SOI-Nanowire Biosensor for the Detection of Glioma-Associated miRNAs in Plasma

Abstract

Herein, we report the development of a highly sensitive nanotechnology-based system—silicon-on-insulator nanowire biosensor for the revelation of microRNAs (miRNAs), associated with the development of glioma in the human. In this system, a sensor chip, bearing an array of silicon nanowire structures, is employed. The sensor chip is fabricated using a top-down technology. In our experiments reported herein, we demonstrated the detection of DNA oligonucleotide (oDNA), which represents a synthetic analogue of microRNA-363 associated with the development of glioma. To provide biospecific detection of the target oligonucleotides, the surface of the nanowire structures is modified with oligonucleotide probes; the latter are complementary to the target ones. The concentration limit of the target oligonucleotide detection, attained using our nanowire biosensor, is at the level of DL~10−17 M. The revelation of the elevated level of glioma-associated miRNA in plasma is also demonstrated.

Raman Spectroscopy-Based Quality Control of “Silicon-On-Insulator” Nanowire Chips for the Detection of Brain Cancer-Associated MicroRNA in Plasma

“…To remove organic contaminants, the surface of the SOI-NW sensor chips was treated, as described elsewhere [ 32 , 41 , 42 ], with aqueous isopropanol solution, and then with a solution containing HF and ethanol (in order to remove the native oxide layer formed during the chip storage). After such a treatment, the chip was incubated in an ozonator (UV Ozone Cleaner–ProCleaner ™ Plus, BioForce Nanosciences, (Ossila Ltd., Sheffield, UK) in order to form hydroxyl groups on the SOI-NW surface, then it was silanized with APTES (as described in our previous papers [ 41 , 43 , 44 ]), washed with ethanol and dried [ 41 ].…”

“…In order to achieve biospecific interaction of the SOI-NW sensor surface with target oDNA/miRNA biomolecules, the surface of the NW sensors was sensitized with covalently immobilized oDNA probes, whose oligonucleotide sequence was complimentary to that of the target biomolecules. This procedure was performed similarly to that described in [ 41 ]. Namely, the immobilization was performed with using a preliminary activation of the chip surface with DTSSP crosslinker, and then ~0.6 nL microdrops of oDNA probes’ solutions (1 µM in 50 mM potassium phosphate buffer) were precisely dispensed onto the activated surface of individual SOI-NWs sensors with a Piezorray system (Perkin Elmer, Inc., Waltham, MA, USA).…”

“…Solutions of target oDNA were prepared from the initial 100 µM stock solution in 50 mM potassium phosphate buffer (pH 7.4) by serial tenfold dilution with working buffer (1 mM potassium phosphate buffer, pH 7.4) analogously to [ 41 ] and used in biosensor experiments immediately after preparation.…”

“…Electrical measurements were performed employing a ten-channel data acquisition and storage system (“Agama+” JSC, Moscow, Russia) similar to [ 41 ]. Time dependencies of the drain-source current I ds ( t ) were recorded in real time at V g = 40 V and V ds = 0.1 V [ 32 , 41 , 44 ].…”

Optical Monitoring of the Production Quality of Si-Nanoribbon Chips Intended for the Detection of ASD-Associated Oligonucleotides

“…The layout and characteristics of Si-NR chips, employed herein, were described in detail in our previous papers [ 27 , 28 , 29 ].…”