HIV Detection via a Carbon Nanotube RNA Sensor

Abstract

Viral illnesses remain a significant concern in global health. Rapid and quantitative early detection of viral oligonucleotides without the need for purification, amplification, or labeling would be valuable in guiding successful treatment strategies. Single-walled carbon nanotube-based sensors recently demonstrated optical detection of small, free oligonucleotides in biofluids and in vivo, although proteins diminished sensitivity. Here, we discovered an unexpected phenomenon wherein the carbon nanotube optical response to nucleic acids can be enhanced by denatured proteins. Mechanistic studies found that hydrophobic patches of the denatured protein chain interact with the freed nanotube surface after hybridization, resulting in enhanced shifting of the nanotube emission. We employed this mechanism to detect an intact HIV in serum, resulting in specific responses within minutes. This work portends a route toward point-of-care optical detection of viruses or other nucleic acid-based analytes.

Review—Chemical and Biological Sensors for Viral Detection

“…According to World Health Organization recent data, 36.9 million people have been affected by HIV worldwide. 90 According to recent studies, it is possible to decrease the transmission up to 96% by early antiretroviral treatment so rapid and accurate point-of-care (POC) detection of HIV infection status is critical for protecting patients. 91 For FET fabrication, graphene was exfoliated on SiO 2 /Si substrate and then electron beam lithography and thermal evaporation techniques were applied to pattern the electrodes.…”

Fluorescent Single-Walled Carbon Nanotubes for Protein Detection

“…This nanosensor was immobilized on a glass surface, on which human blood platelets were cultured, and were shown to detect serotonin release patterns from the cells in real time [115]. Additionally, DNA-wrapped SWCNTs were utilized for the detection of a single-stranded RNA genome of an intact HIV particle [116] and of doxorubicin, a chemotherapy drug effective against dividing cells due to its affinity to DNA [117]. Further, DNA-SWCNTs were engineered to quantify microRNA hybridization, by a solvatochromic-like response following DNA displacement from the nanotubes' surface [118].…”

Derivatized Carbon Nanotubes for Gene Therapy in Mammalian and Plant Cells

“…HIV infected cells develop multiple strains upon mutation and hence developing a siRNA delivery system that can target multiple genes is an area worth exploring. Harvey et al [75] took advantage of fluorescence to develop single-walled carbon nanotube based sensor for the detection of HIV in the serum. Mechanistic studies have shown that the hydrophobic residues from the denatured protein lead to an enhancement in the blue shift when bound to the newly exposed nanotube surface.…”

“…HIV infected cells develop multiple strains upon mutation and hence developing a siRNA delivery system that can target multiple genes is an area worth exploring. Harvey et al . took advantage of fluorescence to develop single‐walled carbon nanotube based sensor for the detection of HIV in the serum.…”