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Another recent example incorporates a fiber-optic SPR on the backside of a smartphone, the LED flash as light source, and the camera to capture the images that are processed by a specifically developed application to obtain relative intensity [ 48 ].
Journal of Applied Physics , 1 , Materials Research Express , 6 5 , A similar system based on transmission configuration has been recently presented by Cappi et al. Hui Pan. From chip-in-a-lab to lab-on-a-chip: towards a single handheld electronic system for multiple application-specific lab-on-a-chip ASLOC. Chinese Physics B , 26 2 , References [1].
The design incorporates a reference sensing channel to compensate fluctuations coming from the LED source. All the functionalities are integrated in the platform: flow cell, optics, illumination system, detection system, and software. Based on proof-of-concept biosensing, the authors show that the system performance is comparable to a conventional SPR instrument, demonstrating that this cost-effective, palm-sized version can provide interesting features and represent an attractive and affordable alternative for many on-field applications.
Moreover, although it is based in a Au-coated capillary, it would be possible to use nanostructures in the capillary for an LSPR version of the device. The detection configuration is based on surface plasmon-enhanced fluorescence spectroscopy rather than on detecting LSPR wavelength shift, which can significantly enhance sensitivity. The POC design contemplates a handheld-sized version using the mobile phone camera to detect the fluorescence and a desktop version using a high-resolution microscopic camera for enhanced performance.
The design incorporates disposable fluidics with either four or nine chambers controlled by micropumps to deliver the fluid. Although it requires fluorescent labels and the sensitivity of the handheld version is limited, the design incorporates the necessary software to operate automatically and contemplates all the aspects to have an affordable portable POC to be used in remote areas. Another example more elaborate from the biosensor point of view implements a label-free detection experiment for pesticide detection using Ag nanoslits and transmission measurements with a smartphone [ 50 ].
Although, in principle, it is a qualitative estimation based on naked-eye colorimetric detection, it can be further optimized with image processing to get more precisely semiquantitative analysis by developing spectrometric software for the smartphone and a POC design with integrated optics. Although many of the reported applications based on the use of LSPR-based biosensor still remain at a proof-of-concept level, some interesting results have recently appeared in fields ranging from food monitoring to disease diagnostics. Besides sensitivity issues that may be a limiting factor in some applications especially in the clinical area, the main problems are often related to the specificity and selectivity of the assays and the application to the analysis of real complex samples without previous pretreatment.
The advances in surface chemistry and biotechnology could help solve these challenges as addressed in some of the examples detailed below, which demonstrate real-life applications. The use of LSPR-based biosensors for food safety and environmental and pharmaceutical analysis is highly attractive for day-to-day decentralized monitoring for example, in the pharmaceutical field to discriminate enantiomers from a racemic mixture [ 51 ].
This is a crucial aspect because usually only one of the enantiomers is responsible for the desired physiological effects, whereas the other one may be inactive or even responsible for adverse effects. Using accurately selected weak receptors individually immobilized on a dual-channel microfluidic biosensor, both R - and S -1,2,3,4-tetrahydronaphthylamine TNA enantiomers were discriminated. With an LOD of n m and the possibility to develop a full portable system, it is a potential alternative to conventional chromatographic methods [ 51 ].
In the context of food safety, Park et al. However, it did not include setup development or microfluidics, as measurements were directly done with a conventional plate reader [ 52 ]. SadAbadi et al. This hormone is used in dairy farming to increase milk production. A biosensor based on Au nanoparticles immobilized in PDMS microfluidic channels in transmission configuration using a conventional spectrometer was employed for this purpose.
The microfluidic channel acts also as a reactor for the nanoparticle synthesis, leading to narrow size distribution and extinction spectra compared to those synthesized at macroscale [ 53 ]. However, the biosensor demonstration was rather limited, testing only biointeractions in buffer and omitting specificity and reproducibility studies. A more complete assay was developed by Ming et al. Although the biosensor scheme requires sample pretreatment for protein extraction and the assay is performed with a bulky platform, a low detection limit is achieved 4. An interesting example with on-site analysis has been recently provided by Lee at al.
Finally, there is a rising interest in the development of sensor platforms for the detection of biological hazards for risk assessment in food and for the detection of chemical and biological warfare agents. For instance, Nagatsuka et al. Natural glycosyl ceramides were used as specific receptors and immobilized on Au nanoparticles, which were previously attached to glass surfaces.
These carbohydrate molecules are known to bind microorganisms and biological toxins. The LSPR system based on transmission measurements can detect ricin, Shiga toxin, and cholera toxin with LODs of 30, 10, and 20 ng ml -1 , respectively, although the optimization of the assays is still limited.
It is in the biomedical field and in clinical diagnosis, in particular, where more efforts are concentrated. The development of efficient analytical tools for the fast and simple detection of disease-related biomarkers in human fluids or tissues can lead to earlier and more accurate diagnosis and prognosis as well as appropriate therapy monitoring. Early diagnosis commonly implies the detection of biomarkers at very low concentration; therefore, it requires high sensitivity, specificity, and fast analysis. Avoiding any treatment of the biological sample is also a must to push the analysis speed and the potential transfer to POC devices.
For label-free optical configuration such as in plasmonic-based devices, false positives commonly come from the nonspecific binding of either the target biomarker on the surface or the additional components present on the complex sample urine, saliva, blood, etc. Besides using high-quality bioreceptors to push specificity, it is extremely necessary to tune the properties of the bioactive layer to minimize both types of undesired bindings [ 56 ].
This process can become extremely complex, because it strongly depends on the nature of the sample, and in many cases, it is also difficult to extrapolate conditions from bioassay to bioassay. In most occasions, it becomes inevitable either to dilute the sample, reducing also the matrix interfering substance and subsequently worsening the detection capabilities, or to introduce a more elaborate pretreatment to extract the biomarker.
Nanoplasmonics: Advanced Device Applications provides a scientific and technological background of a particular nanoplasmonic application and outlines the. Request PDF on ResearchGate | Nanoplasmonics: Advanced device applications | Focusing on control and manipulation of plasmons at nanometer dimensions.
Both solutions, however, go into the detriment of POC-based devices and constitute the main reason why POC biosensors have not successfully reached the market yet. A work that deals with some of these aspects and attempts the detection in urine and serum is the one recently reported by Soler et al. In this work, they tested an oriented-based antibody immobilization strategy to bind proteins in a uniform and tight manner on Au nanodisks. The strategy was applied to the direct detection of protein biomarkers such as the human chorionic gonadotropin hCG , C-reactive protein CRP , and focal adhesion kinase FAK protein [ 14 ].
Direct detection in urine was demonstrated, keeping unaltered the LODs compared to buffer conditions, although for the analysis in serum it was necessary a dilution factor. Using the same setup, a biosensor for amoxicillin allergy diagnosis has been recently developed [ 13 ]. An extremely good LOD of 0. The samples from allergic patients were evaluated and validated with a conventional clinical immunofluorescence assay, confirming an excellent correlation between both techniques. Although multiplexing is not addressed yet in this configuration, these results represent an important step to fully functional biosensor platforms with high relevance for clinical diagnostics.
Using Ag nanoparticle arrays and extinction measurements, it was possible to detect a specific antigen related to cervical cancer squamous cell carcinoma antigen with excellent LODs 0.
Preliminary data collected from few cervical cancer patients indicate good potential for real sample detection. Other works have attempted multiplexed detection. The detection is based on a sandwich immunoassay, where a secondary specific antibody is added to increase the signal and to improve detectability.
Cytokines are secreted by immune cells and are related to the dynamic regulation of the immune system [ 58 ]. Their secretion and accurate quantification can help in determining changes or alterations in the immunosystem, such as inflammatory disease conditions [ 59 ], [ 60 ]. The interference of blood components is minimized by extracting the cells using microbeads. This novel approach, which combines advance microfluidics and the sensitivity levels of LSPR-based reflection measurements, reduces up to times the sample volume and up to three times the time required for the immunoassay compared to conventional enzyme-linked immunosorbent assay ELISA.
This represents a clear advantage of the microfluidic systems in which the evaluation times, the sample amount, and the pretreatment can be reduced. In a more recent study, the same authors developed a multiarrayed Au nanorod biosensor with capability for parallel multiplex immunoassays with the goal of monitoring up to six different cytokines in neonate complex serum matrix [ 62 ]. Although the detection is based in dark-field imaging which highly reduces the portability of the system , the potential of throughput is impressive: the multiarray has nanoplasmonic sensing spots 60 stripe-like segments in each of the eight microfluidic channels incorporated in the design of the array; see Figure 3B.
Moreover, besides assay optimization, results were validated with ELISA assays, showing excellent correlation. Even real serum samples from two neonate patients were tested to monitor the inflammatory response of infants before and after surgery. Serum for both patients was collected before surgery and afterwards for 4 consecutive days.
Although different degrees of response were observed in the two patients, the pattern was similar in both: increased levels on the first 2 days after surgery and a return to preoperative levels after day 3.
This proof-of-concept experiment demonstrates the capabilities of the LSPR platform to detect [ 62 ]. A Scheme of an integrated LSPR optofluidic platform that includes an Au nanostructured surface, a microfluidic chamber with in and out channels the chamber has integrated micropillar array to trap bead-bound target cells , and a top layer as structural support for light alignment and sample delivery.
A scheme representing the different steps of the process cell separation, incubation, and subsequent detection of secreted cytokines is also shown. Adapted and reprinted with permission from [ 35 ]. B Scheme showing the microfluidic design for the simultaneous detection of six cytokines with a nanorod microarray. It consists of eight parallel microfluidic channels each one with independent inlet and outlet for sample delivery, which are perpendicularly located to the nanoparticle array.
Subsequent antibody conjugation was done before removing the mask and incorporating the final one. The current chip design integrates AuNR microarray sensor spots, as can be seen in the final microarray chip layout 60 antibody-functionalized AuNR stripes segmented by 8 microfluidic detection channels. The obtained calibration curves are also shown.
Adapted and reprinted with permission from [ 36 ]. From left to right: Pictures of the Au nanoholes used as LSPR sensor, including an SEM image where the exosomes are captured by the antibody-coated surface, are shown; picture of the microfluidic cell with 12 independent channels and with three differentiated sensing areas; a photograph of the miniaturized imaging version of the setup, including the nPLEX chip.
The 3D-oriented Au nanoparticle substrate and the portable setup based on a disposable microfluidic chip with eight individual incubation chambers are shown. Images reproduced with permission from [ 61 ]. Scarce examples are found applying LSPR configuration to detect nucleic acids. Dodson et al. However, the study shows preliminary results, as it did not include any type of microfluidic cell, it involves static measurements, and no real samples or spiked complex samples have been assessed so far. A more elaborate work shows the detection of microRNAs miRNAs , which have become a very attractive family of biomarkers.
The authors use Au nanoprisms [ 64 ] and extinction evaluation, monitoring and quantifying the binding of an miRNA with a specific role in pancreatic cancer over complementary DNA sequences immobilized on the surface of the nanostructures.