(88f) Point-of-Care Cancer Biomarker Detection System Integrating Surface Acoustic Wave Streaming and Metal-Enhanced Fluorescence

Point-of-care cancer biomarker detection system integrating surface acoustic wave streaming and metal-enhanced fluorescence

Yuqi Huang, Shuangming Li and Venkat R. Bhethanabotla

yuqi@usf.edu

shuangming@mail.usf.edu

bhethana@usf.edu

Department of Chemical and Biomedical Engineering, University of South Florida, Tampa, Florida 33620-5350, USA

Abstract:

Immunofluorescence is one of the primary techniques for microbiological assays. It can help to visualize, identify, and even quantify the interaction between antibody and antigen, some even used for DNA and protein detection.^1,2 However, there is a clinical need of increasing its limit of detection, specificity and portability. In this work, a portable optical fluorescence system was designed to be combined with a direct digital synthesizer for surface acoustic wave (SAW) generation and metal-enhanced fluorescence (MEF) to lower the detection limit in immunofluorescence assays.^3,4 MEF was achieved by depositing silver nanoparticles with covered silica film, which can plasmonically enhance fluorescence intensity. Rayleigh wave streaming was generated on a piezoelectric device for surface acoustic wave streaming purpose, which can prevent nonspecific binding on the biological interface.⁵ The miniaturized prototype, integrating acoustic wave removal of interfering proteins combined with optical detection, was developed to realize immune detection on a portable platform with limit of detection at nanogram per milliliter level in detecting carcinoembryonic antigen (CEA) from human plasma.

Recent work shows that the MEF substrate fabricated with the above method can lower the detection limit of CEA from PBS to 100pg/mL level. However, testing the detection limit for CEA from human plasma has raised to 500ng/mL. Non-specific proteins, dusts and electrolytes in human plasma are primary suspects to raise background noise which increases the limit of detection. Further tests show that by adding SAW streaming to the sample tested on MEF substrate, the detection limit brings back down to 50pg/mL. A reasonable inference to this detection limit drop is the removal of non-specific protein by streaming surface acoustic wave to the sample surface, where the non-specific absorbents are removed by shear force from the wave, and the background noise is reduced to lower the limit of detection for CEA from human plasma.

1. K. Aslan, I. Gryczynski, J. Malicka, E. Matveeva, J. R. Lakowicz, and C. D. Geddes, "Metal-enhanced fluorescence: an emerging tool in biotechnology," Current Opinion in Biotechnology, vol. 16, pp. 55-62, 2005.
2. R. A. Goldsby, T. J. Kindt, B. A. Osborne, and J. Kuby, "Immunology," ed: New York: WH Freeman, 2003.
3. S. Li and V. Bhethanabotla, “Design of a Portable Orthogonal Surface Acoustic Wave Sensor System for Simultaneous Sensing, Removal of Nonspecifically bound Proteins and Mixing”, Sensors, vol. 19(18), 2019.
4. Liu, J.; Li, S.; Bhethanabotla, V. R., Integrating Metal-Enhanced Fluorescence and Surface Acoustic Waves for Sensitive and Rapid Quantification of Cancer Biomarkers from Real Matrices. ACS Sensors, 3 (1), 222-229, 2018.
5. S. Cular, D. W. Branch, V. R. Bhethanabotla, G. D. Meyer, and H. G. Craighead, "Removal of nonspecifically bound proteins on microarrays using surface acoustic waves," IEEE Sensors journal, vol. 8, pp. 314-320, 2008.