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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.

Lau HC, Lee IK, Ko PW, Lee HW, Huh JS, Cho WJ, Lim JO - PLoS ONE (2015)

Bottom Line: 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 cell-based biosensor significantly distinguished salivary sugar, trehalose of the AD group from the PD and control groups.

View Article: PubMed Central - PubMed

Affiliation: Biomedical Research Institute, Department of Biomedical Science, Kyungpook National University, Daegu, Korea.

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.

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Related in: MedlinePlus

EG-ISFET biosensor response currents of cells reacting to trehalose.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.
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pone.0117810.g004: EG-ISFET biosensor response currents of cells reacting to trehalose.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.

Mentions: The response generated by the EG-ISFET sensor using these cells was first examined using different concentrations of trehalose. As the concentration of trehalose increased, the sensing region, which contains the sensing cells, had a steep decrease in the current compared to the control cells on the reference region (Fig. 4). The observed current reduction might be because more hydroxide ions are being detected by the sensing cells. An exchange of ions occurs upon the binding of the sugar molecules to the gustatory receptors of Drosophila cells. These, in turn, alter the number of hydroxide ions available, and subsequently, cause a shift in the threshold voltage to the right, resulting in a reduction of the generated current. A minimum change in the current was observed with the control cells lacking the overexpression of the gustatory receptor Gr5a. These results indicate that the sensing cells responded efficiently to trehalose up to 0.001 M.


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.

Lau HC, Lee IK, Ko PW, Lee HW, Huh JS, Cho WJ, Lim JO - PLoS ONE (2015)

EG-ISFET biosensor response currents of cells reacting to trehalose.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.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4340960&req=5

pone.0117810.g004: EG-ISFET biosensor response currents of cells reacting to trehalose.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.
Mentions: The response generated by the EG-ISFET sensor using these cells was first examined using different concentrations of trehalose. As the concentration of trehalose increased, the sensing region, which contains the sensing cells, had a steep decrease in the current compared to the control cells on the reference region (Fig. 4). The observed current reduction might be because more hydroxide ions are being detected by the sensing cells. An exchange of ions occurs upon the binding of the sugar molecules to the gustatory receptors of Drosophila cells. These, in turn, alter the number of hydroxide ions available, and subsequently, cause a shift in the threshold voltage to the right, resulting in a reduction of the generated current. A minimum change in the current was observed with the control cells lacking the overexpression of the gustatory receptor Gr5a. These results indicate that the sensing cells responded efficiently to trehalose up to 0.001 M.

Bottom Line: 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 cell-based biosensor significantly distinguished salivary sugar, trehalose of the AD group from the PD and control groups.

View Article: PubMed Central - PubMed

Affiliation: Biomedical Research Institute, Department of Biomedical Science, Kyungpook National University, Daegu, Korea.

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.

Show MeSH
Related in: MedlinePlus