One Binder to Bind Them All

Abstract

High quality binders, such as antibodies, are of critical importance for chemical sensing applications. With synthetic alternatives, such as molecularly imprinted polymers (MIPs), less sensor development time and higher stability of the binder can be achieved. In this feature paper, I will discuss the impact of synthetic binders from an industrial perspective and I will challenge the molecular imprinting community on the next step to leapfrog the current status quo of MIPs for (bio)sensing. Equally important, but often neglected as an effective chemical sensor, is a good match of transducer and MIP coating for a respective application. To demonstrate an application-driven development, a biosensing use case with surface-imprinted layers on piezoacoustic sensors is reported. Depending on the electrode pattern for the transducer, the strong mechanical coupling of the analyte with the MIP layer coated device allows the adoption of the sensitivity from cell mass to cell viability with complete reversibility.

Keywords: aptamers; binder; cells; environment; healthcare; life science; lithography; molecularly imprinted polymers; quartz crystal microbalance; receptor; sensor.

Figure 1

Schematic illustration of the quartz crystal microbalance (QCM) layouts with reference and sensitive electrodes (yellow) covered with a polyurethane thin film (green). The reference electrode is coated with a plane non-imprinted thin film and the sensitive electrode is coated with the surface-imprinted layer. (a) Traditional layout with smaller electrodes (broken line) towards the gaseous phase. (b) Cross-section of the sensitive layer. With larger electrodes on ground, facing the aqueous phase, the electrical fringe fields (broken lines) are pulled into the crystal. (c) QCM layout with a grid electrode facing the aqueous phase. (d) Cross-section showing schematic fringe fields at the edges of the grid electrode.

Figure 2

Schematic illustrations of the MIP layer mediated resonant coupling effects between (I) large viable yeast cells, (II) non-viable cells, (III) viable cells matching the mould, (IV) budding yeast cells, and (V) small cells and the transducer. (a,b) Mass-sensitive effects with conventional electrodes are related to the growth stage of the yeast cells and their viability. The electrode geometry allows excluding capacitive coupling to the medium. Without sufficient geometrical fit, the mass sensitivity for cells larger than the imprint (I) reduces. Non-viable cells with smaller diameter (II) show perfect fit in the moulded pits and ideal mechanical coupling to the MIP layer. (c,d) The additional fringe fields with grid electrodes allow probing of the dielectric properties of yeast cells and diminishes the gravimetric response.

Figure 3

Superimposed differential measurements with a conventional QCM electrode layout for high S. cerevisiae suspensions in PBS buffer with 100% viable cells (blue) and non-viable cells (red).

Figure 4

Differential sensor response with a S. cerevisiae imprinted layer on a grid electrode. All samples had a constant cell concentration of 10⁷ cells/mL. Gravimetric and non-gravimetric responses are observed depending on the cell viability. The area under the response curve is colored in yellow to guide the eye.

Figure 5

Differential sensor response with a S. cerevisiae imprinted layer on a grid electrode with an increasing concentration of NaCl in phosphate-buffered saline (PBS). All samples had a constant cell concentration of 10⁷ cells/mL. Non-gravimetric responses are observed independent on the buffer conductivity. Increasing conductance causes a pseudo-gravimetric response due to capacitive coupling of the medium. The area under the response curve is colored in red for viable and blue for non-viable cells to guide the eye.