Paper/Polymer Hybrid Microfluidic Biochips for Infectious Disease Diagnosis

Infectious diseases frequently cause public health concerns and they often occur in high-poverty regions. Hence, a simple and low-cost method is in great need for immediate and early diagnosis of infectious diseases. Recently, microfluidic lab-on-a-chip offers a unique opportunity for various biomedical applications. Since different chip substrates have different advantages and limitations, hybrid devices can draw more benefits from different substrates. Therefore, we have developed three paper/polymer hybrid microfluidic biochips integrated with loop-mediated isothermal amplification (LAMP) for high-sensitivity infectious disease diagnosis. We for the first time developed a low-cost paper/polydimethylsiloxane (PDMS) hybrid microfluidic biochip for rapid, sensitive and instrument-free detection of a main meningitis-causing bacterium, N. meningitidis. The hybrid microfluidic biochip with paper inside enabled stable testing results over a much longer period of time than a paper-free microfluidic biochip. Although no any specialized instruments were used, the limit of detection of 3 copies per LAMP zone for N. meningitidis was readily achieved, which was comparable to costly qPCR. We further demonstrated the broader application of our microfluidic approach with high sensitivity and specificity by testing the whooping cough-causing bacterium, B. pertussis, in 100 human clinical samples. On the basis of singleplexed pathogen detection, we developed another paper/PDMS hybrid microfluidic biochip for simultaneous detection of three pathogens, N. meningitidis, S. pneumoniae and Hib, which cause most of the bacterial meningitis. At last, we developed a paper/poly(methyl methacrylate) (PMMA) hybrid CD-like microfluidic SpinChip that integrated with graphene oxide (GO) functionalized nanosensors for the quantitative multiplex LAMP (mLAMP) detection of infectious diseases. Paper in this hybrid system facilitated the simple integration of nanosensors on the SpinChip. These low-cost paper/polymer hybrid microfluidic biochips have great potential for point-of-care (POC) infectious diseases diagnosis, especially in low-resource settings such as physicianâ??s office and developing nations