< Back to previous page

Project

SIMPLE point-of-care test for detection of tuberculosis in Africa

The increasing life expectancy in high-income countries, exponential population growth in developing countries, and the impact of climate change effects are several worldwide phenomena, which are expected to drastically increase the incidence of infectious (e.g., tuberculosis, malaria and COVID-19) and chronic diseases (e.g., cardiovascular diseases, cancer and diabetes) on a global scale. In this regard, high-quality diagnostic tests play a crucial role to identify these diseases in an early stage and providing patients with valuable information for proper disease management. In most healthcare systems, however, diagnostic tests are mainly restricted to costly, well-equipped centralized laboratories, which are operated by highly trained personnel. Consequently, a large part of the world population does not have access to them due to limited financial resources, lack of proper infrastructure and logistics, or living in hard-to-reach regions. To make reliable diagnostic tests accessible to everyone everywhere (e.g., at home), healthcare systems must shift towards decentralized and patient-centric approaches. Hereto, remote microsampling techniques and point-of-care testing are two strategies with huge potential by simplifying the sample collection process (self-sampling) or providing immediate on-the-spot diagnostic results in the proximity of the patient.

Lab-on-a-chip (LOC) technologies have promised for years to decouple diagnostic tests from their laboratory environment by integrating and automating complex analytical techniques (i.e., sample preparation and read-out) on miniaturized microfluidic chips. However, the field has mainly been focusing on showing its potential in terms of functionality instead of developing integrated systems that solve real-life problems of the end-user. Consequently, most of the presented LOC devices are still restricted to laboratory settings due to the requirement of ancillary equipment (i.e., syringe pumps) and skilled personnel for operation.

In this context, our research group has developed the (infusion) self-powered microfluidic pump by liquid encapsulation ((i)SIMPLE) technology, which combines paper- and channel-based microfluidics to manipulate small liquid volumes without the need of any active external equipment. The global aim of this PhD thesis was to further expand its microfluidic toolbox towards a modular and programmable LOC platform for decentralized point-of-care applications. The thesis was divided into two research lines, each focusing on a different strategy to achieve decentralized healthcare.

In the first part, a user-friendly microfluidic microsampling device was developed for the autonomous collection and preparation of multiple high-quality dried blood spots (DBS). Hereto, a novel metering concept, exploiting the coordinated burst action of hydrophobic burst valves, was developed, and integrated on the (i)SIMPLE platform to isolate precisely metered volumes from an unknown applied sample source. To make the device compatible with field usage, a user-friendly and robust chip-to-world interface was integrated that, when combined with the proposed pump splitting mechanism, enabled the preparation of multiple DBS samples. This device was validated regarding therapeutic drug monitoring of biopharmaceuticals and shown to be compatible with capillary blood.

In the second part of the thesis, various microfluidic modules were developed enabling on-chip sample pre-processing (i.e., sample metering and dilution), heating and target detection without the need for any external equipment. Stepwise serial dilution was achieved by coupling the developed metering system to a plug merging unit, which was proven to generate accurate and reproducible dilutions up to a 1000-fold dilution factor. Next, the use of phase change materials was exploited to realize controlled localized on-chip heating without the need for any active power supply. Finally, a standalone microfluidic chip capable to perform and automate all liquid handling steps of a lateral flow assay for malaria detection was presented. By coupling all these different modules on the (i)SIMPLE platform, complex multistep bioassays can be integrated and automated without the need for any ancillary equipment. Therefore, we believe that this technology has tremendous potential for the next generation of fully autonomous sample-to-result point-of-care tests.

Date:16 Aug 2017 →  4 Mar 2022
Keywords:Microfluidics, Point-of-care diagnostics, Decentralized healthcare, Microsampling, Self-powered
Disciplines:Microfluidics/flow chemistry, Medical biotechnology diagnostics, Clinical chemistry
Project type:PhD project