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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

Effect of the pH on the sensitivity of SnO2 membrane.The reference voltage (V) is shown as a function of pH evaluated at a reference current of 100 μA.
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pone.0117810.g002: Effect of the pH on the sensitivity of SnO2 membrane.The reference voltage (V) is shown as a function of pH evaluated at a reference current of 100 μA.

Mentions: Prior to performing the measurement using cells, we determined the pH sensitivity and chemical stability of the EG-ISFET sensor device. The EG-ISFET with the SnO2 membrane showed a pH sensitivity of 51.15 mV/pH and a linearity of 99.93% (Fig. 2). The pH sensitivity of the SnO2 sensing membrane we used in this study is very close to the Nernstian limit of 59 mV/pH. This suggests a high sensitivity of the EG-ISFET sensor. The drift rate of the membrane was found to be 2.63 mV/h indicates excellent stability of the sensor device (Fig. 3). We found that the pH sensitivity and stability of the SnO2 sensing membrane are important factors for the efficiency, stability, and sensitivity of the sensor. After this quality check, the cells can be applied and the sensor can be used as a cell-based biosensor. We have previously fabricated a cell-based ISFET sensor by using a silicon oxide-based membrane. This setup also showed good sensitivity [32]. However, the EG-ISFET sensor, fabricated using the SnO2 membrane described in this study, had a higher pH sensitivity and stability than the previous design. These results demonstrate that this improved EG-ISFET sensor is more efficient than the previous design.


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)

Effect of the pH on the sensitivity of SnO2 membrane.The reference voltage (V) is shown as a function of pH evaluated at a reference current of 100 μA.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0117810.g002: Effect of the pH on the sensitivity of SnO2 membrane.The reference voltage (V) is shown as a function of pH evaluated at a reference current of 100 μA.
Mentions: Prior to performing the measurement using cells, we determined the pH sensitivity and chemical stability of the EG-ISFET sensor device. The EG-ISFET with the SnO2 membrane showed a pH sensitivity of 51.15 mV/pH and a linearity of 99.93% (Fig. 2). The pH sensitivity of the SnO2 sensing membrane we used in this study is very close to the Nernstian limit of 59 mV/pH. This suggests a high sensitivity of the EG-ISFET sensor. The drift rate of the membrane was found to be 2.63 mV/h indicates excellent stability of the sensor device (Fig. 3). We found that the pH sensitivity and stability of the SnO2 sensing membrane are important factors for the efficiency, stability, and sensitivity of the sensor. After this quality check, the cells can be applied and the sensor can be used as a cell-based biosensor. We have previously fabricated a cell-based ISFET sensor by using a silicon oxide-based membrane. This setup also showed good sensitivity [32]. However, the EG-ISFET sensor, fabricated using the SnO2 membrane described in this study, had a higher pH sensitivity and stability than the previous design. These results demonstrate that this improved EG-ISFET sensor is more efficient than the previous design.

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