MOLECULARLY IMPRINTED SUPER-APTAMER HYDROGELS FOR RNA AND DNA BIOSENSORS

We have recently reported aptamer-based bioimprinted hydrogels exhibiting a visible volume shrinking response to target protein biomarkers down to the femtomolar to millimolar concentration range [1,2]. 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 the case of the virus imprinted gels, the visual assessment is enhanced by micromolding the virus-imprinted hydrogel on a diffraction grating to form the first “double-imprinted” film with an optical diffraction output. In this presentation a new hydrogel sensor system was developed for a DNA mimic of the RNA biomarker mir21, a 22 base pair sequence that has been linked to colon and breast cancer. Initial investigation using a capillary imprinted hydrogel system was optimized to give 5.7 % shrinkage of the gel only when exposed to the mir21 biomarker mimic. In addition, a new approach to the hydrogel imprinting was employed using thiol-ene polymer lithographic molds. The thiol-ene composite material is more hydrophilic which allowed for the effective and reproducible transfer of the pattern versus historically used PDMS stamps. The diffraction hydrogels displayed similar results to the capillary hydrogels with a 4.2 % response to the DNA mir21 target. The limit of detection by these imprinted hydrogels is comparable to other sensor methods.

Scheme 1 Shrinking mechanism of DNA mir21 imprinted hydrogels in response to the DNA mir21 target.

References

[1] Bai, Wei; Spivak, David A. “A Double-Imprinted Diffraction-Grating Sensor Based on a Virus-Responsive Super-Aptamer Hydrogel Derived from an Impure Extract”; Angewandte Chemie International Edition, 2014, 53, 2095–2098.

[2] Bai, Wei; Gariano, Nicholas A.; Spivak, David A. “Macromolecular Amplification of Binding Response in Superaptamer Hydrogels”, Journal of the American Chemical Society 2013, 135, 6977-6984.