We present a low-cost integrated nanophotonic lab-on-a-chip platform suitable for point-of-care (POC) biomarker analysis.

Tuberculosis (TB) is the leading global cause of death from a single infectious agent. Registered incidence rates are low, especially in low-resource countries with weak health systems, due to the disadvantages of current diagnostic techniques. A major effort is directed to develop a point-of-care (POC) platform to reduce TB deaths with a prompt and reliable low-cost technique. In the frame of the European POCKET Project, a novel POC platform for the direct and non-invasive detection of TB in human urine was developed. The photonic sensor is integrated in a disposable cartridge and is based on a highly sensitive Mach-Zehnder Interferometer (MZI) transducer combined with an on-chip spectral filter. The required elements for the read-out are integrated in an instrument prototype, which allows real-time monitoring and data processing. In this work, the novel POC platform has been employed for the direct detection of lipoarabinomannan (LAM), a lipopolysaccharide found in the mycobacterium cell wall. After the optimization of several parameters, a limit of detection of 475 pg/mL (27.14 pM) was achieved using a direct immunoassay in undiluted human urine in less than 15 minutes. A final validation of the technique was performed using twenty clinical samples from TB patients and healthy donors, allowing the detection of TB in people regardless of HIV coinfection. The results show excellent correlation to those obtained with standard techniques. These promising results demonstrate the high sensitivity, specificity and applicability of our novel POC platform, which could be used during routine checkups in developing countries.

After more than decade of activities in the field of microfluidics, an increasing need for standardized modules and offthe-shelf components can be observed [ 1 , 2 , 3 , 4 ]. In particular the compatibility with existing laboratory equipment o procedures greatly helps the acceptance of miniaturized systems, as in practice, miniaturized systems are very likely to be used in parallel with existing equipment and are not totally replacing this. In this paper we present the basic concept of a microfluidic toolbox with interchangeable components where the external dimensions are adopted from existing standards. Furthermore the fluidic interfaces were selected for compat ibility to established systems.

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Time-of-flight (TOF) magnetic sensing of rolling immunomagnetically-labeled cells offers great potential for single cell function analysis at the bedside in even optically opaque media, such as whole blood. However, due to the spatial resolution of the sensor and the low flow rate regime required to observe the behavior of rolling cells, the concentration range of such a workflow is limited. Potential clinical applications, such as testing of leukocyte function, require a cytometer which can cover a cell concentration range of several orders of magnitude. This is a challenging task for an integrated dilution-free workflow, as for high cell concentrations coincidences need to be avoided, while for low cell concentrations sufficient statistics should be provided in a reasonable time-to-result. Here, we extend the spatial bandwidth of a magnetoresistive sensor with an adaptive and integratable workflow concept combining mechanical and magnetophoretic guiding of magnetically labeled targets for in-situ enrichment over a dynamic concentration range of 3 orders of magnitude. We achieve hybrid integration of the enrichment strategy in a cartridge mold and a giant-magnetoresistance (GMR) sensor in a functionalized Quad Flat No-Lead (QFN) package, which allows for miniaturization of the Si footprint for potential low-cost bedside testing. The enrichment results demonstrate that TOF magnetic flow cytometry with adaptive particle focusing can match the clinical requirements for a point-of-care (POC) cytometer and can potentially be of interest for other sheath-less methodologies requiring workflow integration.