Non-invasive screening for Alzheimer's disease by sensing salivary sugar using Drosophila cells expressing gustatory receptor (Gr5a) immobilized on an extended gate ion-sensitive field-effect transistor (EG-ISFET) biosensor

PLoS One. 2015 Feb 25;10(2):e0117810. doi: 10.1371/journal.pone.0117810. eCollection 2015.

Abstract

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 Drosophila 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / diagnosis*
  • Animals
  • Biomarkers
  • Biosensing Techniques*
  • Carbohydrate Metabolism*
  • Case-Control Studies
  • Cell Line
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Female
  • Gene Expression*
  • Humans
  • Hydrogen-Ion Concentration
  • Male
  • Middle Aged
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism
  • Saliva / metabolism*
  • Sensitivity and Specificity
  • Trehalose / metabolism

Substances

  • Biomarkers
  • Drosophila Proteins
  • Receptors, Cell Surface
  • gustatory receptor, Drosophila
  • Trehalose

Grants and funding

This research was supported by the Converging Research Center Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2013K000364 and 2013K000372). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.