Sensitivity and limit of detection (LOD) enhancement are essential criteria for the development of ultrasensitive molecular sensors. Although various sensor types have been investigated to enhance sensitivity and LOD, analyte detection and its quantification are still challenging, particularly for protein-protein interactions with low association constants. To solve this problem, here, we used ion concentration polarization (ICP)-based preconcentration to increase the local concentration of analytes in a microfluidic platform for LOD improvement. This was the first demonstration of a microfluidic device with an integrated ICP preconcentrator and interdigitated microelectrode (IME) sensor to detect small changes in surface binding between antigens and antibodies. We detected the amyloid beta (Aβ) protein, an Alzheimer's disease marker, with low binding affinity to its antibodies by adopting ICP preconcentration phenomena. We demonstrated that a combination of ICP preconcentrator and IME sensor increased the LOD by 13.8-fold to femtomolar level (8.15 fM), which corresponds to a significant advance for clinical applications.
Bibliographical noteFunding Information:
Y.K. Yoo and Prof. D.S. Yoon contributed equally to this work. The authors are grateful for financial support from the Korea Health Industry Development Institute (KHIDI, grant no. HI14C3319) and National Research Foundation of Korea (NRF, grant no. NRF-2017M3A9E2058046) and the Korean Government (MEST) (NRF-2015R1D1A1A01059806). We are grateful to Jongyoon Han at MIT, USA for helpful discussion.
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