Elsevier

Sensors and Actuators B: Chemical

Volume 239, February 2017, Pages 571-577
Sensors and Actuators B: Chemical

A smartphone based surface plasmon resonance imaging (SPRi) platform for on-site biodetection

https://doi.org/10.1016/j.snb.2016.08.061Get rights and content

Abstract

We demonstrate a surface plasmon resonance imaging platform integrated with a smartphone to be used in the field with high-throughput biodetection. Inexpensive and disposable SPR substrates are produced by metal coating of commercial Blu-ray discs. A compact imaging apparatus is fabricated using a 3D printer which allows taking SPR measurements from more than 20.000 individual pixels. Real-time bulk refractive index change measurements yield noise equivalent refractive index changes as low as 4.12 × 10−5 RIU which is comparable with the detection performance of commercial instruments. As a demonstration of a biological assay, we have shown capture of mouse IgG antibodies by immobilized layer of rabbit anti-mouse (RAM) IgG antibody with nanomolar level limit of detection. Our approach in miniaturization of SPR biosensing in a cost-effective manner could enable realization of portable SPR measurement systems and kits for point-of-care applications.

Introduction

The wide use of mobile phones all across the world created significant opportunities for healthcare applications using mobile devices. Improvement of healthcare services requires democratization of the services with higher quality and lower cost. Early diagnosis, close monitoring, patient comfort are some of the concerns that healthcare providers are striving to improve on. The development of lab-on-a-chip platforms in the last two decades brought several examples of novel platforms that can be used for rapid diagnosis of widespread diseases. Portability, short turn-around-time, cost-efficiency and connectivity are some of the critical assets that successful devices should possess. The advancements in such areas enabled the use of lab-on-a-chip systems as on-site or point-of-care systems not only for remote or resource-limited settings, but also for home-monitoring of elderly population at developed countries.

One of the main bottlenecks in transforming the lab-on-a-chip systems into point-of-care diagnostic devices is the requirement to miniaturize and combine several off-chip components. The marriage of the lab-on-a-chip systems with mobile phones was the tipping point that yielded a plethora of integrated screening and diagnostic devices. Mobile phones provide powerful CPUs, touch screen displays, advanced connectivity features as well as high pixel-count, sensitive cameras and integrated light sources. Therefore, the use of mobile phones for applications requiring optical detection is an interesting and rapidly developing field of research. For instance, immunodiagnostic assays, lateral flow assays, microscopic imaging, flow cytometry, colorimetric detection, photonic crystal and surface plasmon resonance (SPR) based biosensing have been demonstrated using mobile phone platforms [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12]. In this study, to the best of our knowledge we present the first surface plasmon resonance imaging on a smartphone.

SPR biosensing is a popular method for quantitative analysis and characterization of biomolecular interactions [13], [14], [15]. SPR provides label-free and real-time detection of binding events with high sensitivity. Surface plasmons are electromagnetic waves propagating along and evanescently decaying away from the metal/dielectric interface. This field confinement around the boundary makes plasmon resonance coupling condition extremely sensitive to the local refractive index changes caused by specific adsorption of target analytes onto the molecular probes residing on the metal surface. Recently, some studies have demonstrated SPR sensing using smartphone. Preechaburana et al. reported angle-resolved SPR chemical detection using an SPR coupler attached on the smartphone screen utilizing the illumination from the screen [8]. In order to develop a more practical system, Liu et al. [9] and Bremer et al. [10] showed the use of optical fibers for SPR detection on cell phones. Both of these systems used the back-side LED and camera of the cell phone as the light source and the sensor, respectively. Roche et al. demonstrated localized SPR sensing on cell phone with increased sensitivity using gold nanoparticles and nanorods [11]. Dutta et al. reported localized SPR (LSPR) sensing on cell phone for biomolecular detection and measuring size variation of metal nanoparticles [12]. All of these studies, demonstrate single-spot or 1D spatially resolved SPR sensing, which limits their applicability for high-throughput and multiplexed detection. In this article, we demonstrate SPR imaging or 2D SPR sensing on a cell phone, unveiling the potential of multi-analyte detection as well as implementation of array-based advanced biochemical analysis using a low-cost, integrated platform (See Supplementary material Table S1 for detailed comparison with previous studies).

SPR imaging is superior to single-spot SPR since it can be used for detection of multiple analytes in a single sample for panel assays. This leads to significant benefits in terms of cost and measurement time. Similarly, the multiple sensing points on the sensor can be used for detection of the analyte at several sample dilutions which is critical for serial dilution assays. Also, image-based bioanalytical detection helps the operator to view the results at once and interpret them more easily. Additionally, image-based 2D sensing can provide replicated measurements on the same sensor chip together with controls that leads to higher reliability, precision and on-chip self-calibration. On-chip control and self-calibration are especially critical for point-of-care sensing applications that suffer from high error rates due to varying operating conditions and the wide range of user levels. We believe the demonstration of such advanced biochemical techniques using mobile phones and cost-effective sensors will lead to a paradigm shift in the global healthcare market. Implementation of advanced detection applications on continuously improving feature-rich mobile phones will pave the way towards highly sensitive diagnosis tools reaching to the people from all socio-economic levels.

Here, we present surface plasmon resonance imaging on a smartphone. We have developed very low-cost grating coupled SPR sensor chips using off-the-shelf optical storage discs. Additionally, we designed a compact optical system, using a 3D-printed apparatus that hosts the LED source, collimator, bandpass filter, linear polarizer, beamsplitter plate and an external imaging lens which can be easily attached to the smartphone. We employed a silver/gold (Ag/Au) bilayer structure coated on the periodic corrugations of Blu-ray discs in order to perform plasmon resonance imaging at the central region of visible spectrum (λr ∼500 nm) under normal incidence illumination in aqueous environment. This allowed the optimal use of the CMOS sensor of the smartphone while maintaining high sensitivity, chemical stability and biological affinity [16], [17], [18], [19], [20]. A microfluidic channel is placed on the bimetallic layer for controlled plumbing of the liquids. The use of Blu-ray discs and standard metal deposition techniques together with the low-cost microfluidic channel resulted in significant cost-reduction which can allow the system to be used for applications requiring disposable SPR sensors.

Section snippets

Smartphone attachment for surface plasmon resonance imaging

An optical attachment was developed which converts smartphone into a real-time surface plasmon resonance imaging platform based on intensity interrogation mechanism. A Samsung I8552 Galaxy Win was used as the smartphone. The prototype accessory was fabricated out of polylactic acid (PLA) filament using a 3D printer (MakerBot Replicator 2). Optical configuration of the imaging platform is schematically illustrated in Fig. 1a. Light emitting from a 520 nm LED source is coupled to a multimode fiber

Microarray imaging of Ag/Au bimetallic sensing spots

We have performed SPR imaging of Ag/Au bimetallic microspot array under bulk dielectric media with changing refractive indices. The bimetallic microarray structure was fabricated using conventional optical lithography processes in addition to metal deposition steps. The diameter of each spot is 110 μm and the spacing between adjacent spots is 130 μm. First, we have recorded video of illuminated sensor surface at 30 frames/s during the successive flow of glycerol solutions with increasing

Conclusion

In this work, we demonstrated the use of a smartphone as a hand-held surface plasmon resonance imaging biosensor with high sensitivity. Developing an attachable imaging accessory from inexpensive optical components and 3D printed parts, and using easy-to-implement procedures for fabricating miniaturized sensor chips integrated with flow cells from extremely cheap substrates like optical storage discs, we offer a promising detection platform that enables biosensing in the field with high level

Acknowledgement

This work was supported by the State Planning Agency of the Turkish Republic Project UNAM.

Hasan Guner is a Ph.D. student at the UNAM Materials Science and Nanotechnology Program at Bilkent University. His research interests are in the field of design and implementation of plasmon resonance sensing systems.

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  • Cited by (0)

    Hasan Guner is a Ph.D. student at the UNAM Materials Science and Nanotechnology Program at Bilkent University. His research interests are in the field of design and implementation of plasmon resonance sensing systems.

    Erol Ozgur is a post-doctoral research associate at the UNAM Materials Science and Nanotechnology Program at Bilkent University. He currently works on large scale production and various applications of photonic and plasmonic biosensors.

    Guzin Kokturk is a researcher at the UEKAE − BILGEM − The Scientific and Technological Research Council of Turkey (TUBITAK). She works in Bioelectronics Devices and Systems Group. Her research interests are development of biosensor devices and biological assays for different biosensor application areas.

    Mehmet Celik is a Ph.D. student at the Department of Computer Engineering at Middle East Technical University. His research interests are in the field of computer vision and machine learning.

    Elif Esen is researcher at the UEKAE − BILGEM − The Scientific and Technological Research Council of Turkey (TUBITAK). She is a Ph.D. student at Molecular Biology, Genetics and Biotechnolgy program at the Istanbul Technical University and continues to work in the fields of biosensor device and sensor chip development.

    Ahmet Emin Topal is a Ph.D. student at the UNAM Materials Science and Nanotechnology Program at Bilkent University. His research interests are in the field of colorimetric biomolecular sensing and imaging using plasmon resonances.

    Sencer Ayas is a post-doctoral fellow at the Canary Center at Stanford for Cancer Early Detection, Department of Radiology, Stanford School of Medicine. His research is on the design and realization of plasmonic nanostructures and metasurfaces, with applications to imaging and spectroscopy.

    Yildiz Uludag is the Head of Computational Biology And Security Applications Unit at the UEKAE − BILGEM − The Scientific and Technological Research Council of Turkey (TUBITAK). She received her Ph.D. from Cranfield University (UK) and continues to work in the fields of biosensor device and sensor chip development.

    Caglar Elbuken is Assistant Professor at Bilkent University, National Nanotechnology Research Center. His research interests include lab-on-a-chip devices, microdroplet-based microfluidic systems and sensing technologies for portable applications.

    Aykutlu Dana is Associate Professor at Bilkent University, National Nanotechnology Research Center. He received his Ph.D. from Stanford University and continues to work in the fields of nanoscale optoelectronic devices and sensors.

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