Use of nanostructures for biosensing has grown rapidly over the last several years,1 with promises of, for example, improved capabilities for life-sciences research, biomedical diagnostics for point-of-care treatment, and environmental monitoring. To date, much emphasis has been placed on development of nanostructured sensors, with comparatively less emphasis directed at facilitating analyte transport. For a nanostructured sensor to detect an analyte, such as disease-indicating biomarkers, that biomarker needs to be brought into contact with the sensor. The necessity of being small in scale limits the ‘reach’ of the sensor into the solution.
The primary approach to increasing analyte transport to surface-based sensors lies in application of microfluidics. Small-scale channels confine the analytes near the sensing surface and can thus confine boundary layers to increase the rate of diffusive transport. This approach works well for millimeter or larger-scale sensors, but not for nanostructured devices. The latter generally have a much smaller footprint. Downscaling from micro- to nanofluidic channels can improve transport at the sensor. However, this presents significant technical challenges, particularly at the relatively long (∼centimeter) lengths employed in most lab-on-a-chip systems. For example, nanofluidic channels are difficult to fabricate and prone to clogging, and require increased pressure to rapidly pump fluids through them because of their decreased channel size. One approach to solving this problem is to downscale to nanofluidic channels locally—at the sensor surface—and parallelize microfluidic flow into many channels. This would reduce flow resistance while increasing throughput. Here, we discuss our recent work on development and application of metal-film, flow-through nanoarray systems.2–4
Traditionally, nanohole-array sensors used dead-ended (blind) holes, or pits. Our through-hole arrays—see Figure 1(a)—enable fluid to flow through the film.4 This periodic array of nanoholes in the metal film exhibits extraordinary optical characteristics, where light transmission is amplified at specific wavelengths: see Figure 1(b). This is achieved, because the nanohole array permits only certain wavelengths to transmit through the structure. Surface plasmons play a central role in this process and ecourage their application to sensing. For exampe, surface-plasmon resonance, using the established Kretschmann configuration, is a common method for biosensing. However, these nanohole arrays in metal films present an alternative platform for surface-plasmon-based sensing, since they have a small footprint and can use a simple co-linear configuration of light source and detector. Additionally, our group4 and others5 have demonstrated up to one order of magnitude increases in sensor-response time using these structures.
Figure 1. (a) Schematic operation of a flow-through nanohole-array-based sensor incorporated into a diagnostic device. (b) Transmission of certain wavelengths (λ) of incident light by the flow-through nanoarray metal film.
The rate at which a sensor responds to a given sample depends on many things. Importantly, the analyte first needs to be transported to the surface, and the subsequent surface chemistry must proceed to binding. Therefore, flow-through nanohole arrays are helpful with respect to transport, but are not expected to influence surface-binding rates. Thus, flow-through nanohole arrays have an impact3 only in cases where transport is a limitation compared to traditional, surface-chemistry-based arrays. To show this, we performed scaling and computational analyses. We quantified the transport characteristics of the flow-through nanohole sensors using the collection efficiency. This metric is the fraction of analytes introduced into the device that are transported to the active sensing surface. Our flow-through nanohole arrays effectively demonstrated complete (>99%) collection of analyte at flow rates compatible with typical sensing schemes (∼10nl/s). At similar flow rates, an otherwise similar flow-over sensor—for example, with a similar active surface area—samples only a fraction of the analyte stream.
In summary, we have outlined our assessments of flow-though nanoarray sensors for improved analyte transport. Considering the challenges associated with moving analytes to small-scale sensors, flow-through nanohole arrays offer great promise. There are several exciting opportunities, for example development of fully multiplexed flow-through nanohole-array sensors in an on-chip format. To date, we have completed preliminary, proof-of-concept demonstrations of single sensors on relatively large chips. Another area of interest is the use of additional small-scale effects to improve the technology. For example, we are pursuing use of the strong capillary forces generated in the nanoholes to control wetting and enable localized surface functionalization. Also, we are studying use of an applied electric field and the resulting dynamics to concentrate charged analytes. We expect these new capabilities to add greatly to the optical properties and transport characteristics offered by flow-through nanohole arrays.
Funding support for this work from the Natural Sciences and Engineering Research Council (NSERC) of Canada, the Canada Research Chairs Program, Canada Foundation for Innovation, and British Columbia Knowledge Development Fund is gratefully acknowledged. The collaborative effort was funded through an NSERC Strategic Projects Grant, with the British Columbia Cancer Agency, and Micralyne Inc.
David Sinton, Carlos Escobedo
Department of Mechanical Engineering, University of Victoria
Department of Electrical and Computer Engineering, University of Victoria
Department of Chemistry, University of Victoria
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