KEYWORDS: Lab on a chip, Organic semiconductors, System integration, Microfluidics, Control systems, Liquids, Diagnostics, Life sciences, Luminescence, Fluorescence spectroscopy
While lab-on-a-chip systems have become more and more widely used in many fields in diagnostics, analytical and life sciences, most of the systems still have to be considered as stationary, typically desktop-sized instruments. While the actual microfluidic cartridge often is comparatively compact, the associated instrument to operate this cartridge remains large, limiting the use of such systems in applications outside of a laboratory environment. Two main aspects contribute to this situation: Detection systems, especially sensitive optical (e.g. fluorescence) detection systems remain relatively large. The fluidic control elements, especially when reagents have to be delivered from a reservoir in the instrument to the cartridge, also contribute to the system size and weight. We have tried to circumvent these problems by integrating both the detection system as well as all required liquid reagents into the disposable microfluidic cartridge. The technology used for the realization of the detection system is the multilayer inkjet-printing of organic semiconductor materials (PEDOT:PSS) in order to create light sources and photodetector elements directly on the cartridge. This printing technology can be seamlessly integrated into the manufacturing workflow of the cartridge fabrication. All liquid reagents (currently 6) for an exemplary immunoassay on this platform are integrated using blisters which can be easily actuated either manually or by a simple linear actuator. Data readout as well as system control are planned to be executed using a smartphone, thereby further reducing the complexity and size of the instrument.
In the spring of 2014, the Ebola virus (EBOV) strain Zaire caused a dramatic outbreak in several regions of West Africa. The RT-PCR and antigen capture diagnostic proved to be effective for detecting EBOV in blood and serum. In this paper, we present data of a rapid antigen capture test for the detection of VP40. The test was performed in a microfluidic chip for immunofiltration analysis. The chip integrates all necessary assay components. The analytical sensitivity of the rapid test was 8 ng/ml for recombinant VP40. In serum and whole blood samples spiked with virus culture material, the detection limit was 2.2 x 102 PFU/ml. The performance data of the rapid test (15 min) are comparable to that of the VP40 laboratory ELISA.
KEYWORDS: Microfluidics, Pathogens, Fluorescence spectroscopy, Lab on a chip, Interfaces, Control systems, Liquids, Contamination, Point-of-care devices, Imaging systems
The ability to integrate complete assays on a microfluidic chip helps to greatly simplify instrument requirements and allows the use of lab-on-a-chip technology in the field. A core application for such field-portable systems is the detection of pathogens in a CBRN scenario such as permanent monitoring of airborne pathogens, e.g. in subway stations or hospitals etc. An immunological assay was chosen as method for the pathogen identification. The conceptual approach was its realization as a lab-on-a-chip system, enabling an easy handling of the sample in an automated manner. The immunological detection takes place on an antibody array directly implemented in the microfluidic network. Different immobilization strategies will be presented showing the performance of the system. Central elements of the disposable microfluidic device like fluidic interface, turning valves, liquid introduction and waste storage, as well as the architecture of measurement and control fluidic network, will be introduced. Overall process times of about 30 minutes were achieved and assays for the detection of Francisella tularensis and Yersinia pestis are presented. An important feature of the integrated lab-on-a-chip approach is that all waste liquids remain on-chip and contamination risks can be avoided.
Point-of-care diagnostics (POC) is one of the key application fields for lab-on-a-chip devices. While in recent years much of the work has concentrated on integrating complex molecular diagnostic assays onto a microfluidic device, there is a need to also put comparatively simple immunoassay-type protocols on a microfluidic platform. In this paper, we present the development of a microfluidic cartridge using an immunofiltration approach. In this method, the sandwich immunoassay takes place in a porous frit on which the antibodies have immobilized. The device is designed to be able to handle three samples in parallel and up to four analytical targets per sample. In order to meet the critical cost targets for the diagnostic market, the microfluidic chip has been designed and manufactured using high-volume manufacturing technologies in mind. Validation experiments show comparable sensitivities in comparison with conventional immunofiltration kits.
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