Macromolecular Amplification of Binding Response in Superaptamer Hydrogels

Abstract

It is becoming more important to detect ultralow concentrations of analytes for biomedical, environmental, and national security applications. Equally important is that new methods should be easy to use, inexpensive, portable, and if possible allow detection by the naked eye. By and large, detection of low concentrations of analytes cannot be achieved directly but requires signal amplification by catalysts, macromolecules, metal surfaces, or supramolecular aggregates. The rapidly progressing field of macromolecular signal amplification has been advanced using conjugated polymers, chirality in polymers, solvating polymers, and polymerization/depolymerization strategies. A new type of aptamer-based hydrogel with specific response to target proteins presented in this report demonstrates an additional category of macromolecular signal amplification. This superaptamer assembly provides the first example of using protein-specific aptamers to create volume-changing hydrogels with amplified response to the target protein. A remarkable aspect of these superaptamer hydrogels is that volume shrinking is visible to the naked eye down to femtomolar concentrations of protein. This extraordinary macromolecular amplification is attributed to a complex interplay between protein-aptamer supramolecular cross-links and the consequential reduction of excluded volume in the hydrogel. Specific recognition is even maintained in biological matrices such as urine and tears. Furthermore, the gels can be dried for long-term storage and regenerated for use without loss of activity. In practice, the ease of this biomarker detection method offers an alternative to traditional analytical techniques that require sophisticated instrumentation and highly trained personnel.

Molecularly Imprinted Polymers with Stimuli-Responsive Affinity: Progress and Perspectives

“…Besides these commonly used methods, some novel strategies have been reported to prepare responsive MIP. Bai et al prepared a new type of aptamer-based hydrogel with specific response to target proteins [86]. The volume shrinking of the superaptamer hydrogels is visible to the naked eye in response to femtomolar concentrations of protein ( Figure 9).…”

Aptamer-Based Hydrogels and Their Applications

“…A new type of aptamer-based hydrogel was developed for specific, ultrasensitive, and visual detection of proteins [124]. The remarkable feature of this kind of 2+ concentrations with range from 10 nM to 100 μM.…”

“…Reprinted with the permission from Ref. [124]. Copyright 2013 American Chemical Society femtomolar range.…”

Molecularly Imprinted Polymers with DNA Aptamer Fragments as Macromonomers

“…17,18 DNA aptamers are obtained from combinatorial selections and they can be evolved to bind many target molecules. 19,20 Incorporation of full-length aptamers in MIPs was previously reported for thrombin binding, 21 and recently for prostate specific antigen via terminal acrydite modification of the aptamers. 22 Acrylamidemodified uridines were incorporated into the cocaine aptamer, so that polymerization took place at multiple positions along the aptamer chain.…”