A portable centrifugal analyser for liver function screening

Abstract

Mortality rates of up to 50% have been reported after liver failure due to drug-induced hepatotoxicity and certain viral infections (Gao et al. 2008). These adverse conditions frequently affect HIV and tuberculosis patients on regular medication in resource-poor settings. Here, we report full integration of sample preparation with read-out of a 5-parameter liver assay panel (LAP) on a portable, easy-to-use, fast and costefficient centrifugal microfluidic analysis system (CMAS). Our unique, dissolvable-film based centrifugopneumatic valving was employed to provide sample-to-answer fashion automation for plasma extraction (from finger-prick of blood), metering and aliquoting into separate reaction chambers for parallelized colorimetric quantification during rotation. The entire LAP completes in less than 20 minutes while using only a tenth the reagent volumes when compared with standard hospital laboratory tests. Accuracy of in-situ liver function screening was validated by 96 separate tests with an average coefficient of variance (CV) of 7.9% compared to benchtop and hospital lab tests. Unpaired two sample statistical t-tests were used to compare the means of CMAS and benchtop reader, on one hand; and CMAS and hospital tests on the other. The results demonstrate no statistical difference between the respective means with 94% and 92% certainty of equivalence, respectively. The portable platform thus saves significant time, labour and costs compared to established technologies, and therefore comply with typical restrictions on lab infrastructure, maintenance, operator skill and costs prevalent in many field clinics of the developing world. It has been successfully deployed in a centralised lab in Nigeria. IntroductionLiver is the largest solid organ in the body and is largely responsible for metabolism and detoxification. (Gao et al. 2008) Liver function tests are widely used in clinical chemistry to assess therapeutic effects and potential medication-induced liver damage, especially when taking medications for HIV, tuberculosis and cancer. (Landis et al. 2013;Rahmioglu et al. 2009; Vella et al. 2012) Literature reports suggest that a mortality rate of 2 -28% can be linked with medication-induced liver damage. (Vella et al. 2012) As a result, monitoring of liver function when on certain medications has become common practice in developed countries but can be expensive in poor resource areas. This has prompted local governments and international funding agencies to set up centralised laboratories for liver function monitoring tests especially for HIV patients. Nonetheless, transport logistics and accessibility remains a significant challenge for the majority of these patients. Thus it is very important to develop portable point-of-care (PoC) devices that could be used for liver function screening in the field. Currently, there are only a handful of sample-to-answer PoC devices available for deployment in the field. Recently, Vella et al.(Vella et al. 2012) demonstrated an innovative micropatterned paper device fo...

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