Paper and Flexible Substrates as Materials for Biosensing Platforms to Detect Multiple Biotargets

Abstract

The need for sensitive, robust, portable, and inexpensive biosensing platforms is of significant interest in clinical applications for disease diagnosis and treatment monitoring at the point-of-care (POC) settings. Rapid, accurate POC diagnostic assays play a crucial role in developing countries, where there are limited laboratory infrastructure, trained personnel, and financial support. However, current diagnostic assays commonly require long assay time, sophisticated infrastructure and expensive reagents that are not compatible with resource-constrained settings. Although paper and flexible material-based platform technologies provide alternative approaches to develop POC diagnostic assays for broad applications in medicine, they have technical challenges integrating to different detection modalities. Here, we address the limited capability of current paper and flexible material-based platforms by integrating cellulose paper and flexible polyester films as diagnostic biosensing materials with various detection modalities through the development and validation of new widely applicable electrical and optical sensing mechanisms using antibodies and peptides. By incorporating these different detection modalities, we present selective and accurate capture and detection of multiple biotargets including viruses (Human Immunodeficieny Virus-1), bacteria (Escherichia coli and Staphylococcus aureus), and cells (CD4+ T lymphocytes) from fingerprick volume equivalent of multiple biological specimens such as whole blood, plasma, and peritoneal dialysis effluent with clinically relevant detection and sensitivity.

Qualitative and quantitative detection of T7 bacteriophages using paper based sandwich ELISA

“…Paper has the potential to meet these criteria. Researchers demonstrated that antibody and enzyme active papers can detect ABO blood typing [1], bacteria [11], DNA [12], alcohol content in the breath [13], seafood freshness [14], and pathogens in biofluids [15][16][17][18][19][20]. However, simplicity, sensitivity, and amount of biofluid volume required for the test are ongoing challenges for developing paper based devices to detect pathogens, such as viruses [17][18][19][20][21].…”

Advances in Nanotechnology and Microfluidics for Human Papillomavirus Diagnostics

“…Further, diagnosis and differentiation of HPV genotypes at the early stage would allow early treatment, thus decreasing severity of infection and mortality. Recent advances in microfluidics and labchip systems including optical [48]- [50], electrical [84], mechanical [85], and microchip platforms [86]- [88] allow intact pathogens including bacteria and viruses to be captured, thus enabling invaluable opportunities for postgenomic and proteomic analysis.…”

Multitarget, quantitative nanoplasmonic electrical field-enhanced resonating device (NE 2 RD) for diagnostics

“…Since diseases have complex structures and networks that are affected by many biofunctional units, including various biomarkers, the ability to detect multiple biotargets has great utility in developing clinically useful diagnostic approaches for medical practice. Recently, nanoparticle-based detection strategies have been used to develop biosensing technologies by using their plasmonic features (26) and their aggregation strategies for biotarget detection (40). Although a well-plate-based nanoplasmonic platform was used to detect HIV (41), here we show, for the first time to our knowledge, that the NE 2 RD provides (i) an unprecedented multitarget capability whereby we detect multiple biotargets (i.e., protein biomarkers, drugs, protein allergens, bacteria, eukaryotic cells, and distinct viruses); (ii) versatility in detecting targets from distinct clinical matrices such as saliva, serum, and whole blood; and (iii) portability potentially allowing applications at the POC.…”