Portable Quartz Crystal Resonator Sensor for Characterising the Gelation Kinetics and Viscoelastic Properties of Hydrogels

Abstract

Hydrogel biomaterials have found use in various biomedical applications partly due to their biocompatibility and tuneable viscoelastic properties. The ideal rheological properties of hydrogels depend highly on the application and should be considered early in the design process. Rheometry is the most common method to study the viscoelastic properties of hydrogels. However, rheometers occupy much space and are costly instruments. On the other hand, quartz crystal resonators (QCRs) are devices that can be used as low-cost, small, and accurate sensors to measure the viscoelastic properties of fluids. For this reason, we explore the capabilities of a low-cost and compact QCR sensor to sense and characterise the gelation process of hydrogels while using a low sample amount and by sensing two different crosslink reactions: covalent bonds and divalent ions. The gelation of covalently crosslinked mucin hydrogels and physically crosslinked alginate hydrogels could be monitored using the sensor, clearly distinguishing the effect of several parameters affecting the viscoelastic properties of hydrogels, including crosslinking chemistry, polymer concentrations, and crosslinker concentrations. QCR sensors offer an economical and portable alternative method to characterise changes in a hydrogel material's viscous properties to contribute to this type of material design, thus providing a novel approach.

Keywords: covalently crosslinked hydrogels; hydrogel kinetics characterisation; physically crosslinked hydrogels; quartz crystal resonator.

Figure A1

EDC NHS coupling (tetrazine).

Figure A2

EDC NHS coupling (norbornene).

Figure A3

EDC NHS coupling (simplified).

Figure A4

Reaction mechanism Inverse electron demand Diels–Alder.

Figure 1

Characterisation of muc-gel formation. Using ViSQCT sensor @ 10MHz. (a) Comparison of $\Delta f$ reached at the plateaulike stage after 25 min for 15 and 25 mg/mL muc-gels. (b) Time-dependent evaluation of $\Delta f$ and $\Delta \mathrm{\Gamma }$ for 15 mg/mL muc-gels. (c) Time-dependent evaluation of $\Delta f$ and $\Delta \mathrm{\Gamma }$ for 25 mg/mL muc-gels. The shaded area denotes the standard deviation as obtained from measurements of n = 3 independent samples. Rheological characterisation: (d) Time-dependent rheological evaluation for 15 mg/mL and (e) 25 mg/mL muc-gels. Rheological data were taken with permission from previously published work [3].

Figure 2

Comparison between rheological evaluation and complex modulus obtained from $\Delta f$ and $\Delta \mathrm{\Gamma }$. (left) 15 mg/mL muc-gel; (right) 25 mg/mL muc-gel.

Figure 3

(left) $\Delta f$ and $\Delta \mathrm{\Gamma }$ changes after placing an alginate solution (15 mg/mL) on the sensor. Gelation was performed once the signal had stabilised. (right) $\Delta f$ and $\Delta \mathrm{\Gamma }$ change likely caused by a dilution effect following the exposure of the alginate to a solution of NaCl (0.4 M). The shaded area denotes the standard deviation as obtained from measurements of n = 3 independent samples.

Figure 4

(a) Structure of alginate reacting with ${\mathrm{Ca}}^{2+}$ and ${\mathrm{Ba}}^{2+}$. Characterisation of alginate gel formation using two drivers with two concentrations using ViSQCT sensor @ 10 MHz. Time-dependent evaluation of $\Delta f$ and $\Delta \mathrm{\Gamma }$: (b) ${\mathrm{CaCl}}_2$ (0.4 M). (c) ${\mathrm{BaCl}}_2$ (0.4 M). (d) ${\mathrm{CaCl}}_2$ (0.2 M). (e) ${\mathrm{BaCl}}_2$ (0.2 M). The shaded area denotes the standard deviation obtained from measurements of n = 3 independent samples. (f) Comparison of $\Delta f$ plateaulike stage for the four cases.

Figure 5

Tetrazine (Tz) and norbornene (Nb) conjugated to BSM and the crosslinking reaction [28].

Figure 6

Egg-box model that illustrates the sizes of Ca²⁺ and Ba²⁺ ions that formed an ionic coordination with alginate.

Figure 7

Experimental setup to measure hydrogel gelation process.