Location: Foodborne Toxin Detection and Prevention
Title: Thousand-fold fluorescent signal amplification for mHealth diagnostics Authors
Submitted to: Biosensors and Bioelectronics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 26, 2013
Publication Date: July 17, 2013
Citation: Balsam, J., Rasooly, R., Bruck, H.A., Rasooly, A. 2013. Thousand-fold fluorescent signal amplification for mHealth diagnostics. Biosensors and Bioelectronics. 51:1-7. Interpretive Summary: In recent years, mobile phones and webcam applications have been developed for various biomedical diagnostics applications, however, mobile devices have limited sensitivity for detection. The objective of the present study is to reduce the incidence of food poisoning outbreaks by increasing the detection sensitivity of foodborne pathogens. In the present study, we show that using a simple low cost attachment improves the sensitivity of mobile devices by 1000 fold to the same level as expensive medical laboratory diagnostic equipment.
Technical Abstract: The low sensitivity of Mobile Health (mHealth) optical detectors, such as those found on mobile phones, is a limiting factor for many mHealth clinical applications. To improve sensitivity, we have combined two approaches for optical signal amplification: (1) a computational approach based on an image stacking algorithm to decrease the image noise and enhance weak signals, and (2) an optical signal amplifier utilizing a capillary tube array. These approaches were used in a detection system which includes a multi-wavelength LEDs capable of exciting many fluorophores in multiple wavelengths, a mobile phone or a webcam as a detector, and capillary tube array configured with 36 capillary tubes for signal enhancement. The capillary array enables a ~100X increase in signal sensitivity for fluorescein, reducing the limit of detection (LOD) for mobile phones and webcams from 1000 nM to 10 nM. Computational image stacking enables another ~10X increase in signal sensitivity, further reducing the LOD for webcam from 10 nM to 1 nM. To demonstrate the feasibility of the device for the detection of disease-related biomarkers, Adenovirus DNA labeled with SYBR Green or fluorescein was analyzed by both our capillary array and a commercial plate reader. The LOD for the capillary array was 5ug/mL, and that of the plate reader was 1 ug/mL. Similar results were obtained using DNA stained with fluorescein. The combination of the two signal amplification approaches enables a ~1000X increase in LOD for the webcam platform. This brings it into the range of a conventional plate reader while using a smaller sample volume (10ul) than the plate reader requires (100 ul). This suggests that such a device could be suitable for biosensing applications where up to 10 fold smaller sample sizes are needed. The simple optical configuration for mHealth described in this paper employing the combined capillary and image processing signal amplification is capable of measuring weak fluorescent signals without the need of dedicated laboratories. It has the potential to be used to increase sensitivity of other optically based mHealth technologies, and may increase mHealth’s clinical utility, especially for telemedicine and for resource-poor settings and global health applications. Highlights: The combination of the two signal amplification approaches, (a) the computational image stacking algorithm and (b) the capillary array optical signal amplification, enables a ~1000X increase in fluorescence signal sensitivity that has the potential to improve the sensitivity of many mHealth detectors and their clinical utility for many diagnostics applications.