Array-based "Chemical Nose" Sensing in Diagnostics and Drug Discovery

Abstract

Array-based sensor "chemical nose/tongue" platforms are inspired by the mammalian olfactory system. Multiple sensor elements in these devices selectively interact with target analytes, producing a distinct pattern of response and enabling analyte identification. This approach offers unique opportunities relative to "traditional" highly specific sensor elements such as antibodies. Array-based sensors excel at distinguishing small changes in complex mixtures, and this capability is being leveraged for chemical biology studies and clinical pathology, enabled by a diverse toolkit of new molecular, bioconjugate and nanomaterial technologies. Innovation in the design and analysis of arrays provides a robust set of tools for advancing biomedical goals, including precision medicine.

Keywords: array-based sensing; biomedicine; cancer cell detection; diagnosis; protein detection.

Figure 1.

An overview of chemical nose sensing – moving beyond N receptors for N analytes. (a) A traditional specific sensor and (b) a cross-reactive (but still selective) array-based sensor. In (a) one element can interact with one analyte transducing single responses with N receptors needed to measure N analytes. For (b), each element in a mixture interacts in different ways with a cross-reactive array. The transduction of the interactions leads to pattern generation for the combination of elements. The patterns are then processed, and it is possible to detect more analytes than there are elements.

Figure 2.

Protein detection in serum using array-based sensors. (a) Structure of cationic Au-NPs. (b) Sensing scheme of AuNP-GFP array with serum proteins, where the addition of proteins causes differential release of GFP. (c) Differentiation of five major serum proteins in spiked human serum samples. Adapted with permission from Reference [57]. Copyright 2009 Nature Publishing Group

Figure 3.

Demonstration of the use of fluorescent gold nanoclusters derived from collagen (Col) and Macerozyme-10 (Mac) in protein sensing. (a) Differential changes in optical signals upon interaction with target proteins in aqueous solution - lysozyme (Lys), human serum albumin (HSA), egg white albumin (EA), pepsin (Pep), hemoglobin (Hb), trypsin (Try), catalase (CAT), and transferrin (Tf). (b) Fluorescence emission shifts in both intensity and wavelength upon binding with select proteins. Adapted with permission from Reference [58]. Copyright 2014 American Chemical Society.

Figure 4.

Discrimination of proteins using a multifunctional small molecule bearing responsive fluorophores. (a) Schematic illustration of sensor construction. 3 protein binding moieties (EA- ethacrynic amide, MT – marimastat and Apt – a DNA aptamer) and 4 fluorophores (indicated by *s – nitrobenzoxadiazole, nile red, cyanine 5.5 and cyanine 7) were added to a cis-amino proline scaffold to form the sensor. (b) Fluorescence patterns generated by sensors after adding tested proteins. (c) LDA classification of enriched proteins in urine samples for different glutathione-S-transferases (GSTs), matrix metalloproteases (MMPs) and platelet-derived growth factors (PDGFs). Adapted from Reference [64]. Copyright 2017 Nature Publishing Group.

Figure 5.

Liver fibrosis diagnosis using array-based sensing strategy. (a) Schematic illustration of polymer-based array sensing for serum proteome to distinguish between fibrotic and nonfibrotic patients. (b) Polymer structure featuring three responsive fluorophores. (c) Potential working principle of environmental polymers. Adapted with permission from Reference [68]. Copyright 2017 Wiley-VCH.

Figure 6.

Breast cancer cell line sensing with gold nanoclusters. (a) Schematic illustration of the dual-ligand functionalized gold nanoclusters sensor array. (a) (b) LDA classification of 10 breast cancer cell lines. Adapted with permission from Reference [72]. Copyright 2018 Elsevier.

Figure 7.

The use of array-based sensor in profiling drug mechanisms of chemotherapeutics. (a) Complexation of sensor array. (b) Workflow for drug screening using nanoparticle-based arrays. (c) Classification of 7 different drug mechanisms. Adapted with permission from Reference [78]. Copyright 2015 Nature Publishing Group.