost-effective and easy-to-use, specifically for the detection of post-translationally modified proteins relevant to Alzheimer’s Disease. A point-of-care device for specific and sensitive detection of protein biomarkers in blood including Tau, phosphorylated forms of Tau, and ABeta 42 is important for diagnosis, patient monitoring, and companion diagnostics in clinical trials. The project strategy includes exploring a simpler alternative to microwell arrays for bead immobilization and imaging. One approach is to immobilize beads in a monolithic hydrogel film; beads can be encapsulated in the hydrogel as it is formed in situ. This low-cost approach will allow for efficient loading, immobilization, and digital readout of beads for digital ELISA. We are also developing methods to localize the fluorescent signal on the beads in the hydrogel. Finally, we plan to create a method for imaging the beads using a simple device, such as a cell phone camera. These advances in the Simoa technology will lead to a simple and sensitive point-of-care device for clinicians to use in Alzheimer’s Disease diagnostics.