Convergence of Quantum Dot Barcodes with Microfluidics and Signal Processing for Multiplexed High-Throughput Infectious Disease Diagnostics

Abstract

Through the convergence of nano- and microtechnologies (quantum dots and microfluidics), we have created a diagnostic system capable of multiplexed, high-throughput analysis of infectious agents in human serum samples. We demonstrate, as a proof-of-concept, the ability to detect serum biomarkers of the most globally prevalent blood-borne infectious diseases (i.e., hepatitis B, hepatitis C, and HIV) with low sample volume (<100 microL), rapidity (<1 h), and 50 times greater sensitivity than that of currently available FDA-approved methods. We further show precision for detecting multiple biomarkers simultaneously in serum with minimal cross-reactivity. This device could be further developed into a portable handheld point-of-care diagnostic system, which would represent a major advance in detecting, monitoring, treating, and preventing infectious disease spread in the developed and developing worlds.

Application of nanodiagnostics in point-of-care tests for infectious diseases

“…A successful integrated nanodevice with high-throughput and multiplexed detecting ability for the most important blood-borne infecting agents such as HIV, HBV, and HCV in serum samples has been developed through the combination of nanotechnology (quantum dots) and microtechnology (microfluidics) (Figure 2). 62 Through this diagnosis, multiple pathogens could be detected precisely using the human serum samples simultaneously. The detection limitation of this diagnosis for the requiring serum volumes could be as low as 100 µL, and the detection could be finished within 1 hour, and the sensitivity is more than 50 times of the US Food and Drug Administration currently approved platforms.…”

“…The detection limitation of this diagnosis for the requiring serum volumes could be as low as 100 µL, and the detection could be finished within 1 hour, and the sensitivity is more than 50 times of the US Food and Drug Administration currently approved platforms. 62 Another successfully developed nanodiagnostic platform for HIV was based on the detection of viral envelope glycoprotein gp120 using a mesoporous silica-based nanodevice. 63 The nanosystems were coated with the human host cell surface receptor CD4 or an 18-mer peptide that mimics the gp120 binding region.…”

Evidence-based consensus on the diagnosis, prevention and management of hepatitis C virus disease

“…Moreover, gold nanoparticles varying from 2 to 50 nmol/L in size have been used to detect HCV RNA and antiHCV [28] . Antibodies to HIV, HBV, HCV, have been detected through a multiplex platform that uses a microfluidic chip and quantum dots coated with antigen are embedded in beads made of polystyrene having a sensitivity of pM concentration [29,30] . Another important method working on the principle of amplification, named loopmediated isothermal amplification (LAMP) has been used for detection of HCV RNA [31,32] .…”

Application of semiconductor and metal nanostructures in biology and medicine

“…Examples include quantitative in vitro immunoassays 5,[36][37][38][39] and the labeling of fixed cell samples 40,41 and tissue specimens. 42 Labeling of the membrane receptors of live cells at the single-molecule level has also been achieved.…”

“…Due to these properties, the incorporation of nanostructures in detection schemes or the use the nanostructures as contrast agents could improve the specificity and accuracy of current diagnostics. [5][6][7][8][9] Furthermore, nanostructures can improve the effectiveness of drugs in the treatment of a variety of diseases when they are used as delivery vehicles because of the increase in therapeutic payload. [10][11][12] In the last fifteen years, researchers have characterized the tunable properties by altering the nanostructure size, shape, and chemical composition and have developed reproducible strategies to make nanostructures of desired properties.…”