# A fully automated, ultrasensitive luminescence cascade sensor to address hepatitis C diagnostic disparity

## TL;DR

A new automated, highly sensitive test for hepatitis C was developed to improve early diagnosis in underserved populations.

## Contribution

A fully automated, ultrasensitive point-of-care HCV antigen test using bioluminescence cascade amplification is introduced.

## Key findings

- The test achieved 97% sensitivity, 94% specificity, and 96% accuracy in 71 AI/AN samples.
- The assay provides results within 30 minutes, enabling rapid and accessible HCV screening.
- This technology addresses diagnostic disparities in resource-limited and vulnerable populations.

## Abstract

Viral hepatitis poses a significant global health burden, with chronic hepatitis B and C causing about 1 million annual deaths from liver cancer and cirrhosis. Over 1.5 million new hepatitis C virus (HCV) cases arise yearly, especially among vulnerable groups like American Indians and Alaska Natives (AI/AN). Despite effective direct-acting antivirals, early HCV diagnosis remains challenging, particularly in resource-limited settings. Current two-step testing methods are costly and prone to patient dropout. Point-of-care (POC) HCV antigen (Ag) testing offers a promising early detection approach, but no US Food and Drug Administration (FDA)-approved POC test meets the sensitivity and specificity needed for low viral loads. To address this, we developed a fully automated bioluminescence-based POC assay using a cascade-based signal amplification strategy. Evaluated on 71 AI/AN samples, it showed 97% sensitivity, 94% specificity, and 96% accuracy. This technology can improve health equity by enabling accessible and reliable HCV testing for disproportionately affected populations.

•HCV infects 1.5 million people yearly, with American Indians and Alaska Natives most affected.•Current two-step diagnostics are costly and slow and lead to high dropout rates among patients.•Developed a sensitive, user-friendly, automated point-of-care antigen test based on bioluminescence imaging.•In 71 AI/AN samples, the assay showed 97% sensitivity, 94% specificity, and 96% accuracy within 30 min.•This technology enables early intervention and expands HCV screening in resource-limited settings.

HCV infects 1.5 million people yearly, with American Indians and Alaska Natives most affected.

Current two-step diagnostics are costly and slow and lead to high dropout rates among patients.

Developed a sensitive, user-friendly, automated point-of-care antigen test based on bioluminescence imaging.

In 71 AI/AN samples, the assay showed 97% sensitivity, 94% specificity, and 96% accuracy within 30 min.

This technology enables early intervention and expands HCV screening in resource-limited settings.