Abstract
In this work we present a CMOS high frequency direct immunosensor operating at 6 GHz (C-band) for label free determination of creatinine. The sensor is fabricated in standard 0.13 μm SiGe:C BiCMOS process. The report also demonstrates the ability to immobilize creatinine molecules on a Si3N4 passivation layer of the standard BiCMOS/CMOS process, therefore, evading any further need of cumbersome post processing of the fabricated sensor chip. The sensor is based on capacitive detection of the amount of non-creatinine bound antibodies binding to an immobilized creatinine layer on the passivated sensor. The chip bound antibody amount in turn corresponds indirectly to the creatinine concentration used in the incubation phase. The determination of creatinine in the concentration range of 0.88-880 μM is successfully demonstrated in this work. A sensitivity of 35 MHz/10 fold increase in creatinine concentration (during incubation) at the centre frequency of 6 GHz is gained by the immunosensor. The results are compared with a standard optical measurement technique and the dynamic range and sensitivity is of the order of the established optical indication technique. The C-band immunosensor chip comprising an area of 0.3 mm(2) reduces the sensing area considerably, therefore, requiring a sample volume as low as 2 μl. The small analyte sample volume and label free approach also reduce the experimental costs in addition to the low fabrication costs offered by the batch fabrication technique of CMOS/BiCMOS process.
Highlights
Over the last few decades, Enzyme Linked Immunosorbent Assays (ELISAs) have been developed as standard methods in clinical diagnostics
The simulation indicates, for an aqueous solution environment, the capacitance of the interdigitated capacitor (IDC) increases with the increase in concentration of creatinine molecules used for the incubation of the antibodies
With air as the surrounding medium (ε = 1), the Optical measurement of creatinine concentration Optical measurements were performed with Si3N4 test chips to find the best immobilization and test conditions which should be applied for the IDC sensor chips
Summary
Over the last few decades, Enzyme Linked Immunosorbent Assays (ELISAs) have been developed as standard methods in clinical diagnostics. In the rapidly growing area of point-ofcare testing (POCT), lateral flow assays or as they are frequently referred, immunochromatographic assays, are the commonly used methods.[1,2,3,4] since the readout gives only qualitative to semi-quantitative results, the application is limited to diagnose diseases which are accompanied with high changes in analyte concentration. Antibody-based biosensors (immunosensors) are able to measure the analyte quantitatively.[5,6] state of the art immunosensors require several incubation or manual pipetting steps.[7] For easy handling, which is mandatory for POCT, the immunosensor devices should work autonomously. One way is to use an ELISA-like immunosensor format for an autonomous
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