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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

Change in EG-ISFET biosensor current for AD and PD saliva samples.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). *p ≤ 0.05.
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pone.0117810.g007: Change in EG-ISFET biosensor current for AD and PD saliva samples.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). *p ≤ 0.05.

Mentions: After obtaining stable and reliable results using trehalose, the EG-ISFET biosensor was then used to detect the change of response to saliva samples collected from patient and control groups. The saliva samples of the control group resulted in a higher change in the current than the AD (Fig. 5) and PD groups (Fig. 6). The control group in Fig. 6 had a response current of 0.078 whereas the current for PD group was 0.016. Although the difference was small, the response current of control group was still higher than the PD group. After the values were normalized to the control group, the PD group was found to have higher change of current compared to the AD group (Fig. 7). We found a statistically significant difference between the AD and the other two groups.


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)

Change in EG-ISFET biosensor current for AD and PD saliva samples.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). *p ≤ 0.05.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0117810.g007: Change in EG-ISFET biosensor current for AD and PD saliva samples.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). *p ≤ 0.05.
Mentions: After obtaining stable and reliable results using trehalose, the EG-ISFET biosensor was then used to detect the change of response to saliva samples collected from patient and control groups. The saliva samples of the control group resulted in a higher change in the current than the AD (Fig. 5) and PD groups (Fig. 6). The control group in Fig. 6 had a response current of 0.078 whereas the current for PD group was 0.016. Although the difference was small, the response current of control group was still higher than the PD group. After the values were normalized to the control group, the PD group was found to have higher change of current compared to the AD group (Fig. 7). We found a statistically significant difference between the AD and the other two groups.

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