Sensors and Actuators B 139 (2009) 245–251 Contents lists available at ScienceDirect Sensors and Actuators B: Chemical journal homepage: www.elsevier.com/locate/snb Biochip readout system for point-of-care applications Albrecht Brandenburg a,∗ , Franziska Curdt a , Gerd Sulz a , Frank Ebling b , Jörg Nestler c , Kai Wunderlich d , Dirk Michel d a Fraunhofer Institute of Physical Measurement Techniques, Heidenhofstraße 8, 79110 Freiburg, Germany b Fraunhofer Institute for Reliability and Microintegration IZM, Gustav-Meyer-Allee 25, 13355 Berlin, Germany c Fraunhofer Research Institution for Electronic Nano Systems ENAS, Reichenhainer Str. 88, 09126 Chemnitz, Germany d Fraunhofer Institute for Biomedical Engineering IBMT, Am Mühlenberg 13, 14476 Potsdam-Golm, Germany article info Article history: Available online 9 March 2009 Keywords: Point-of-care Optical sensor Fluorescence immunoassay TIRF C-reactive protein Prostate specific antigen abstract A new low cost biochip readout system based on total internal reflection fluorescence (TIRF) including microfluidics is presented. The system is suitable for point-of-care diagnostics employing disposable substrates made of polymer foils producible at very low costs. Results for the reader sensitivity and dynamic range in comparison to state of the art readers are presented. The sensitivity is comparable to laser scanner systems developed for lab applications, although the newly developed TIRF system is built up much simpler and low cost substrates are used. The dynamic range and the on chip homogeneity were investigated. As an example for future POC applications, an immunoassay for the inflammation parameter C-reactive protein (CRP) is investigated. The sensitivity of these assays is in the range of 1ng/ml, being sufficient for many parameters of clinical relevance. © 2009 Published by Elsevier B.V. 1. Introduction For future point-of-care applications, simple, cheap and easy to handle devices are required, which are able to detect many param- eters very reliably in parallel. With those devices fast diagnostic results may be yielded even for complex diagnostic situations such as for patients being septic or having a cardiac infarction, where fast diagnosis is needed, but also for cancer or other chronic or acute diseases. For many years, several approaches have been reported to detect specific reactions for diagnostic purposes including fluo- rescence methods, label free detection principles and microarrays [1–7]. The readout of fluorescence biochips on the basis of total inter- nal reflection fluorescence (TIRF) is well known for a long time [8–12]. This principle allows the biochip readout with high sensi- tivity in combination with a miniaturised flow cell. Typically, glass slides with polished end faces for the input coupling of light are used as optical elements and carrier for the immobilised receptor molecules. The goal of the present work is the investigation of very low cost TIRF elements fabricated by hot embossing or injection mould- ing. These elements have to be integrated into a polymer cartridge, ∗ Corresponding author. E-mail address: albrecht.brandenburg@ipm.fraunhofer.de (A. Brandenburg). which contains microfluidic elements for transport and mixing of sample and reagents. Reagent containers and actuators may be integrated into this cartridge as well. The readout device shall be designed as an integrated system covering the control of pumps and valves, the readout and the data evaluation. A very simple handling of the overall system is required for use in point-of-care applica- tions. The instrument has to be produced very cost efficiently as well. As an example assay for testing the instrument, the detection of C-reactive protein (CRP) was investigated. CRP is an indicator for inflammation; the physiological concentration is about 5 g/ml. In case of inflammation, a large increase of several orders of magni- tude is observed. This parameter is often investigated in the filed of point-of-care testing together with other parameters. 2. State of the art Diagnostic devices for point-of-care are, e.g. test stripes, which typically detect one parameter per stripe. In the recent years, electrochemical and fluorescence sensors became available, which integrate a few parameters in one cartridge. These tests are com- patible with requirements in diagnostics, but with the technologies used, the potential for multi-parameter analysis is limited. On the other hand, biochip technology is available for lab applications. With this technique, an extremely large number of analytes can be evaluated as up to two million dots can be read out 0925-4005/$ – see front matter © 2009 Published by Elsevier B.V. doi:10.1016/j.snb.2009.02.052