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Direct determination of a small-molecule drug, valproic Acid, by an electrically-detected microcantilever biosensor for personalized diagnostics.

Huang LS, Gunawan C, Yen YK, Chang KF - Biosensors (Basel) (2015)

Bottom Line: The measured surface stresses showed a profile over a concentration range of 50-500 μg·mL-1, which covered the clinically therapeutic range of 50-100 μg·mL-1.The estimated limit of detection (LOD) was calculated to be 45 μg·mL-1, and the binding affinity between the drug and the antibody was measured at around 90 ± 21 μg·mL-1.Lastly, the results of the proposed device showed a similar profile in valproic acid drug detection with those of the clinically-used fluorescence polarization immunoassay.

View Article: PubMed Central - PubMed

Affiliation: Institute of Applied Mechanics, National Taiwan University, Taipei 10617, Taiwan. lshuang@ntu.edu.tw.

ABSTRACT
Direct, small-molecule determination of the antiepileptic drug, valproic acid, was investigated by a label-free, nanomechanical biosensor. Valproic acid has long been used as an antiepileptic medication, which is administered through therapeutic drug monitoring and has a narrow therapeutic dosage range of 50-100 μg·mL-1 in blood or serum. Unlike labeled and clinically-used measurement techniques, the label-free, electrical detection microcantilever biosensor can be miniaturized and simplified for use in portable or hand-held point-of-care platforms or personal diagnostic tools. A micromachined microcantilever sensor was packaged into the micro-channel of a fluidic system. The measurement of the antiepileptic drug, valproic acid, in phosphate-buffered saline and serum used a single free-standing, piezoresistive microcantilever biosensor in a thermally-controlled system. The measured surface stresses showed a profile over a concentration range of 50-500 μg·mL-1, which covered the clinically therapeutic range of 50-100 μg·mL-1. The estimated limit of detection (LOD) was calculated to be 45 μg·mL-1, and the binding affinity between the drug and the antibody was measured at around 90 ± 21 μg·mL-1. Lastly, the results of the proposed device showed a similar profile in valproic acid drug detection with those of the clinically-used fluorescence polarization immunoassay.

No MeSH data available.


(a) A double sodium dodecyl sulfate polyacrylamide gel electrophoresis(dSDS-PAGE) for capture antibody; (b) detection of various valproic acid concentrations and the test of non-specific binding with another drug, phenytoin.
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biosensors-05-00037-f003: (a) A double sodium dodecyl sulfate polyacrylamide gel electrophoresis(dSDS-PAGE) for capture antibody; (b) detection of various valproic acid concentrations and the test of non-specific binding with another drug, phenytoin.

Mentions: As shown in Figure 3a, the light chain denotes the molecular weight of 25 kDa distributed 5.6–6.6 in pI values, and the heavy chain with the molecular weight of 50 kDa exhibited 6.4–7.2 in its pI values. As a result of the dSDS-PAGE, the range of valproic acid antibody macromolecules was simply shown to be 5.6–7.2. To obtain opposite charges for the drug and antibody, the pH environment of the PBS solution was set at pH 5. Both the antibody and drug molecules exhibited opposite charges for attraction to enhance the binding capability of the microcantilever biosensors. Meanwhile, the antibody and the antiepileptic drug, valproic acid, respectively carried negative and positive charges in solution.


Direct determination of a small-molecule drug, valproic Acid, by an electrically-detected microcantilever biosensor for personalized diagnostics.

Huang LS, Gunawan C, Yen YK, Chang KF - Biosensors (Basel) (2015)

(a) A double sodium dodecyl sulfate polyacrylamide gel electrophoresis(dSDS-PAGE) for capture antibody; (b) detection of various valproic acid concentrations and the test of non-specific binding with another drug, phenytoin.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4384081&req=5

biosensors-05-00037-f003: (a) A double sodium dodecyl sulfate polyacrylamide gel electrophoresis(dSDS-PAGE) for capture antibody; (b) detection of various valproic acid concentrations and the test of non-specific binding with another drug, phenytoin.
Mentions: As shown in Figure 3a, the light chain denotes the molecular weight of 25 kDa distributed 5.6–6.6 in pI values, and the heavy chain with the molecular weight of 50 kDa exhibited 6.4–7.2 in its pI values. As a result of the dSDS-PAGE, the range of valproic acid antibody macromolecules was simply shown to be 5.6–7.2. To obtain opposite charges for the drug and antibody, the pH environment of the PBS solution was set at pH 5. Both the antibody and drug molecules exhibited opposite charges for attraction to enhance the binding capability of the microcantilever biosensors. Meanwhile, the antibody and the antiepileptic drug, valproic acid, respectively carried negative and positive charges in solution.

Bottom Line: The measured surface stresses showed a profile over a concentration range of 50-500 μg·mL-1, which covered the clinically therapeutic range of 50-100 μg·mL-1.The estimated limit of detection (LOD) was calculated to be 45 μg·mL-1, and the binding affinity between the drug and the antibody was measured at around 90 ± 21 μg·mL-1.Lastly, the results of the proposed device showed a similar profile in valproic acid drug detection with those of the clinically-used fluorescence polarization immunoassay.

View Article: PubMed Central - PubMed

Affiliation: Institute of Applied Mechanics, National Taiwan University, Taipei 10617, Taiwan. lshuang@ntu.edu.tw.

ABSTRACT
Direct, small-molecule determination of the antiepileptic drug, valproic acid, was investigated by a label-free, nanomechanical biosensor. Valproic acid has long been used as an antiepileptic medication, which is administered through therapeutic drug monitoring and has a narrow therapeutic dosage range of 50-100 μg·mL-1 in blood or serum. Unlike labeled and clinically-used measurement techniques, the label-free, electrical detection microcantilever biosensor can be miniaturized and simplified for use in portable or hand-held point-of-care platforms or personal diagnostic tools. A micromachined microcantilever sensor was packaged into the micro-channel of a fluidic system. The measurement of the antiepileptic drug, valproic acid, in phosphate-buffered saline and serum used a single free-standing, piezoresistive microcantilever biosensor in a thermally-controlled system. The measured surface stresses showed a profile over a concentration range of 50-500 μg·mL-1, which covered the clinically therapeutic range of 50-100 μg·mL-1. The estimated limit of detection (LOD) was calculated to be 45 μg·mL-1, and the binding affinity between the drug and the antibody was measured at around 90 ± 21 μg·mL-1. Lastly, the results of the proposed device showed a similar profile in valproic acid drug detection with those of the clinically-used fluorescence polarization immunoassay.

No MeSH data available.