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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.


The measured results of 100 μg·mL−1 valproic acid in PBS, 50% serum and pure serum.
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biosensors-05-00037-f005: The measured results of 100 μg·mL−1 valproic acid in PBS, 50% serum and pure serum.

Mentions: Figure 5 shows the signals responses for the detection of 100 µg·mL−1 valproic acid drug in three solutions of PBS, 50% FBS with 50% DI water and 100% FBS. As described earlier, these solutions were kept at pH 5 in solution. The response signals in the three environments exhibited similar profiles over the time period. In PBS, the microcantilever was significantly deflected. The response signals were considerably reduced in the presence of a complex serum environment. As expected, the resistance change of 0.04 Ω in 100% serum was even lower than that of 0.08 Ω in 50% serum. The surface stresses were 0.24 N·m−1 in 100% serum, a lower response than that of 0.48 N·m−1 in 50% serum. The presence of a complex environment, as well as relevant protein binding to the free valproic acid drug in serum considerably reduced the interaction between the antibody and the valproic acid.


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)

The measured results of 100 μg·mL−1 valproic acid in PBS, 50% serum and pure serum.
© Copyright Policy
Related In: Results  -  Collection

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

biosensors-05-00037-f005: The measured results of 100 μg·mL−1 valproic acid in PBS, 50% serum and pure serum.
Mentions: Figure 5 shows the signals responses for the detection of 100 µg·mL−1 valproic acid drug in three solutions of PBS, 50% FBS with 50% DI water and 100% FBS. As described earlier, these solutions were kept at pH 5 in solution. The response signals in the three environments exhibited similar profiles over the time period. In PBS, the microcantilever was significantly deflected. The response signals were considerably reduced in the presence of a complex serum environment. As expected, the resistance change of 0.04 Ω in 100% serum was even lower than that of 0.08 Ω in 50% serum. The surface stresses were 0.24 N·m−1 in 100% serum, a lower response than that of 0.48 N·m−1 in 50% serum. The presence of a complex environment, as well as relevant protein binding to the free valproic acid drug in serum considerably reduced the interaction between the antibody and the valproic acid.

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.