Hybrid Paper–Plastic Microchip for Flexible and High‐Performance Point‐of‐Care Diagnostics

Abstract

A low-cost and easy-to-fabricate microchip remains a key challenge for the development of true point-of-care (POC) diagnostics. Cellulose paper and plastic are thin, light, flexible, and abundant raw materials, which make them excellent substrates for mass production of POC devices. Herein, a hybrid paper–plastic microchip (PPMC) is developed, which can be used for both single and multiplexed detection of different targets, providing flexibility in the design and fabrication of the microchip. The developed PPMC with printed electronics is evaluated for sensitive and reliable detection of a broad range of targets, such as liver and colon cancer protein biomarkers, intact Zika virus, and human papillomavirus nucleic acid amplicons. The presented approach allows a highly specific detection of the tested targets with detection limits as low as 102 ng mL−1 for protein biomarkers, 103 particle per milliliter for virus particles, and 102 copies per microliter for a target nucleic acid. This approach can potentially be considered for the development of inexpensive and stable POC microchip diagnostics and is suitable for the detection of a wide range of microbial infections and cancer biomarkers.

Point-of-care diagnostics for infectious diseases: From methods to devices

“…Since firstly introduced by Whitesides et al in 2007, μ PADs have enjoyed booming development for POC diagnostic applications due to their inherent advantages provided by the paper-based substrates, such as hydrophilic and porous structure for microfluidic channels fabrication, low cost, fold ability, disposability, favorable biocompatibility, no need of external driven force for sample transportation, and equipment independence [380] , [381] , [382] , [383] , [384] , [385] , [386] . Typical μ PADs were composed of an arrangement of hydrophilic/hydrophobic microstructures patterned on paper substrates that integrated reagent storage, sample transportation, sorting, mixing, flow control and multiplex detection, making them ideal alternatives for automated field testing and POC diagnostic applications [385] , [386] , [387] .…”

Advances in Diagnostic Methods for Zika Virus Infection

“…Therefore, paperbased devices provide attractive alternative to traditional labbased assays and allows affordable and rapid disease testing [70]. Recently, paper-based microfluidic devices are being investigated for ZIKV detection [73,74]. At one instance, paper-based device consists of a large area at the top for sample loading (blood or plasma) followed by several areas coated with specific antibodies against ZIKV's NS1 protein [73].…”

“…Microfluidic devices provide a precise control on fluid flow and are widely investigated for various applications including disease detection [87][88][89][90][91], sample analysis [88], and biosensing [92][93][94][95]. The previous studies have shown that microfluidic devices can be used for the quantification of various viruses [69,74] and proteins through impedance sensing [96,97]. Recently, newly designed biochips integrating with electrical detection electrodes have been optimized by the addition of pillar structures, which serve to facilitate the functionalization of probes inside the chip, thus increasing the hit rate of target proteins [98].…”

“…Recently, impedance sensing has also been utilized to detect various viruses including HIV and ZIKV viruses [69,74]. In this method, whole viruses are captured using magnetic beads functionalized with specific antibodies.…”

“…The virus lysis step releases ions and biomolecules, which change the impedance of the sample. This impedance change is rapidly detected using paper-based flexible microfluidic devices viruses [69,74]. These impedance-based sensing methods provide rapid detection of disease (<30 min); however, quantification of viruses especially at low concentration is challenging and requires further investigation.…”