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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

Top view image of the EG-ISFET sensor device.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.
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pone.0117810.g001: Top view image of the EG-ISFET sensor device.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.

Mentions: As an improvement on the design of the conventional ISFET, our biosensor makes use of the extensible gate terminal of MOSFET to allow construction of two independent components: one used for reference and the other used for sensing (Fig. 1). These components are essential to obtaining accurate measurements. Because of this unique design, the responses from the patient and control groups can be generated and observed concurrently.


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)

Top view image of the EG-ISFET sensor device.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.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0117810.g001: Top view image of the EG-ISFET sensor device.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.
Mentions: As an improvement on the design of the conventional ISFET, our biosensor makes use of the extensible gate terminal of MOSFET to allow construction of two independent components: one used for reference and the other used for sensing (Fig. 1). These components are essential to obtaining accurate measurements. Because of this unique design, the responses from the patient and control groups can be generated and observed concurrently.

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