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Biomarker detection and quantification in body fluids is widely utilized in medical diagnosis as it provides useful information for developing treatment strategies. Once attached to target biomarker molecules, fluorescence can be used to detect and quantify the target biomarkers. However, expression of target biomarkers in body fluids is generally weak, and therefore direct utilization of fluorescence for detection with high sensitivity and selectivity is challenging. To address this issue, fluorescence enhancement of target biomarkers has been investigated by several research groups. These studies utilized light-metal-fluorophore interactions and have reported about few thousand-fold fluorescence enhancement. Fluorescence enhancement of few thousand folds enables the detection of molarities up to about nanomolar. However, medical diagnosis, especially early diagnosis, requires detection limit of attomolar. To extend the capabilities of fluorescence enhancement to be applicable in the full range of medical diagnosis, we have used low frequency electric fields (<20 MHz) to further enhance the light-metal-fluorophore interactions. This paper presents the results from our simulation work performed to show how electric fields could modulate the fluorescence enhancement. Moreover, we have found that external electric fields can be used to place the fluorophore molecules outside the quenching regions, align fluorophore dipoles with plasmonic axis of metal and place the fluorophore in the high electric field region of the scattered light. These capabilities could lead to fluorescence enhancement up to about billion-fold that enables attomolar detection. In addition to enhancing the fluorescence, we have also studied the effect of electric fields on localized surface plasmon resonance (LSPR).
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