Effect of the pH on the sensitivity of SnO₂ membrane.

<p>The reference voltage (V) is shown as a function of pH evaluated at a reference current of 100 μA.</p

Drift rate of SnO₂ membrane in a solution with pH 7.

<p>The reference voltage (V) is shown as a function of pH evaluated at a reference current of 100 μA.</p

Change in EG-ISFET biosensor currents for AD and control saliva samples.

<p>The change of current generated from the AD and control groups. Data are presented as median. *<i>p</i> ≤ 0.05.</p

Top view image of the EG-ISFET sensor device.

<p>The EG-ISFET sensor consists of an independent reference and sensing region for simultaneous measurements of samples from patient and control groups. A commercially available transistor (MC14007UBCP) was used as the MOSFET part of the sensor. The gate terminal of both sensing and reference regions was segregated from the conventional ISFET device. A SnO₂ membrane was deposited on the gate terminal of the EG-ISFET sensor and used as the sensing membrane. Response currents generated were measured using a Hewlett-Packard 4156B High-Precision Semiconductor Parameter Analyzer.</p

Non-Invasive Screening for Alzheimer’s Disease by Sensing Salivary Sugar Using <i>Drosophila</i> Cells Expressing Gustatory Receptor (Gr5a) Immobilized on an Extended Gate Ion-Sensitive Field-Effect Transistor (EG-ISFET) Biosensor

<div><p>Body fluids are often used as specimens for medical diagnosis. With the advent of advanced analytical techniques in biotechnology, the diagnostic potential of saliva has been the focus of many studies. We recently reported the presence of excess salivary sugars, in patients with Alzheimer’s disease (AD). In the present study, we developed a highly sensitive, cell-based biosensor to detect trehalose levels in patient saliva. The developed biosensor relies on the overexpression of sugar sensitive gustatory receptors (Gr5a) in <i>Drosophila</i> cells to detect the salivary trehalose. The cell-based biosensor was built on the foundation of an improved extended gate ion-sensitive field-effect transistor (EG-ISFET). Using an EG-ISFET, instead of a traditional ion-sensitive field-effect transistor (ISFET), resulted in an increase in the sensitivity and reliability of detection. The biosensor was designed with the gate terminals segregated from the conventional ISFET device. This design allows the construction of an independent reference and sensing region for simultaneous and accurate measurements of samples from controls and patients respectively. To investigate the efficacy of the cell-based biosensor for AD screening, we collected 20 saliva samples from each of the following groups: participants diagnosed with AD, participants diagnosed with Parkinson’s disease (PD), and a control group composed of healthy individuals. We then studied the response generated from the interaction of the salivary trehalose of the saliva samples and the Gr5a in the immobilized cells on an EG-ISFET sensor. The cell-based biosensor significantly distinguished salivary sugar, trehalose of the AD group from the PD and control groups. Based on these findings, we propose that salivary trehalose, might be a potential biomarker for AD and could be detected using our cell-based EG-ISFET biosensor. The cell-based EG-ISFET biosensor provides a sensitive and direct approach for salivary sugar detection and may be used in the future as a screening method for AD.</p></div

EG-ISFET biosensor response currents of cells reacting to trehalose.

<p>The change of current determined with the EG-ISFET sensor is represented as a function of trehalose concentration. The sensing cells depicted as closed red squares, whereas the control cells are shown as closed blue circles.</p

Demographic and clinical data of the study participants.

<p>Values are represented as mean ± SD. MMSE scores range from 0 (severe impairment) to 30 (no impairment). A score of higher than 27 was considered normal. CDR-SOB scores range from 0 (cognitive normality) to 18 (maximal cognitive impairment). Hoehn and Yahr (H-Y) scores range from stage 1 (mild) to stage 5 (maximal disabling). The <i>p</i>-value that evaluates statistical significance between these variables was computed using the one-way ANOVA.</p><p>Demographic and clinical data of the study participants.</p

Change in EG-ISFET biosensor current for AD and PD saliva samples.

<p>The change of current generated from the AD and PD groups after the values were normalized to the values obtained from the control group of healthy individuals. Values are represented as median (left). *<i>p</i> ≤ 0.05.</p