Biosensors for Diagnostics

BioSensorssetupMEMS Biosensor  project is an ongoing multi-disciplinary project which is supported by  TUBITAK and INVENTRAM and aims to design, fabricate and test; easy to use, robust, portable, real-time, remote, low-cost and multi-analyte biosensing platforms. Various groups demonstrated that microcantilever technology can be used to detect up to zeptogram sensitivities. Project is mainly focused on biosensing with dynamic actuated µcantilever arrays which are fabricated with single mask lithography.

Actuation is achieved using thin-film ferromagnetic material as the cantilever material. Resonance frequency of the cantilevers are observed by utilizing the grating interferometric optical readout. Analyte mass accretion on cantilever shifts the resonance frequency of the µcantilever and analyte mass can be determined by the resonance frequency shift.

Actuation and readout mechanism is summarized in Fig. 1 With self-excitation, it is possible to oscillate multiple cantilevers without using an external signal generator and the resonance frequency shifts can be directly observed with frequency counting.  The realtime tracking of resonant frequency is conducted by a closed-loop PLL circuit. Dynamic Operation can be done either in liquid or air. Since the chip is remote and wireless, it can easily be disposable. Additionally, platform is demonstrated to be robust against refractive index fluctuations and mechanical vibrations. A custom flow-cell is designed and manufacturated at Koç University. The flow-cell minimizes the experimental error and enables integration of the biosensing platform into a hand-held, portable device.

Particular emphasis is applied to His tagged K-opioid protein, E-coli bacteria and Slicon bead. For His tagged K-opiod protein, it is shown that the minimum detectable concentration is 5.7ng/ml for an resonator frequency of 50kHz and with a bandwidth of 2Hz. This sensitivity can be also increased with averaging of multiple cantilever readout and further experiments. Furthermore by using the same approach the viscosity and density values of the media can be observed. The variation of the viscosities of different biological liquids are being measured with a high sensitivity using small sample volumes. Blood plasma and Serum viscosities can be measured with a sensitivity better than 0.03 cP using 50ul of sample.


Relevant Publications:

O. Cakmak, N. Kilinc, E.Ermek, A. Mostafazadeh, C. Elbuken, G.G. Yaralioglu, H. Urey “LoC Sensor Array Platform for Real-Time Coagulation Measurements ” accepted to IEEE MEMS 2014.

O. Cakmak, N. Kilinc, E.Ermek, G.G. Yaralioglu, H. Urey “MEMS Based Blood Plasma Viscosity Sensor Without Electrical Connections” in IEEE Sensors 2013,  Baltimore, Maryland, USA, November 2013.

N Kilinc, O Cakmak, A Kosemen, E Ermek, S Ozturk, Y Yerli, ZZ Ozturk, H Urey, “A Voc Sensor Based on Micromechanical Cantilever Functionalized with ZnO Nanorods”  The 17th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTas 2013), Freiburg, Germany, October 2013.

-Cakmak O, Elbuken C., Ermek E., Mostafazadeh A., Alaca B.E., Urey H., “Microcantilever Based Disposable Viscosity Sensor for Serum and Blood Plasma Measurements” Methods, 63 (2013) 225-232.

– O. Çakmak, Ç. Elbüken, E. Ermek, S. Bulut, Y. Kılınç, I. Barış, H. Kavaklı, E. Alaca, H. Ürey, ” MEMS biosensor for blood plasma viscosity measurements” New Biotechnology, 29, Supplement  S162-S163, 2012. (also published as Proceedings of the European Congress on Biotechnolgy Conference)

 Erman Timurdogan, Natali Ozber, Sezin Nargul, Serhat Yavuz, M. Salih Kilic, I. Halil Kavakli, Hakan         Urey, and B. Erdem Alaca, ” Detection of human K-opioid antibody using microresonators with integrated    optical readout,”  Biosensors and Bioelectronics, Vol. 26, pp. 195-201, 2010

 A. Ozturk, H. I. Ocakli, N. Ozber, H. Kavakli, H. Urey, E. Alaca, “A magnetically actuated resonant mass     sensor with integrated optical readout,”  Phot. Tech.. Lett., Vol. 20, 1905-1907, 2008



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