Ultra-rapid, sensitive and specific digital diagnosis of HIV with a dual-channel SAW biosensor in a pilot clinical study

Abstract

Despite widened access to HIV testing, around half of those infected worldwide are unaware of their HIV-positive status and linkage to care remains a major challenge. Current rapid HIV tests are typically analogue risking incorrect interpretation, no facile electronic data capture, poor linkage to care and data loss for public health. Smartphone-connected diagnostic devices have potential to dramatically improve access to testing and patient retention with electronic data capture and wireless connectivity. We report a pilot clinical study of surface acoustic wave biosensors based on low-cost components found in smartphones to diagnose HIV in 133 patient samples. We engineered a small, portable, laboratory prototype and dual-channel biochips, with in-situ reference control coating and miniaturised configuration, requiring only 6 µL plasma. The dual-channel biochips were functionalized by ink-jet printing with capture coatings to detect either anti-p24 or anti-gp41 antibodies, and a reference control. Biochips were tested with 31 plasma samples from patients with HIV, and 102 healthy volunteers. SH-SAW biosensors showed excellent sensitivity, specificity, low sample volumes and rapid time to result, and were benchmarked to commercial rapid HIV tests. Testing for individual biomarkers found sensitivities of 100% (anti-gp41) and 64.5% (anti-p24) (combined sensitivity of 100%) and 100% specificity, within 5 min. All positive results were recorded within 60 s of sample addition with an electronic readout. Next steps will focus on a smartphone-connected device prototype and user-friendly app interface for larger scale evaluation and field studies, towards our ultimate goal of a new generation of affordable, connected point-of-care HIV tests.

Current Trends on Surface Acoustic Wave Biosensors

“…Reproduced with permission. [ 51 ] Copyright 2018, Springer Nature.…”

Mobile Microfluidics

“…For example, acoustic microfluidic sensors cost as low as $1.50 for each disposable chip and can quantify the number of proteins bound to their surface [25]. These sensors have been successfully integrated into a microfluidic platform for HIV testing [26].…”

“…Faster reaction times are observed when using volumes at the microliter scale, making microfluidics suitable for flash chemistry applications [27,28]. Gray et al [26] demonstrate that they can use acoustic microfluidics to test for HIV within 5 min (the usual time is 24 h). Sista et al [29,30] developed a digital microfluidic platform to screen newborns for lysosomal storage diseases.…”

“…The research in SAW microfluidics is still in its incipient phase, with most of the work focused on fabrication [77,78] and theoretical modeling [79,80]. Notable results are the prototypes for HIV testing [26] and Pseudomonas aeruginosa detection [81]. According to the most recent survey, the trend is towards diagnosis and treatment of infectious diseases [82,83].…”

Evaluation of Shear Horizontal Surface Acoustic Wave Biosensors Using “Layer Parameter” Obtained from Sensor Responses during Immunoreaction

“…On-site diagnostic tests that require field-portable medical devices are categorized under point-of-care testing (POCT). Shear-horizontal surface acoustic wave (SH-SAW) technology-based [1][2][3][4][5][6] biosensors are considered promising candidates for the…”