Abstract
In this paper, we present the development of a photonic biosensor device for cancer treatment monitoring as a complementary diagnostics tool. The proposed device combines multidisciplinary concepts from the photonic, nano-biochemical, micro-fluidic and reader/packaging platforms aiming to overcome limitations related to detection reliability, sensitivity, specificity, compactness and cost issues. The photonic sensor is based on an array of six asymmetric Mach Zender Interferometer (aMZI) waveguides on silicon nitride substrates and the sensing is performed by measuring the phase shift of the output signal, caused by the binding of the analyte on the functionalized aMZI surface. According to the morphological design of the waveguides, an improved sensitivity is achieved in comparison to the current technologies (<5000 nm/RIU). This platform is combined with a novel biofunctionalization methodology that involves material-selective surface chemistries and the high-resolution laser printing of biomaterials resulting in the development of an integrated photonics biosensor device that employs disposable microfluidics cartridges. The device is tested with cancer patient blood serum samples. The detection of periostin (POSTN) and transforming growth factor beta-induced protein (TGFBI), two circulating biomarkers overexpressed by cancer stem cells, is achieved in cancer patient serum with the use of the device.
Highlights
Two out of the six sensing asymmetric Mach Zender Interferometer (aMZI) were biomodified with the anti-transforming growth factor beta-induced protein (TGFBI) antibody, two with the anti-POSTN antibody and the remaining two with polyclonal mouse IgG, which was used as a negative control
The results show a significant amount of specific binding, while the multiplex detection of different analytes is demonstrated as the binding of both TGFBI and POSTN samples to their immobilized antibodies can take place on the same photonic chip
We present the development of a miniaturized, reliable biosensing system for accurate and highly sensitive detection of protein cancer biomarkers, for the treatment monitoring of cancer disease and the therapeutics response
Summary
The vast majority of cancer diagnostics rely on are polymerase chain reaction (PCR), enzyme linked immunosorbent assay (ELISA), radioimmunoassay (RIA), immunohistochemistry (IHC) and flow cytometry [5,6,7], which are based on genomic and proteomic molecular analyses. Even though these techniques are proven efficient, they are performed in hospitals or laboratories that are often located far from the actual site of patient care and need to be equipped with large and complex instruments often requiring highly skilled personnel to operate. A major challenge, in cancer therapeutic monitoring is the development of robust, reliable and even portable diagnostic devices that will allow the detection of cancer biomarkers in locations such as community hospitals, the doctor’s office or perhaps even at home in the future
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