Noninvasive Sialic Acid Detection at Cell Membrane by Using Phenylboronic Acid Modified Self-Assembled Monolayer Gold Electrode

Abstract

Alternations of sialic acid (SA) content on cell surface glycan chains have been implicated in numerous normal and pathological processes including developments, differentiations, and tumor metastasis. Overexpressions of SA have been implicated in the malignant and metastatic phenotypes for many different types of cancers, while decreased SA expression has also been identified in erythrocytes of diabetic mellitus. Techniques to conveniently monitor cell surface SA would therefore have great relevance to cytology. Preexisting methodologies to quantify SA, however, involve multiple enzymatic, dye-labeling, and lethal procedures, which are costly and time-consuming. Here we developed a potentiometric SA detection using a phenylboronic acid (PBA) compound integrated into the form of a self-assembled monolayer (SAM) onto a field effect transistor (FET) extended gold gate electrode. Due to selective binding between undisassociated PBA and SA at pH 7.4 among other glycan chain constituent monosaccharides, we found that carboxyl anions of SA were exclusively detectable as the change in threshold voltage (V(T)) of the PBA-modified FET. The technique was applied to analyses of altered SA expressions on rabbit erythrocyte as a model for diabetes. Comparative SA expression analyses for each healthy and diseased model revealed that the disease could be feasibly diagnosed simply by placing the known-count cell suspensions onto the device without any labeling and enzymatic procedures. Such a technique may also provide a quantitative adjunct to histological evaluation of tumor malignancy and metastatic potential during intra- and postoperative diagnoses. Also advantageously, a technique herein described is all within a CMOS (Complementary Metal Oxide Semiconductor) compatible format thus promising for highly efficient and low cost manufacturing with readiness of downsizing and integration by virtue of advanced semiconductor processing technologies.