AixSense 2019
Contents
AixSense 2019
AixSense is a team from the RWTH Aachen University competing in the SensUs 2019 event. For SensUs 2019, AixSense investigated the possibilities for creating a biosensor which is able to measure the concentration of Adalimumab. The full TRD can be found [ via this link]
Method
Electro-Impedance Spectroscopy (EIS). Anti-Adalimumab (Anti-AM) is used to immobilize the surface of the graphene based transducers where the analyte then flows over. Changes in the impedance before and after the flow are measured using an Impedance Analyzer. Adalimumab specific transducers will then show increase of impedance against different concentrations of Adalimumab molecular binding within clinical ranges (0.1μg/ml to 10 μg/ml).
Molecular Recognition
The molecules used in the biosensor are the Anti-Adalimumab Type 1 Antibody, the TNF-α - Tumour Necrosis Factor alpha (TNF-α), and silver Nanoparticles.
The Type 1 anti-adalimumab (Anti-AM) antibodies inhibit the binding of the drug adalimumab(AM) to its target, TNF-α, and therefore detect the free drug. This protein was used to bio-immobilize the Graphene based transducers.
The tumour Necrosis Factor alpha (TNF-α), is an inflammatory cytokine produced by macrophages/monocytes during acute inflammation and is responsible for a diverse range of signalling events within cells, leading to necrosis or apoptosis.The affinity of TNF-α to adalimumab was taken advantage of by tagging it with optically active silver nanoparticles and then flowing it over the Graphene based transducers containing the Anti-AM complex.
The Silver Nanoparticles (Ag NPs) were used as the optical tags with receptor proteins specific to AM.
Physical Transduction
The graphene based transducers allows for electrical readouts for the specific binding of AM and the optical readout for the recording of optical emissions from the labelled secondary antibodies of TNF- alpha which specifically binds to the Anti-AM AM complex bio that are immobilized on the Graphene transducers. Moreover, dedicated microfluidic circuits increasing the local concentrations of the analytes at the transducer enhance the optical signal and improve the bioassay readout.
An optical based detection has also been installed as a parallel detection platform for increased accuracy of the results.
For the optical detection, Microscale Thermophoresis (MST) is utilised.
Directed movement of particles in a microscopic temperature gradient leads to accumulation of analyte molecules and thus leads to an enhanced sensor signal due to the increased local fluorescence.
Cartridge
For measuring the concentration of AM, blood samples containing the drug are injected into the disposable chips (having graphene electrodes functionalized with Anti-AM) and then the optically labelled TNFα is made to flow through it. Once the fluid is stationary, the electrical and optical measurements are made in the respective platforms and the chips are disposed after each measurement.
Reader Instrument
The entire setup is 20x20x40 cm^3 in dimensions.
The user administers the blood sample and TNFα in the chip and put the chip in the measurement system. The electrical readout is then measured using an Impedance Analyzer, where the impedance change obtained at a particular frequency will indicate the concentrations. The optical readout is an image of the fluorescence captured by the camera.
Furthermore, there is an integrated optoelectronic read out platform in order to improve the accuracy and speed of measurement.
