A Miniature Bio-Photonics Companion Diagnostics Platform for Reliable Cancer Treatment Monitoring in Blood Fluids.

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.

Versatile (bio)functionalization of bromo-terminated phosphonate-modified porous aluminum oxide.

Porous aluminum oxide (PAO) is a nanoporous material used for various (bio)technological applications, and tailoring its surface properties via covalent modification is a way to expand and refine its application. Specific and complex chemical modification of the PAO surface requires a stepwise approach in which a secondary reaction on a stable initial modification is necessary to achieve the desired terminal molecular architecture and reactivity. We here show that the straightforward initial modification of the bare PAO surface with bromo-terminated phosphonic acid allows for the subsequent preparation of PAO with a wide scope of terminal reactive groups, making it suitable for (bio)functionalization. Starting from the initial bromo-terminated PAO, we prepared PAO surfaces presenting various terminal functional groups, such as azide, alkyne, alkene, thiol, isothiocyanate, and N-hydroxysuccinimide (NHS). We also show that this wide scope of easily accessible tailored reactive PAO surfaces can be used for subsequent modification with (bio)molecules, including carbohydrate derivatives and fluorescently labeled proteins.

Micro- and nanopatterning of functional organic monolayers on oxide-free silicon by laser-induced photothermal desorption.

The photothermal laser patterning of functional organic monolayers, prepared on oxide-free hydrogen-terminated silicon, and subsequent backfilling of the laser-written lines with a second organic monolayer that differs in its terminal functionality, is described. Since the thermal monolayer decomposition process is highly nonlinear in the applied laser power density, subwavelength patterning of the organic monolayers is feasible. After photothermal laser patterning of hexadecenyl monolayers, the lines freed up by the laser are backfilled with functional acid fluoride monolayers. Coupling of cysteamine to the acid fluoride groups and subsequent attachment of Au nanoparticles allows easy characterization of the functional lines by atomic force microscopy (AFM) and scanning electron microscopy (SEM). Depending on the laser power and writing speed, functional lines with widths between 1.1 µm and 250 nm can be created. In addition, trifluoroethyl-terminated (TFE) monolayers are also patterned. Subsequently, the decomposed lines are backfilled with a nonfunctional hexadecenyl monolayer, the TFE stripes are converted into thiol stripes, and then finally covered with Au nanoparticles. By reducing the lateral distance between the laser lines, Au-nanoparticle stripes with widths close to 100 nm are obtained. Finally, in view of the great potential of this type of monolayer in the field of biosensing, the ease of fabricating biofunctional patterns is demonstrated by covalent binding of fluorescently labeled oligo-DNA to acid-fluoride-backfilled laser lines, which--as shown by fluorescence microscopy--is accessible for hybridization.