Sensing area in the Rotello Research Group focuses on the design and development of biosensor using nanomaterials for a broad range of analytes: proteins, bacteria and cancer cells. Most biomolecular recognition processes in biology occur via specific interactions. However, sensory processes in mammalians, such as taste and smell, use “differential” binding through pattern recognition technique. Here, the taste/smell receptors bind to the analytes by different binding characteristics that are selective rather than specific. This pattern recognition sensing approach is known as “chemical nose/tongue” sensing.

    Chemical nose sensing employs the selective interactions of nanoparticle-based sensor array and the analyte mixtures. Combined responses from the sensor array create a characteristic pattern, much similar to a fingerprint for each analyte. Therefore, none of the chemical nose sensors need to be highly specific for any given analyte. These fingerprints can be analyzed statistically for the identification of individual target analytes, as well as complex mixtures using linear discriminant analysis (LDA).

    Schematic illustration for chemical nose sensor. Distinct patterns of analytes were generated based on different binding affinity of analytes toward sensor array. These patterns are processed by multivariant analysis methods. The matrix data’s dimensionalities can be reduced to non-overlapping clusters for easier visualization.

    In the Rotello Research Group, gold nanoparticles (AuNPs) with the excellent surface tunability are used for the chemical nose sensing strategy. Direct transduction of the binding of AuNPs to analytes is challenging. However, AuNPs feature strong quenching ability. This photophysical property enables the use of fluorescent displacement assays, where displacement of a fluorophore from AuNPs signals the binding event.

    In our initial study, a sensor array containing non-covalent gold nanoparticle-fluorescent polymer assemblies was created to identify and quantify protein, 
bacteria, and cancerous cells. The polymer fluorescence is quenched by gold nanoparticles, whereas proteins, bacteria, or cancerous cells disrupt the nanoparticle-polymer interaction producing distinct fluorescence response patterns

    Schematic illustration for chemical nose sensor. A) Schematic of array-based sensing of biomacromolecules using displacement of conjugated polymer reporter groups. B) Schematic of the distinct fluorescence response patterns for analytes. C) Canonical score plot by LDA for the first two factors of simplified fluorescence response patterns obtained with NP-PPE assembly arrays against i) proteins, ii) bacteria, and iii) mammalian cells (95% confidence ellipses shown).

    In our ongoing studies, we are exploiting both new alternative approaches for protein, bacteria, and cancerous cells detection and new data analysis strategies to apply this methodology to more complex matrices featuring a large diversity of target analytes.

    Selected References:

    1) De, M.; Rana, S.; Akpinar, H.; Miranda, O. R.; Arvizo, R. R.; Bunz, U. H. F.; Rotello, V. M. “Sensing of Proteins in Human Serum Using Conjugates of Nanoparticles and Green Fluorescent Protein” Nat. Chem. 2009, 1, 461-465.
    2) Bajaj, A.; Miranda, O. R.; Kim, I.-B.; Phillips, R. L.; Jerry, D. J.; Bunz, U. H. F.; Rotello, V. M. “Detection and Differentiation of Normal, Cancerous, and Metastatic Cells Using Nanoparticle-polymer Sensor Arrays” Proc. Nat. Acad. Sci. U.S.A. 2009, 106, 10912-10916.
    3) Rana, S.; Singla, A. K.; Bajaj, A.; Elci, S. G.; Miranda, O.; Mout, R.; Yan, B. Jirik, F. R.; Rotello, V. M. “Array-Based Sensing of Metastatic Cells and Tissues Using Nanoparticle-Fluorescent Protein Conjugates” ACS Nano 2012, 6, 8233-8240.