Multiplexed microneedle-based biosensor array for characterization of metabolic acidosis

Abstract

The development of a microneedle-based biosensor array for multiplexed in situ detection of exercise-induced metabolic acidosis, tumor microenvironment, and other variations in tissue chemistry is described. Simultaneous and selective amperometric detection of pH, glucose, and lactate over a range of physiologically relevant concentrations in complex media is demonstrated. Furthermore, materials modified with a cell-resistant (Lipidure(®)) coating were shown to inhibit macrophage adhesion; no signs of coating delamination were noted over a 48-h period.

Figure 1

Scanning electron micrograph of a single microneedle (A) and schematic of the microneedle-biosensor assembly (B).

Figure 2

Calibration curves of a chemically modified carbon paste electrode in 0.1 M phosphate buffer (pH 5.0-8.0 at 0.5 intervals) against an outside Ag/AgCl and Pt reference and counter electrode, respectively.

Figure 3

Calibration curves of carbon paste containing glucose oxidase in 0.1 M phosphate buffer (pH 5.0, 6.0, 7.0 and 7.5 are indicated by a, b, c, and d, respectively) against an outside Ag/AgCl and Pt reference and counter electrodes with a detection potential of -0.05 V. Data were obtained from the current response after 5 seconds.

Figure 4

Calibration curves of carbon paste-containing lactate oxidase in 0.1 M phosphate buffer (pH 5.0, 6.0, 7.0 and 7.5 are indicated by a, b, c, and d, respectively) against an outside Ag/AgCl and Pt reference and counter electrode with a detection potential of -0.15 V.

Figure 5

Selectivity of the lactate electrode. Figure shows three scans in the order of a blank solution, 4 mM glucose, and 4 mM lactate. Inset: Cyclic voltammogram of Fast Blue-modified carbon paste microneedle.

Figure 6

Selectivity of the glucose electrode.

Figure 7

Fluorescent images of macrophage adhesion to uncoated and Lipidure®-coated E-shell 300 acrylate-based polymer at 2 and 24 hours post seeding (200 μm scale bar).