Utilisation of micro- and nanoscaled materials in microfluidic analytical devices

Utilisation of micro- and nanoscaled materials in microfluidic analytical devices

Microchemical Journal 119 (2015) 159–168 Contents lists available at ScienceDirect Microchemical Journal journal homepage: www.elsevier.com/locate/m...

1MB Sizes 0 Downloads 74 Views

Microchemical Journal 119 (2015) 159–168

Contents lists available at ScienceDirect

Microchemical Journal journal homepage: www.elsevier.com/locate/microc

Review article

Utilisation of micro- and nanoscaled materials in microfluidic analytical devices Rastislav Monošík ⁎, Lúcio Angnes ⁎ Universidade de São Paulo, Instituto de Química, Av. Prof. Lineu Prestes 748, São Paulo, SP 05508-000, Brazil

a r t i c l e

i n f o

Article history: Received 26 October 2014 Received in revised form 3 December 2014 Accepted 3 December 2014 Available online 10 December 2014 Keywords: Microfluidics Microchannels Nanoparticles Microbeads Analysis

a b s t r a c t Microfluidic devices are receiving an increasing attention from scientific community and commercial sphere especially due to their potential to be low-cost, portable and practical handy analytical devices requiring extremely low volumes of samples and producing reduced amount of waste. Recently, nano- and microscaled particles have found wide application in the fabrication of microfluidic devices thanks to their ability to improve analytical performance. This review covers recent papers describing analytical microfluidic devices benefiting from nanoparticles or microbeads. Interesting concepts utilising magnetic properties of such particles were also included. Possible applications of these devices on analysis of real samples were considered and discussed. © 2014 Elsevier B.V. All rights reserved.

Contents 1. 2. 3. 4.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Microfluidics and microchannels . . . . . . . . . . . . . . . . . . . . Nanomaterials and microbeads . . . . . . . . . . . . . . . . . . . . . Application of nanoparticles and microbeads in microfluidic analytical devices 4.1. Magnetic nanoparticles, beads and powders . . . . . . . . . . . . 4.2. Carbon nanotubes and materials . . . . . . . . . . . . . . . . . 4.3. Gold nanoparticles . . . . . . . . . . . . . . . . . . . . . . . 4.4. Miscellaneous nano- and microsized particles . . . . . . . . . . . 5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Introduction The continuous increase in global production and implementation of various improvements in legislation regarding the safety and quality of products also brings new challenges into the associated subfields. Neither the proper production process nor quality control would be possible without disposing with an adequate analytical technique. Due to an increasing demand for time and cost effectiveness, there is an opportunity for new technologies to be preferred instead of conventional ⁎ Corresponding authors. E-mail addresses: [email protected] (R. Monošík), [email protected] (L. Angnes).

http://dx.doi.org/10.1016/j.microc.2014.12.003 0026-265X/© 2014 Elsevier B.V. All rights reserved.

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

159 160 160 161 161 162 162 164 166 166 166

ones. Such examples, which are the main subject of this review, are analytical devices utilising microfluidic technology. These microfluidic systems are often indicated in the literature as “micro total analysis systems” (μTAS) or “lab-on-a-chip” (LOC) systems [1,2]. Microfluidic devices are receiving a lot of attention both from the scientific community and commercial sphere, respectively, especially due to their ability to be miniaturised and thus to achieve favourable parameters for fabrication and final use. In recent years, nanoparticles and microparticles have often been introduced within microfluidics. Except for the fact of being a “fashionable” trend in modern scientific literature, there are obvious benefits legitimising their utilisation. Nanoparticles dispose with different (and in many cases with improved) properties compared to flat surfaces or

160

R. Monošík, L. Angnes / Microchemical Journal 119 (2015) 159–168

macroscaled particles. Moreover, their attractiveness is enhanced by the ability to be further modified or functionalised [3]. Microbeads are also utilised since they similarly allow surface modification, provide good surface-to-volume ratio for chemical binding [4] and applications such as chemical detection, cell encapsulation and drug delivery [5–7]. In this review, we discuss concrete examples of microfluidic devices utilising nanoparticles or microbeads designed for analytical purposes. Papers dealing with the utilisation of microfluidics solely for the synthesis of nanoparticles or microbeads are not included. The selection was predominantly focused on the last 5 years together with a few older papers presenting interesting and related concepts. Moreover, references for reviews focused on sub-topics discussed in detail are provided as well. 2. Microfluidics and microchannels One of the proposed definitions says that microfluidics is a state-ofthe-art technology which handles small volumes of liquids (10−9 to 10−18 L) being transferred within an area with dimensions of tens to hundreds of micrometres often called microchannels [8]. Thanks to these characteristics, microfluidic devices are suitable candidates for analytical purposes, since small volumes of reagents and samples are used. Also, low fabrication cost, in some cases biocompatibility, the possibility of miniaturisation, reduced volume of waste, easy customisation and transportation are other advantages. Thanks to these properties allowing microchannels to be practical handy devices, microfluidic chips may be applied in clinical diagnostics, especially in point-of-care testing [2,9,10], environment monitoring [11–13], food, agriculture and biosystems industries [14–16] or biochemical kinetic studies [17–19]. Although microchannels have numerous advantages and show a real potential for routine laboratory or in situ applications as illustrated in this review, their success within the commercial sphere is still minimal. Among the most serious reasons is most probably the insufficient verification and proper method validation in case of analyses of real samples and more complex matrices; poor or unverified analytical robustness of the whole system; fact that many devices were designed and tested only for one target analyte or utilising one enzymatic pathway (in case of enzyme-based measuring techniques); the necessity for additional detector and equipment or complicating scaling-up of the manufacturing process may also play a negative role in marketing plans. Microfluidic devices are conventionally made by etching or moulding microchannels into a working layer and then covered by another layer (Fig. 1). In practice, many microfabrication techniques were originally developed by the semiconductor industry. Silicon micromachining techniques started in the 1950s and have attained a high level of perfection since. Nevertheless, the degree of excellence of silicon

Fig. 1. Example of a microchannel device fabricated from poly(methyl methacrylate) (PMMA) by CO2 laser engraving.

micromachining techniques, the requirement of rapid prototyping of different microsystems allied with fact that silicon micromachining is a time consuming and expensive technique, drove the researchers to find new ways to construct microchannels using simpler procedures. Nowadays, the literature shows many alternative approaches for microchannel construction, including micromachining [20], soft lithographic micromoulding [21], hot embossing [22], laser ablation [23] or powder injection moulding [24]. A newer approach is represented by fabricating a layer with microchannels and integrated electrodes [25]. Microchannel devices made of thermoplastic polymers are less expensive than those made of glass, less adsorptive towards bio-molecules than polydimethylsiloxane (PDMS) and suitable to be mass-produced by hot embossing or injection moulding technologies [26]. Thermoplastic polymers such as polycarbonate (PC) [27,28], poly(methyl methacrylate) (PMMA) [29–31], and polystyrene (PS) [32] are the most commonly used materials. Low glass transition (LGT) polymers, such as PC and PMMA are not suitable for modification by the photolithography process, since high temperatures lead to deformation of the polymer material. However, a novel photolithography process using infrared radiation pre-baking for high precision metal patterning on LGT polymer substrates was recently introduced [33]. A creative method for the construction of microchannels was introduced by do Lago et al. [34] utilising a laser printer. The channel was printed directly on polyester film and the second layer of the same material was hot-pressed on this material. Alternatively, the microchannel was printed on the waxed paper and then the toner was transferred to glass or plexiglass surfaces. A second flat piece of the same material was fixed on the toner ink under heating and pressure [35,36]. Paper-based microchannels are also very popular as they are easy and cheap to prepare and their usage does not necessarily require expensive external devices or complicated arrangements [37–40]. 3. Nanomaterials and microbeads Nanoparticles (NPs) and nanotechnologies provide many benefits for electrochemical detection in biosensors [41–43], microfluidics or capillary electrophoresis [44–46]. Moreover, they can also be valuable for the fabrication of conductive matrices [47–49] or as a platform for enzyme [50,51] or for ligand immobilisation [52]. Large surface areas, chemical inertness and high electrical conductivity are properties that are beneficial for the purposes mentioned above. In particular the high surface area allows analytical characteristics such as lowering detection potential, increasing sensitivity, improving detection limits and stability to be enhanced [46]. There are many strategies that take advantage of nanoparticles in association with microfluidic devices. Magnetic nanoparticles (MNPs) provided an extra degree of flexibility, as their manipulation (e.g. stirring, positioning and recuperation) can easily be performed using a magnet of a magnetic inductor. The immobilisation of enzymes onto NPs is a challenge; as it is essential to preserve their catalytic activity and favourable conformation. The literature reveals many ways of connecting enzymes to different surfaces and MNPs containing immobilised enzymes, for example those containing cellulose [53] or lipase on their surface [54]. In both studies, it was observed that the immobilised enzymes had higher thermal stability and surprisingly superior activity compared with the free enzymes. Immobilised enzymes on MNPs were also utilised for organophosphate pesticide remediation [55]. A mutant form of the enzyme glycerophosphodiesterase was immobilised on the nanoparticles recovered with poly(amido amine) dendrimer using glutaraldehyde as a linking agent. The authors report the long-term stability of enzymes immobilised in this way, demonstrating that more than 95% of the response was retained after 120 days. MNPs functionalised with complexes containing terminals were explored to capture metal ions in solution and carry them to an electrode surface. In this case, the metals were electrodeposited and

R. Monošík, L. Angnes / Microchemical Journal 119 (2015) 159–168

the NPs were made ready for the next cycle. This procedure is much more efficient than classical electrodeposition reducing the number of steps compared with the conventional process [56]. As will be illustrated in the next section, great attention is also devoted to the utilisation of MNPs devices for advanced manipulation in microfluidics [57,58]. Nanomaterials were incorporated as the stationary phase in a lab-on-a-chip device for the first time in 2001 by Pumera et al. [59]. The glass microfluidics network was coated with a poly (diallyldimethylammonium chloride) carrying a positive charge, which enabled attachment to citrate-stabilised gold nanoparticles (GNPs). An overview discussing microfluidics benefiting from the use of nanomaterials for the enhanced separation and detection of analytes can be found in a study by Pumera [60]. In this review, microfluidics was also discussed in terms of synthesis and in terms of the simulation of environments for nanomotors and nanorobots. Another review by Medina-Sánchez et al. [61] focused on microfluidic platforms for synthesis, toxicity studies and characterisation of NPs. The integration of NPs into analytical devices for labelling, enhanced detection, and the in-chip process was also discussed. The paper provides references of the various strategies related to the use of NPs in microfluidics from dates prior to those included in our review. For those who are interested solely in the utilisation of carbon nanotubes (CNTs) in microfluidics, we recommend the review by Tey et al. [62]. This review shows advances in microfluidic-integrated CNTs and inorganic nanowires-based liquidgated field-effect transistor biosensors. Aspects of nanomaterial growth, device fabrication, sensing mechanisms, and interaction of biomolecules with nanotubes and nanowires were also addressed. Microbeads started to be explored in the first decades of the last century and for many applications were the precursor of the NPs. Microbeads can be prepared e.g. by monomer suspension polymerisation in a sealed polymerisation reactor [63] or using single emulsion droplet-based microfluidics technique as described in the work by Chen et al. [64]. In several applications (e.g. in the classical and in thin layer chromatography), microbeads and NPs can coexist. Some aspects of the use of NPs and microbeads in flowing solutions will be discussed in the next section. 4. Application of nanoparticles and microbeads in microfluidic analytical devices 4.1. Magnetic nanoparticles, beads and powders Magnetic nano- or microscaled particles dispose of advantages such as large surface-to-volume ratio or tunable anisotropic interaction, and also with the ability to be controlled by a magnetic field. Magnetic forces can be used for their transport, separation, positioning and organisation [65]. The magnetic field is usually applied from the microchannel exterior by means of permanent magnets or by an electromagnetic device. Lin et al. [66] implemented a solid-state sensor, micro-pump, and micro-valve into a PDMS microfluidic device to analyse pH level and glucose. An interesting feature was utilisation of magnetic powder (MP) together with glucose oxidase (GOx) contained in the alginate beads, which allowed beads to be further packed and immobilised at the sensing window of the EIS sensor. The magnetic powder was used to increase the signal by packing density of the beads on the sensor surface. In another work, Lin et al. [67], presented a model of a solid-state sensor-embedded microfluidic chip for the detection of glucose, urea and creatinine in human serum. Enzymes GOx, urease or creatinine deaminase were mixed with a sodium alginate solution and MP. The obtained mixture was loaded into a microfluidic-based pneumaticallydriven micro-vibrator [68] to generate tiny alginate micro-droplets into a thin corn oil layer. The temporarily formed alginate microdroplets were sunk into a sterile calcium ion solution to form jelled microbeads. The electrolyte–insulator–semiconductor (EIS) sensor

161

provided voltage signal due to the release of hydrogen ions from the enzymatic reaction. The positive aspect of this work is that the device was tested on real samples and a good correlation of results with a commercial kit was achieved (from 5 to 14%). The authors believe that this method may be applied to analyses of other blood indicators in the sample chip by replacing different types of enzyme in the alginate bead. Sheng et al. [69] constructed a microfluidic device utilising enzymemodified MNPs in its microchannel. GOx was covalently attached to the surface of MNPs and localised in the microchannel by applying an external magnetic field. The enzyme reactor retained 81% of its activity after three weeks of storage. Serum samples were directly tested using a sample fracture technique to achieve baseline separation from ascorbic acid and proteins. Zheng et al. [70] developed a magnetically active microfluidic device for chemiluminescence bioassays. In this work, enzyme-functionalised MNPs were prepared with two enzymes — peroxidase and GOx. For enzyme immobilisation, a conventional alcohol-based silanization procedure with 3-aminopropyl-triethoxysilane was used to prepare amine-terminated MNPs. Glutaraldehyde was applied to act as the cross-linker and spacer. Based on the results, the authors believe, that the proposed assay has the potential to be used for the quantification of organic compounds since many enzyme-catalysed reactions of organic compounds involve producing H2O. Magnetic beads (MBs) were used to immobilise enzymes and deliver them in a micro-channel designed for glucose and creatinine determination (Fig. 2). MBs were modified with carboxyl functional group to bind GOx (using 1-Ethyl-3-[3-dimethylaminopropyl] carbodiimide crosslinker) and beads with amino groups were used to bind with creatinine deaminase by means of glutaraldehyde. The device seems to be a promising tool, requiring low sample consumption for operation, allowing multi-target detection, and long-term enzyme preservation [71]. Agrawal et al. reported the development of an immunosensor chip comprised of a specially designed circular microchannel. The device utilised MNPs and an embedded miniature permanent magnet. The chip utilised “in-flow capturing” of Escherichia coli which were subsequently visually detected and quantified by the magnetic nanoparticle pre-concentration technique in a microchannel using an upright fluorescent microscope [72]. Lombardi and Dittrich [73] developed a technique based on MBs with a microfluidic device for segmented flow generation. MBs were used as a carrier for molecules as they are able to selectively bind them. In this case the concept was used for binding warfarin to human serum albumin. MBs were withdrawn during droplet splitting from one of the “daughter” droplets. This was achieved by placing a small magnet in close proximity to one of the microchannel outlets. Droplets were formed by introducing warfarin together with the bead suspension into a stream of mineral oil. This device also appears to be a handy tool for various applications, such as binding assays, kinetic studies, and single cell analysis, in which the rapid removal of a reactive component is required. Teste et al. [74] designed a microdevice for allergy diagnosis containing IgE capture nanoplatform with integrated magnetic core–shell nanoparticles. The device benefits from both their magnetic and colloidal properties. IgE from blood sera interacted in the colloidal phase thus increased the analyte capture kinetics since both immunological partners may diffuse during the immune reaction. The analyses were performed over 20 min using 5 μL of reagents. Lindsay et al. [75] developed the system utilising aqueous microdroplets containing MNPs moving in and out of a three-electrode assembly. The movement was controlled by external magnets placed below the superhydrophobic surface. The concept was used for the detection of dopamine by square-wave voltammetry. The ability of the proposed system to manipulate microliter volumes was also illustrated in bioassays of glucose. There, GOx and substrate droplets were merged,

162

R. Monošík, L. Angnes / Microchemical Journal 119 (2015) 159–168

Fig. 2. A) Scheme of the method (not to scale). Magnetic beads coated with human serum albumin (HSA_MBs) and the drug (warfarin) are injected into a stream of oil to form microdroplets. Daughter droplets are formed at the T-junction with identical volume, but unequal content, then exposed asymmetrically to a magnetic field. Measuring the free and total (bound + free) warfarin concentrations ([W]FREE and [W]TOTAL) in the outlets finally enables the determination of the association constant. B) Photograph of the microdevice with a one Euro coin for comparison (reproduced with permission from Lombardi and Dittrich [73]).

followed by chronoamperometric measurements of hydrogen peroxide produced during the course of the reaction. However, the working potential of + 650 mV used for peroxide detection and utilising GOx in a biochemical mechanism raised questions about its real potential for application in routine analyses of clinical samples since they were not tested in this work. 4.2. Carbon nanotubes and materials CNTs are known for disposing with unique high carrier mobility and conductivity, mechanical flexibility, and the potential for production at low cost [76]. Due to their composition and geometry, they display metallic and semiconducting electron transport properties and can store various molecules within their hollow interior [77]. They have found wide application in industry such as improving the quality of commercial products [78], and in analytical sciences [79] and had been proven to be suitable in particular for the immobilisation of proteins or nucleic acids [80,81]. Recently, Yu et al. covalently attached GOx to the carboxyl ends of the aligned single-walled CNTs and connected them via amid bonds to the surface of gold electrodes modified by amine groups. Biocompatible

ferrocenecarboxylic acid served as an electron transfer mediator. This array was intercalated into a PDMS-based microfluidic channel [82]. Bezuidenhout et al. [83] presented a method for integration of three-dimensionally sculptured nano- and microstructures into PDMS microchannels. Nanostructures were embedded in PDMS microchannels using a sacrificial resist process (Fig. 3). This technique allowed the implementation of an arrangement of structures in PDMS microchannels. The device was able to separate 6/10/20 kbp and 10/48 kbp DNA mixtures in a DNA fractionator containing glancing angle deposition (GLAD)-deposited SiO2 vertical posts as the separating medium. As the authors claim, GLAD fabrication enables the insertion of three-dimensional structures into microchannels that cannot be fabricated with any existing techniques, and this approach could be utilised in the development of other on-chip separation concepts. It was shown in the paper presented by Numthuam et al. [84] that 3D micropillar electrodes significantly improved the electric current detection compared to measurement on a planar electrode formed on the bottom of a microchannel. The reason for this was that the planar electrode was exposed to the lower amount of analyte due to its geometry while 3D micropillar arrangement disposed with a higher surface ratio. The applicability of the micropillar electrodes was tested in electrochemical enzyme-linked immunosorbent assay (ELISA) of bone metabolic marker proteins. During the ELISA experiments, it was found that there was no significant difference in the signal-to-noise ratio between the modified “3D” electrode and the “2D” electrode without modification. Yang et al. [85] used CNTs for immunoassay with the optical detection of Staphylococcal Enterotoxin B (SEB). The working principle involved four technologies, namely CNTs for primary antibody immobilisation, enhanced chemiluminescence (ECL) for light signal generation, a cooled charge-coupled device for detection and polymer lamination. An anti-SEB antibody-nanotube mixture was immobilised onto a polycarbonate strip to create a ligand surface that was bonded onto the microchannel device. SEB samples were detected by an ELISA system using peroxidase conjugated anti-SEB IgG as a secondary antibody and ECL. Wisitsoraat et al. [86] implemented functionalised CNT electrode in a PDMS/glass based flow injection microfluidic chip. Working CNTs, silver reference and platinum counter electrodes were placed on the chip by sputtering and low temperature chemical vapour deposition. Cholesterol oxidase was immobilised on CNTs by the in-channel flow technique. Interference studies showed low cross-sensitivities towards glucose, ascorbic acid, acetaminophen and uric acid. Graphene-based nanomaterials as electrochemical detectors in microchannel devices were tested by Chua et al. [87] Results obtained for graphene oxide amperometric detectors were compared with the results obtained at graphite microparticles and bare glassy carbon electrodes. According to the authors, there were no significant advantages of using graphene oxide as a detector in microfluidic devices and amperometric detectors based on graphite microparticles achieved an equivalent or even better performance. Tsuijita et al. [88] fabricated CNT amperometric chips by the combination of biosensors based on CNT-arrayed electrodes modified with GOx and microchannels with pneumatic micropumps made of PDMS. Pneumatic micropumps were employed to deliver phosphate buffer solution and potassium ferricyanide into the CNT electrodes. An analysis was performed electrochemically by differential pulse voltammetry. An advantage of this approach is the possibility to automatically exchange reagents on the CNT electrodes on each sensor. 4.3. Gold nanoparticles The utilisation of gold nanoparticles (AuNPs) is at the same time an old and very recent activity. In ancient times (probably accidentally prepared) gold nanoparticles were used to stain glasses. A classic example is the Lycurgus Cup, built in the 4th-century, which was able to change

R. Monošík, L. Angnes / Microchemical Journal 119 (2015) 159–168

163

Fig. 3. Process used to fabricate microchannels with embedded glancing angle deposition (GLAD)-deposited micro- and nanostructures. First, the GLAD nanostructures were deposited onto a clean, flat substrate. The porous film was filled with photoresist by spin application, and the resist was photolithographically patterned to define microfluidic channels. The entire substrate was coated with PDMS, which was then cured. Fluid reservoirs that also served as access holes for the sacrificial etch were punched or cut out of the PDMS. A sacrificial etch was used to remove the photoresist from the microfluidic channels, and the device was dried to complete the fabrication process (reproduced with permission from Bezuidenhout et al. [83]).

its colour, depending on the direction of the light. Throughout history, many other scientists report preparation of gold nanoparticles, between them Paracelsus and Faraday. In the middle of the last century, the first “recipe” to prepare gold nanoparticles was described by Turkevich et al.

[89] After 1990, with the popularisation of modern microscopes, many other methods were reported, some of which allowed researchers to prepare nanoparticles with a good control of size and forms, and elevated reproducibility [90–92].

Fig. 4. Pictures from the constructed microfluidic platform for the continuous monitoring of Hg(II). The constructed microfluidic device consists of two initial inlets for reagents, a bi-dimensional micromixer optical detection chamber and a collection channel to the outlet. Optical fibres are directly connected to the optical chamber by means of their insertion and glueing into two mechanized guides at both sides (reproduced with permission from Gómez-de Pedro et al. [94]).

164

R. Monošík, L. Angnes / Microchemical Journal 119 (2015) 159–168

An alternative way to prepare AuNPs was proposed by SadAbadi et al. [93] using PDMS microchannels; and afterwards, the device was used as a sensitive and low-cost localized surface plasmon resonance (SPR)-based biosensor for the detection of polypeptides. The biosensing experiment was based on the detection of antigen–antibody interaction of bovine growth hormones through the measurement of localized SPR spectra of the samples. In the study presented by Gomez-de-Pedro et al. (Fig. 4), AuNPs modified by a synthesised ionophore-based on a modified thiourea were used within the system designed for the monitoring of Hg(II). The interaction between AuNPs and heavy metal generated a change to the gold SPR band. The results revealed improved analytical characteristics compared to batch experiments [94]. Chung et al. [95] also developed a sensitive method for trace analysis of Hg(II) ions in water using a surface enhanced Raman scattering (SERS)-based microdroplet sensor. Aptamer-modified Au/Ag core– shell nanoparticles were used as sensing probes in the microdroplet channel. An oil phase was continuously flowing along the channel and was used to separate water droplets containing reagents from each other. The combination of a SERS-based microfluidic sensor with aptamer-based functional nanoprobes disposed with a small size and relatively simple design which suggests that it might be suitable for application in a real environment. AuNPs were used as a platform in a microfluidic immunosensor designed for the detection of IgG antibodies specific to Echinococcus granulosus in human serum samples. Gold electrode was modified by AuNPs to immobilise the E. granulosus antigen. Antibody–antigen interaction was quantified by peroxidase enzyme-labelled secondary antibodies specific to human IgG using catechol (Q) as an enzyme mediator. Results were obtained within 26 min which is shorter than the time required when using conventional methods [96]. AuNPs were also utilised by Cheong et al. [97] to transform infrared energy into thermal energy in a microfluidic chip. The resulting heat caused pathogen lysis. Afterwards, the DNA could be extracted from the cell body and transferred to a PCR system. This principle allowed a one-step real-time PCR system for pathogen detection without removing or changing the reagents. Another example of the utilisation of AuNPs within microfluidic technique was demonstrated by Luo et al. [98]. The assay was fabricated by deposition of AuNPs coated with protein antigens in the presence of their corresponding antibodies to a microfluidic channel surface. The system was used for the detection of goat anti-human IgG and only 30 ng of protein was required. Prabhakar and Mukherji [99] designed a chip for the detection of minor variations in the refractive index of its microenvironment, which is suitable for use as an affinity biosensor. This optical waveguide based sensor utilised localized SPR of AuNPs coated on a C-shaped polymer waveguide. The absorbance signal was obtained due to the localized SPR of SU8 (a commonly used epoxy-based negative photoresist) waveguide-bound AuNPs. The topic of utilisation of AuNPs in microfluidic immunoassays was discussed deeply in the review by Chen et al. [100]. 4.4. Miscellaneous nano- and microsized particles An example of the utilisation of Ag@SiO2 NPs was demonstrated in the system consisting of a microfluidic chip electrophoresis and a laser induced fluorescence device. Core-shell Ag@SiO2 NPs were immobilised onto the surface of the microchannel to increase the fluorescence intensity. The system was used to analyse reactive oxygen species (ROS) in puffs of cigarette smoke. Determination of ROS was based on the amount of 2′, 7′-dichlorofluorescein that had been loaded on polyacrylonitrile nanofibers in a micro-column and which trapped the ROS [101]. Zhang et al. [102] presented a microfluidic bead-based nucleic acid sensor for the detection of circulating tumour cells in blood samples.

The device utilised multienzyme-nanoparticle amplification and quantum dot (QDs) labels. Microbeads were functionalized with the capture probes and proteins localised inside the microfluidic channel acted as sensing elements. The AuNPs functionalised with the HRP and DNA probes were used as labels. The microfluidic device may be considered as a sensor platform for disease-related nucleic acid molecules. The integration of nanostructured metal oxide with a microfluidics device was presented by Ali et al. [103]. A microfluidics electrochemical cholesterol biosensor was based on a nanocrystalline anatase-titanium dioxide film deposited onto indium tin oxide (ITO) glass. The PDMS microchannel was fabricated using the standard procedures of soft lithography. Nanoparticles implemented in this device were able to directly communicate with the active sites of cholesterol oxidase and act as an electron mediator from active sites of the enzymes to the ITO electrode surface. Taylor et al. [104] reported the first integrated chip based microfluidic device combining pressure driven separation with real time SERS detection. The function of this device was to allow high performance analyte separations followed by SERS detection of analytes during continuous monitoring. A diffusive mixing region was introduced in which the chromatographic system consisted of a pillar array separation column followed by a reagent channel for passive mixing of a silver colloidal solution into the eluent stream to perform SERS with minimal sample manipulation. However, the authors claim that colloidal systems are usually less reproducible than SERS substrates prepared using deterministic patterning techniques. To verify the applicability of this system, only a mixture of benzenethiol and rhodamine 6G was used. The proposed system will probably require further testing to demonstrate its applicability on real samples. Tavares et al. [105] modified the surface of a glass-PDMS microfluidic channel by semiconductor QDs for the quantitative determination of nucleic acids. Electro-osmotic flow within channels was used for the delivery and subsequent immobilisation of QDs. Oligonucleotide probe sequences were deposited on the QDs by electrophoresis within a few minutes. The QDs were energy donors in fluorescence resonance energy transfer for transduction of nucleic acid hybridization. An analytical signal was obtained as the result of an emission from a fluorescent dye (Cy3) injected into the microchannel and its subsequent hybridisation. An interesting application of microdevices for multimodality microscopy imaging was demonstrated by a vertical scan of live cells in epi-fluorescence. Luo et al. [106] designed ultraflat and ultrathin PDMS hybrid microdevices to provide optical imaging for on-chip superlocalisation and the high-resolution imaging of single molecules and nanoparticles. The performance was validated by detailed monitoring of micronecklaces made of fluorescent microtubules and AuNPs. The activation and excitation cycles of single Alexa Fluor 647 dyes for direct stochastic optical reconstruction were also demonstrated. Jang and Koh [107] prepared an enzymatic assay within a microfluidic device using shape-coded poly(ethylene glycol) hydrogel microparticles. The microfluidic device was constructed by serially connecting two patterning chambers and a microfilter-integrated detection chamber through a Y-shaped microchannel. Microfilter was inserted inside the detection chamber for retaining hydrogel microparticles. Glucose and ethanol were simultaneously detected by means of bienzymatic reactions involving GOx and peroxidase or alcohol oxidase coupled with peroxidase together with Amplex Red within the hydrogel microparticles. Kim et al. [108] also connected chambers via microchannels. The first chamber was used for the reaction between analytes and enzymes, and the second was used for the quantitative analysis. The reaction chamber was filled with glass MBs covalently modified with GOx via aminopropyltriethoxysilane. In the detection chamber, a poly(ethylene glycol)-based peroxidase-entrapping hydrogel microarray was made by photolithography. This was used for the immobilisation of enzymes or fluorescent dyes for the optical analysis of enzyme-catalysed reactions.

Table 1 Summary of selected microfluidic devices utilising nano- and microscaled materials (MNPs — magnetic nanoparticles; MBs — magnetic beads; CNTs — carbon nanotubes; AuNPs — gold nanoparticles). Detected analyte or application

Detection limit

Linear range

Real samples analysis

Ref.

MNPs

Glucose, H2O2

Up to 2 mmol L−1 for glucose

Soft drinks

[70]

MNPs MNPs

Glucose Allergy diagnosis (IgE quantitation)

50 μmol L−1 glucose, 0.5 H2O2 μmol L−1 11 μmol L−1 1 ng mL−1

Human serums Human serums

[69] [74]

MBs

Glucose and creatinine

Not defined

human serum

[71]

MBs

Not applicable

Not applicable

[73]

Magnetic powder and alginate microbeads Aqueous drops containing paramagnetic iron particles Magnetic powder Single-walled CNTs arrays Various three-dimensionally sculptured nano- and micro-structures CNTs

Characterisation of the warfarin–human serum albumin-binding process Glucose, urea and creatinine Dopamine and glucose

From 25 μmol L−1 to 15 mmol L−1 1–30; 30–300; 30–1000 ng mL−1 (depending on the incubation time) 2–8 mmol L−1 for glucose 0.01 to 10 mmol L−1 for creatinine Not applicable

Human blood sample None

[67] [75]

pH and glucose Glucose DNA separation by fractionation in a pulsed electric field Staphylococcal Enterotoxin B

2 mmol L−1 Not defined Not applicable

2–8; 1–16 and 0.01–10 mmol L−1 26.4–132 μmol L−1 for dopamin, non-linear for glucose 2–8 mmol L−1 Up to 5 mmol L−1 Not applicable

None None Separation of DNA mixtures (sizes between 6 kbp and 48 kbp) Soy milk

[66] [82] [83]

Micropillar electrodes with nanoporous gold-black CNTs CNTs AuNPs AuNPs AuNPs

Bone metabolic marker proteins BAP and TRACP-5b Cholesterol Glucose Mercury(II) ions Bovine somatotropin (bST) Detection of circulating tumour cells

Not provided

None

[84]

10 mg dL Not provided 11 ppb 3.7 ng mL−1 1 HT29 in 1 mL

50–400 mg dL 5–20 mg mL−1 Not provided 2–80 ng mL−1 Not linear

[86] [88] [94] [93] [102]

Au/Ag core–shell nanoparticles AuNPs

Mercury(II) ions Determination of immunoglobulin G anti-Echinococcus granulosus antibodies DNA extraction and real-time PCR detection of pathogens Reactive oxygen species (2′,7′-dichlorofluorescein) Cholesterol Simultaneous detection of glucose and ethanol Glucose detection Glucose detection

Below 10−011 mol L−1 0.091 ng mL−1

10−6 to 10−11 mol L−1 0.5 and 115 ng mL−1

None None None none Spiked colorectal cancer cell lines HT29 in the blood Drinkable water Human serum

Not applicable

Not applicable

E. coli cells

[97]

5.5 × 10−11 mol L−1

0.055 to 8.2 nmol L−1

Cigarette smoke

[101]

AuNPs Ag@SiO2 Ag core–shell nanoparticles Nanocrystalline anatase-titanium dioxide Poly(ethylene glycol) hydrogel microparticles Glass microbeads Hydrogel microparticles

2; 16 and 0.01 mmol L−1 Not defined

0.1 ng mL−1

−1

0.5–5 ng mL−1 (defined only for immunosensor without CNTs) Up to 30 and 50 U L−1 −1

−1

[85]

[95] [96]

Not provided Not provided

1.3–10.3 mmol L 1.0–10 mmol L−1 for both

None None

[103] [107]

Not provided Not provided

1.00–10.00 mmol L−1 1.00–10.00 mmol L−1

None None

[108] [109]

R. Monošík, L. Angnes / Microchemical Journal 119 (2015) 159–168

Type of used nano-and micromaterial

165

166

R. Monošík, L. Angnes / Microchemical Journal 119 (2015) 159–168

Therefore, the measuring principle was based on a bienzymatic reaction, which resulted in the conversion of non-fluorescent Amplex Red into fluorescent resorufin within the hydrogel microarray. An interesting concept composed of a polymerisation and reaction chamber serially connected through the microchannel was presented by Choi et al. [109]. Hydrogel microparticles (HM) were fabricated inside the polymerisation chamber by photopatterning and subsequently transferred to the reaction chamber by pressure-driven flow. HM were used for the encapsulation of enzymes without affecting their activity and glucose was detected by sequential bienzymatic reaction involving hydrogel-entrapped GOx and peroxidase employing fluorescence method. The main advantage of this concept seems to be that microparticles are easily controlled during the photopatterning process in the interior compared to their external injection. Analytical characteristics of microfluidic devices described in this work are summarised in Table 1. As can be seen, most of the electrochemical devices are developed for glucose analysis using GOx while the measuring principle is often based on hydrogen peroxide detection. It is caused mainly by the fact that GOx is a stable, commercially available and price affordable enzyme and the importance of detecting glucose in blood is often pointed out as one of the main reasons. However, it should be mentioned that certain molecules in the body such as ascorbic acid or uric acid can undergo oxidation at the same applied potential as hydrogen peroxide and thus interfere with measurements [110]. Therefore, it is very important to pay attention to the interference studies as well as to compare results with those obtained by other, often better conventional and validated methods. 5. Conclusion Microfluidic analytical devices, so called “micro total analysis systems” or “lab-on-a-chip” systems are interesting especially due to their size, low-cost expenses for fabrication, low sample and waste volume consumption and portability. As also demonstrated in this review, microfluidic devices have the potential and ability to be applied for the analysis of food or clinical samples, environmental monitoring or for biochemical research. Utilisation of nanomaterials was shown to be beneficial and improved the analytical performance of microfluidic devices. This was especially thanks to superior surface-to-volume ratio for chemical binding compared to flat surfaces or macroscaled particles, the ability to be further modified or functionalized on their surface, and suitability for applications such as chemical detection, cell encapsulation, and drug delivery. On the other hand, it is important to point out that the majority of concepts demonstrated in the literature have so far not been used for real application. First of all, most of them were tested on simple synthetic samples. Without verification of their applicability by analyses of complex matrixes rather than just standard solutions prepared in water and without comparison with the reference validated methods, their applicability remains questionable. Another problem maybe is that most of the models were designed for glucose detection using glucose oxidase but have never been tested with more complicated enzymatic pathways. Fabrication process is not always simple and trouble-free, which can be an obstacle for investors when choosing a particular concept for mass production. Usage of an expensive detector (e.g. potentiostat, spectrophotometer or UV), which has to be coupled with a microchannel, can negate the primary advantage regarding cost. In conclusion, the development of microfluidic analytical devices requires much more research to attain the expected utilisation. Currently, the mass production of devices for rapid screening of multi-reagent samples is still relatively far from reality. Acknowledgements The authors are grateful for the financial support from the Brazilian Foundations: CNPq, (process 306504-2011-1) and FAPESP (process 2013/00972-2).

References [1] M.L. Kovarik, D.M. Ornoff, A.T. Melvin, N.C. Dobes, Y. Wang, A.J. Dickinson, P.C. Gach, P.K. Shah, N.L. Allbritton, Micro total analysis systems: fundamental advances and applications in the laboratory, clinic, and field, Anal. Chem. 85 (2013) 451–472. [2] C.D. Chin, V. Linder, S.K. Sia, Commercialization of microfluidic point-of-care diagnostic devices, Lab Chip 12 (2012) 2118–2134. [3] L.S. Wang, R.Y. Hong, Synthesis, surface modification and characterisation of nanoparticles. Advances in nanocomposites — synthesis, characterization and industrial applications, in: B. Reddy (Ed.)Synthesis, Surface Modification and Characterisation of Nanoparticles. Advances in Nanocomposites — Synthesis, Characterization and Industrial Applications, InTech,, 2011, pp. 289–322. [4] D. Kim, A.E. Herr, Protein immobilization techniques for microfluidic assays, Biomicrofluidics 7 (2013) 41501. [5] K. Liu, Y. Deng, N. Zhang, S. Li, H. Ding, F. Guo, W. Liu, S. Guo, X.-Z. Zhao, Generation of disk-like hydrogel beads for cell encapsulation and manipulation using a droplet-based microfluidic device, Microfluid. Nanofluid. 13 (2012) 761–767. [6] D.C. Appleyard, S.C. Chapin, R.L. Srinivas, P.S. Doyle, Bar-coded hydrogel microparticles for protein detection: synthesis, assay and scanning, Nat. Protoc. 6 (2011) 1761–1774. [7] M. Alagusundaram, S.C.C. Madhu, K. Umashankari, V.B. Attuluri, C. Lavanya, S. Ramkanth, Microspheres as a novel drug delivery system — a review, Int. J. ChemTech Res. 1 (2009) 526–534. [8] G.M. Whitesides, The origins and the future of microfluidics, Nature 442 (2006) 368–373. [9] J. Do, S. Lee, J.Y. Han, J.H. Kai, C.C. Hong, C.A. Gao, J.H. Nevin, G. Beaucage, C.H. Ahn, Development of functional lab-on-a-chip on polymer for point-of-care testing of metabolic parameters, Lab Chip 8 (2008) 2113–2120. [10] V. Srinivasan, V.K. Pamula, R.B. Fair, An integrated digital microfluidic lab-on-achip for clinical diagnostics on human physiological fluids, Lab Chip 4 (2004) 310–315. [11] J.C. Jokerst, J.M. Emory, C.S. Henry, Advances in microfluidics for environmental analysis, Analyst 137 (2012) 24–34. [12] A. Mehta, H. Shekhar, S.H. Hyun, S. Hong, H.J. Cho, A micromachined electrochemical sensor for free chlorine monitoring in drinking water, Water Sci. Technol. 53 (2006) 403–410. [13] L. Marle, G.M. Greenway, Microfluidic devices for environmental monitoring, TrAC Trends Anal. Chem. 24 (2005) 795–802. [14] M. Kamruzzaman, A.-M. Alam, K.M. Kim, S.H. Lee, Y.H. Kim, G.-M. Kim, T.D. Dang, Microfluidic chip based chemiluminescence detection of L-phenylalanine in pharmaceutical and soft drinks, Food Chem. 135 (2012) 57–62. [15] J.-Y. Yoon, B. Kim, Lab-on-a-chip pathogen sensors for food safety, Sensors 12 (2012) 10713–10741. [16] S. Neethirajan, I. Kobayashi, M. Nakajima, D. Wu, S. Nandagopal, F. Lin, Microfluidics for food, agriculture and biosystems industries, Lab Chip 11 (2011) 1574–1586. [17] D. Voicu, C. Scholl, W. Li, D. Jagadeesan, I. Nasimova, J. Greener, E. Kumacheva, Kinetics of multicomponent polymerization reaction studied in a microfluidic format, Macromolecules 45 (2012) 4469–4475. [18] C. Shao, B. Sun, M. Colombini, D.L. DeVoe, Rapid microfluidic perfusion enabling kinetic studies of lipid ion channels in a bilayer lipid membrane chip, Ann. Biomed. Eng. 39 (2011) 2242–2251. [19] P.L. Urban, D.M. Goodall, N.C. Bruce, Enzymatic microreactors in chemical analysis and kinetic studies, Biotechnol. Adv. 24 (2006) 42–57. [20] H. Qi, T. Chen, L. Yao, T. Zuo, Micromachining of microchannel on the polycarbonate substrate with CO2 laser direct-writing ablation, Opt. Lasers Eng. 47 (2009) 594–598. [21] B. Chen, K. Lu, K. Ramsburg, ZnO submicrometer rod array by soft lithographic micromolding with high solid loading nanoparticle suspension, J. Am. Ceram. Soc. 96 (2013) 73–79. [22] J.J. He, N. Li, N. Tang, X.Y. Wang, C. Zhang, L. Liu, The precision replication of a microchannel mould by hot-embossing a Zr-based bulk metallic glass, Intermetallics 21 (2012) 50–55. [23] C. De Marco, S.M. Eaton, R. Martinez-Vazquez, S. Rampini, G. Cerullo, M. Levi, S. Turri, R. Osellame, Solvent vapor treatment controls surface wettability in PMMA femtosecond-laser-ablated microchannels, Microfluid. Nanofluid. 14 (2013) 171–176. [24] J.H. Meng, N.H. Loh, G. Fu, B.Y. Tay, S.B. Tor, Micro powder injection moulding of alumina micro-channel part, J. Eur. Ceram. Soc. 31 (2011) 1049–1056. [25] X. Li, F. Zhang, J. Shi, L. Wang, J.-H. Tian, X.-T. Zhou, L.-M. Jiang, L. Liu, Z.-J. Zhao, P.-G. He, Y. Chen, Microfluidic devices with disposable enzyme electrode for electrochemical monitoring of glucose concentrations, Electrophoresis 32 (2011) 3201–3206. [26] Y. Wang, Q. He, Y. Dong, H. Chen, In-channel modification of biosensor electrodes integrated on a polycarbonate microfluidic chip for micro flow-injection amperometric determination of glucose, Sensors Actuators B Chem. 145 (2010) 553–560. [27] P. Jankowski, D. Ogonczyk, L. Derzsi, W. Lisowski, P. Garstecki, Hydrophilic polycarbonate chips for generation of oil-in-water (O/W) and water-in-oil-inwater (W/O/W) emulsions, Microfluid. Nanofluid. 14 (2013) 767–774. [28] D. Ogonczyk, J. Wegrzyn, P. Jankowski, B. Dabrowski, P. Garstecki, Bonding of microfluidic devices fabricated in polycarbonate, Lab Chip 10 (2010) 1324–1327. [29] L.M. Cerdeira Ferreira, E.T. da Costa, C.L. do Lago, L. Angnes, Miniaturized flow system based on enzyme modified PMMA microreactor for amperometric determination of glucose, Biosens. Bioelectron. 47 (2013) 539–544. [30] H.-H. Hou, Y.-N. Wang, C.-L. Chang, R.-J. Yang, L.-M. Fu, Rapid glucose concentration detection utilizing disposable integrated microfluidic chip, Microfluid. Nanofluid. 11 (2011) 479–487.

R. Monošík, L. Angnes / Microchemical Journal 119 (2015) 159–168 [31] M.R.F. Cerqueira, D. Grasseschi, R.C. Matos, L. Angnes, A novel functionalisation process for glucose oxidase immobilisation in poly(methyl methacrylate) microchannels in a flow system for amperometric determinations, Talanta 126 (2014) 20–26. [32] Y. Wang, J. Balowski, C. Phillips, R. Phillips, C.E. Sims, N.L. Allbritton, Benchtop micromolding of polystyrene by soft lithography, Lab Chip 11 (2011) 3089–3097. [33] Z.H. Huang, B.C. Lim, Z.F. Wang, Process development for high precision metal patterning on low glass transition polymer substrates, Microelectron. Eng. 98 (2012) 528–531. [34] C.L. do Lago, H.D.T. da Silva, C.A. Neves, J.G.A. Brito-Neto, J.A.F. da Silva, A dry process for production of microfluidic devices based on the lamination of laser-printed polyester films, Anal. Chem. 75 (2003) 3853–3858. [35] C.L. do Lago, C.A. Neves, D.P. de Jesus, H.D.T. da Silva, J.G.A. Brito-Neto, J.A.F. da Silva, Microfluidic devices obtained by thermal toner transferring on glass substrate, Electrophoresis 25 (2004) 3825–3831. [36] W.K.T. Coltro, J.A.F. da Silva, H.D.T. da Silva, E.M. Richter, R. Furlan, L. Angnes, C.L. do Lago, L.H. Mazo, E. Carrilho, Electrophoresis microchip fabricated by a directprinting process with end-channel amperometric detection, Electrophoresis 25 (2004) 3832–3839. [37] A.K. Yetisen, M.S. Akram, C.R. Lowe, Paper-based microfluidic point-of-care diagnostic devices, Lab Chip 13 (2013) 2210–2251. [38] X. Chen, J. Chen, F. Wang, X. Xiang, M. Luo, X. Ji, Z. He, Determination of glucose and uric acid with bienzyme colorimetry on microfluidic paper-based analysis devices, Biosens. Bioelectron. 35 (2012) 363–368. [39] X. Li, D.R. Ballerini, W. Shen, A perspective on paper-based microfluidics: current status and future trends, Biomicrofluidics 6 (2012). [40] D.D. Liana, B. Raguse, J.J. Gooding, E. Chow, Recent advances in paper-based sensors, Sensors 12 (2012) 11505–11526. [41] L. Ding, A.M. Bond, J. Zhai, J. Zhang, Utilization of nanoparticle labels for signal amplification in ultrasensitive electrochemical affinity biosensors: a review, Anal. Chim. Acta. 797 (2013) 1–12. [42] A.S.L. Roberto, R.M. Iost, F.N. Crespilho, Nanobioelectrochemistry. Implantable Biosensors to Green Power Generation, in: F.N. Crespilho (Ed.), Springer, Berlin Heidelberg, 2013, pp. 27–48. [43] J.B. Haun, T.J. Yoon, H. Lee, R. Weissleder, Magnetic nanoparticle biosensors, Wiley Interdiscip. Rev.-Nanomed. Nanobiotech. 2 (2010) 291–304. [44] M.J.A. Shiddiky, E.J.H. Wee, S. Rauf, T. M., Microfluidics, Nanotechnology and Disease Biomarkers for Personalized Medicine Applications, Nova Science Publishers Inc., 2013 [45] C.S.S.R. Kumar, Microfluidic Devices in Nanotechnology: Applications, Wiley-VCH, Verlag, 2010. [46] M. Pumera, A. Escarpa, Nanomaterials as electrochemical detectors in microfluidics and CE: fundamentals, designs, and applications, Electrophoresis 30 (2009) 3315–3323. [47] R. Monosik, M. Stredansky, G. Greif, E. Sturdik, A rapid method for determination of L-lactic acid in real samples by amperometric biosensor utilizing nanocomposite, Food Control 23 (2012) 238–244. [48] R. Monosik, M. Stred'ansky, G. Greif, E. Sturdik, Comparison of biosensors based on gold and nanocomposite electrodes for monitoring of malic acid in wine, Cent. Eur. J. Chem. 10 (2012) 157–164. [49] R. Monosik, M. Stred'ansky, E. Sturdik, A biosensor utilizing L-Glutamate dehydrogenase and diaphorase immobilized on nanocomposite electrode for determination of L-glutamate in food samples, Food Anal. Methods 6 (2013) 521–527. [50] S. Wang, P. Su, J. Huang, J. Wu, Y. Yang, Magnetic nanoparticles coated with immobilized alkaline phosphatase for enzymolysis and enzyme inhibition assays, J. Mat. Chem. B 1 (2013) 1749–1754. [51] K. Min, J. Kim, K. Park, Y.J. Yoo, Enzyme immobilization on carbon nanomaterials: loading density investigation and zeta potential analysis, J. Mol. Catal. B Enzym. 83 (2012) 87–93. [52] D. Grasseschi, V.M. Zamarion, K. Araki, H.E. Toma, Surface enhanced Raman scattering spot tests: a new insight on Feigl's analysis using gold nanoparticles, Anal. Chem. 82 (2010) 9146–9149. [53] Y. Li, X.-Y. Wang, R.-Z. Zhang, X.-Y. Zhang, W. Liu, X.-M. Xu, Y.-W. Zhang, Molecular imprinting and immobilization of cellulase onto magnetic Fe3O4@SiO2 nanoparticles, J. Nanosci. Nanotechnol. 14 (2014) 2931–2936. [54] W. Liu, F. Zhou, X.-Y. Zhang, Y. Li, X.-Y. Wang, X.-M. Xu, Y.-W. Zhang, Preparation of magnetic Fe3O4@SiO2 nanoparticles for immobilization of lipase, J. Nanosci. Nanotech. 14 (2014) 3068–3072. [55] L.J. Daumann, J.A. Larrabee, D. Ollis, G. Schenk, L.R. Gahan, Immobilization of the enzyme GpdQ on magnetite nanoparticles for organophosphate pesticide bioremediation, J. Inorg. Biochem. 131 (2014) 1–7. [56] U. Condomitti, A. Zuin, A.T. Silveira, K. Araki, H.E. Toma, Magnetic nanohydrometallurgy: a promising nanotechnological approach for metal production and recovery using functionalized superparamagnetic nanoparticles, Hydrometallurgy 125 (2012) 148–151. [57] I. Giouroudi, F. Keplinger, Microfluidic biosensing systems using magnetic nanoparticles, Int. J. Mol. Sci. 14 (2013) 18535–18556. [58] F. Fahrni, M.W.J. Prins, L.J. van Ijzendoorn, Magnetization and actuation of polymeric microstructures with magnetic nanoparticles for application in microfluidics, J. Magn. Magn. Mater. 321 (2009) 1843–1850. [59] M. Pumera, J. Wang, E. Grushka, R. Polsky, Gold nanoparticle-enhanced microchip capillary electrophoresis, Anal. Chem. 73 (2001) 5625–5628. [60] M. Pumera, Nanomaterials meet microfluidics, Chem. Commun. 47 (2011) 5671–5680. [61] M. Medina-Sanchez, S. Miserere, A. Merkoci, Nanomaterials and lab-on-a-chip technologies, Lab Chip 12 (2012) 1932–1943.

167

[62] J.N. Tey, I.P.M. Wijaya, J. Wei, I. Rodriguez, S.G. Mhaisalkar, Nanotubes-/nanowiresbased, microfluidic-integrated transistors for detecting biomolecules, Microfluid. Nanofluid. 9 (2010) 1185–1214. [63] M.E. Corman, N. Bereli, S. Ozkara, L. Uzun, A. Denizli, Hydrophobic cryogels for DNA adsorption: effect of embedding of monosize microbeads into cryogel network on their adsorptive performances, Biomed. Chromatogr. 27 (2013) 1524–1531. [64] Y.H. Chen, G. Nurumbetov, R. Chen, N. Ballard, S.A.F. Bon, Multicompartmental Janus microbeads from branched polymers by single-emulsion droplet microfluidics, Langmuir 29 (2013) 12657–12662. [65] S.S. Guo, Y.L. Deng, L.B. Zhao, H.L.W. Chan, X.Z. Zhao, Effect of patterned micromagnets on superparamagnetic beads in microchannels, J. Phys. Appl. Phys. 41 (2008). [66] Y.-H. Lin, A. Das, M.-H. Wu, T.-M. Pan, C.-S. Lai, Microfluidic chip integrated with an electrolyte-insulator-semiconductor sensor for pH and glucose level measurement, Int. J. Electrochem. Sci. 8 (2013) 5886–5901. [67] Y.-H. Lin, S.-H. Wang, M.-H. Wu, T.-M. Pan, C.-S. Lai, J.-D. Luo, C.-C. Chiou, Integrating solid-state sensor and microfluidic devices for glucose, urea and creatinine detection based on enzyme-carrying alginate microbeads, Biosens. Bioelectron. 43 (2013) 328–335. [68] S.-B. Huang, M.-H. Wu, G.-B. Lee, Microfluidic device utilizing pneumatic microvibrators to generate alginate microbeads for microencapsulation of cells, Sensors Actuators B Chem. 147 (2010) 755–764. [69] J. Sheng, L. Zhang, J. Lei, H. Ju, Fabrication of tunable microreactor with enzyme modified magnetic nanoparticles for microfluidic electrochemical detection of glucose, Anal. Chim. Acta. 709 (2012) 41–46. [70] Y. Zheng, S. Zhao, Y.-M. Liu, A magnetically active microfluidic device for chemiluminescence bioassays, Analyst 136 (2011) 2890–2892. [71] Y.-H. Lin, C.-H. Chiang, M.-H. Wu, T.-M. Pan, J.-D. Luo, C.-C. Chiou, Solid-state sensor incorporated in microfluidic chip and magnetic-bead enzyme immobilization approach for creatinine and glucose detection in serum, Appl. Phys. Lett. 99 (2011). [72] S. Agrawal, K. Paknikar, D. Bodas, Development of immunosensor using magnetic nanoparticles and circular microchannels in PDMS, Microelectron. Eng. 115 (2014) 66–69. [73] D. Lombardi, P.S. Dittrich, Droplet microfluidics with magnetic beads: a new tool to investigate drug-protein interactions, Anal. Bioanal. Chem. 399 (2011) 347–352. [74] B. Teste, F. Malloggi, J.-M. Siaugue, A. Varenne, F. Kanoufi, S. Descroix, Microchip integrating magnetic nanoparticles for allergy diagnosis, Lab Chip 11 (2011) 4207–4213. [75] S. Lindsay, T. Vazquez, A. Egatz-Gomez, S. Loyprasert, A.A. Garcia, J. Wang, Discrete microfluidics with electrochemical detection, Analyst 132 (2007) 412–416. [76] S. Park, M. Vosguerichian, Z. Bao, A review of fabrication and applications of carbon nanotube film-based flexible electronics, Nanoscale 5 (2013) 1727–1752. [77] A. Farmany, Carbon nanotubes in chemical analysis, World J. Appl. Scie. 10 (2010) 75–77. [78] M.F.L. De Volder, S.H. Tawfick, R.H. Baughman, A.J. Hart, Carbon nanotubes: present and future commercial applications, Science 339 (2013) 535–539. [79] B. Perez-Lopez, A. Merkoci, Carbon nanotubes and graphene in analytical sciences, Microchim. Acta 179 (2012) 1–16. [80] N. Saifuddin, A.Z. Raziah, A.R. Junizah, Carbon Nanotubes: A Review on Structure and Their Interaction with Proteins, J. Chem. 2013 (2013) (18 pp.). [81] S. Daniel, T.P. Rao, K.S. Rao, S.U. Rani, G.R.K. Naidu, H.-Y. Lee, T. Kawai, A review of DNA functionalized/grafted carbon nanotubes and their characterization, Sensors Actuators B Chem. 122 (2007) 672–682. [82] J. Yu, S.M. Matthews, K. Yunus, J.G. Shapter, A.C. Fisher, Integration of enzyme immobilised single-walled carbon nanotube arrays into microchannels for glucose detection, Int. J. Electrochem. Sci. 8 (2013) 1849–1862. [83] L.W. Bezuidenhout, N. Nazemifard, A.B. Jemere, D.J. Harrison, M.J. Brett, Microchannels filled with diverse micro- and nanostructures fabricated by glancing angle deposition, Lab Chip 11 (2011) 1671–1678. [84] S. Numthuam, T. Kakegawa, T. Anada, A. Khademhosseini, H. Suzuki, J. Fukuda, Synergistic effects of micro/nano modifications on electrodes for microfluidic electrochemical ELISA, Sensors Actuators B Chem. 156 (2011) 637–644. [85] M. Yang, S. Sun, Y. Kostov, A. Rasooly, Lab-on-a-chip for carbon nanotubes based immunoassay detection of Staphylococcal Enterotoxin B (SEB), Lab Chip 10 (2010) 1011–1017. [86] A. Wisitsoraat, P. Sritongkham, C. Karuwan, D. Phokharatkul, T. Maturos, A. Tuantranont, Fast cholesterol detection using flow injection microfluidic device with functionalized carbon nanotubes based electrochemical sensor, Biosens. Bioelectron. 26 (2010) 1514–1520. [87] C.K. Chua, A. Ambrosi, M. Pumera, Graphene based nanomaterials as electrochemical detectors in lab-on-a-chip devices, Electrochem. Commun. 13 (2011) 517–519. [88] Y. Tsujita, K. Maehashi, K. Matsumoto, M. Chikae, S. Torai, Y. Takamura, E. Tamiya, Carbon nanotube amperometric chips with pneumatic micropumps, Jpn. J. Appl. Phys. 47 (2008) 2064–2067. [89] J. Turkevich, P.C. Stevenson, J. Hillier, A study of the nucleation and growth processes in the synthesis of colloidal gold, Faraday Discuss. 55–75 (1951). [90] J.R.G. Navarro, F. Lerouge, C. Cepraga, G. Micouin, A. Favier, D. Chateau, M.-T. Charreyre, P.-H. Lanoë, C. Monnereau, F. Chaput, S. Marotte, Y. Leverrier, J. Marvel, K. Kamada, C. Andraud, P.L. Baldeck, S. Parola, Nanocarriers with ultrahigh chromophore loading for fluorescence bio-imaging and photodynamic therapy, Biomaterials 34 (2013) 8344–8351. [91] S.D. Perrault, W.C.W. Chan, Synthesis and surface modification of highly monodispersed, spherical gold nanoparticles of 50–200 nm, J. Am. Chem. Soc. 131 (2009) 17042–17043.

168

R. Monošík, L. Angnes / Microchemical Journal 119 (2015) 159–168

[92] M. Brust, M. Walker, D. Bethell, D.J. Shiffrin, R. Whyman, Synthesis of thiolderivatised gold nanoparticles in a two-phase liquid–liquid system, Chem. Commun (Cambridge) 7 (1994) 801–802. [93] H. SadAbadi, S. Badilescu, M. Packirisamy, R. Wuethrich, Integration of gold nanoparticles in PDMS microfluidics for lab-on-a-chip plasmonic biosensing of growth hormones, Biosens. Bioelectron. 44 (2013) 77–84. [94] S. Gomez-de Pedro, D. Lopes, S. Miltsov, D. Izquierdo, J. Alonso-Chamarro, M. Puyol, Optical microfluidic system based on ionophore modified gold nanoparticles for the continuous monitoring of mercuric ion, Sensors Actuators B Chem. 194 (2014) 19–26. [95] E. Chung, R. Gao, J. Ko, N. Choi, D.W. Lim, E.K. Lee, S.-I. Chang, J. Choo, Trace analysis of mercury(II) ions using aptamer-modified Au/Ag core-shell nanoparticles and SERS spectroscopy in a microdroplet channel, Lab Chip 13 (2013) 260–266. [96] S.V. Pereira, F.A. Bertolino, G.A. Messina, J. Raba, Microfluidic immunosensor with gold nanoparticle platform for the determination of immunoglobulin G anti-Echinococcus granulosus antibodies, Anal. Biochem. 409 (2011) 98–104. [97] K.H. Cheong, D.K. Yi, J.-G. Lee, J.-M. Park, M.J. Kim, J.B. Edel, C. Ko, Gold nanoparticles for one step DNA extraction and real-time PCR of pathogens in a single chamber, Lab Chip 8 (2008) 810–813. [98] C.X. Luo, Q. Fu, H. Li, L.P. Xu, M.H. Sun, Q. Ouyang, Y. Chen, H. Ji, PDMS microfludic device for optical detection of protein immunoassay using gold nanoparticles, Lab Chip 5 (2005) 726–729. [99] A. Prabhakar, S. Mukherji, A novel C-shaped, gold nanoparticle coated, embedded polymer waveguide for localized surface plasmon resonance based detection, Lab Chip 10 (2010) 3422–3425. [100] W. Chen, T. Li, S. He, D. Liu, Z. Wang, W. Zhang, X. Jiang, Recent progress in the application of microfluidic systems and gold nanoparticles in immunoassays, Sci. China Chem. 54 (2011) 1227–1232. [101] H.S. Wang, F.N. Xiao, Z.Q. Li, J. Ouyang, Z.Q. Wu, X.H. Xia, G.J. Zhou, Sensitive determination of reactive oxygen species in cigarette smoke using microchip

[102]

[103]

[104]

[105]

[106]

[107]

[108]

[109]

[110]

electrophoresis-localized surface plasmon resonance enhanced fluorescence detection, Lab Chip 14 (2014) 1123–1128. H. Zhang, X. Fu, J. Hu, Z. Zhu, Microfluidic bead-based multienzyme-nanoparticle amplification for detection of circulating tumor cells in the blood using quantum dots labels, Anal. Chim. Acta. 779 (2013) 64–71. M.A. Ali, S. Srivastava, P.R. Solanki, V.V. Agrawal, R. John, B.D. Malhotra, Nanostructured anatase-titanium dioxide based platform for application to microfluidics cholesterol biosensor, Appl. Phys. Lett. 101 (2012) 084105. L.C. Taylor, T.B. Kirchner, N.V. Lavrik, M.J. Sepaniak, Surface enhanced Raman spectroscopy for microfluidic pillar arrayed separation chips, Analyst 137 (2012) 1005–1012. A.J. Tavares, M.O. Noor, C.H. Vannoy, W.R. Algar, U.J. Krull, On-chip transduction of nucleic acid hybridization using spatial profiles of immobilized quantum dots and fluorescence resonance energy transfer, Anal. Chem. 84 (2012) 312–319. Y. Luo, W. Sun, C. Liu, G. Wang, N. Fang, Superlocalization of single molecules and nanoparticles in high-fidelity optical imaging microfluidic devices, Anal. Chem. 83 (2011) 5073–5077. E. Jang, W.-G. Koh, Multiplexed enzyme-based bioassay within microfluidic devices using shape-coded hydrogel microparticles, Sensors Actuators B Chem. 143 (2010) 681–688. D.N. Kim, Y. Lee, W.-G. Koh, Fabrication of microfluidic devices incorporating beadbased reaction and microarray-based detection system for enzymatic assay, Sensors Actuators B Chem. 137 (2009) 305–312. D. Choi, E. Jang, J. Park, W.-G. Koh, Development of microfluidic devices incorporating non-spherical hydrogel microparticles for protein-based bioassay, Microfluid. Nanofluid. 5 (2008) 703–710. B.U. Moon, M.G. de Vries, B.H.C. Westerink, E. Verpoorte, Development and characterization of a microfluidic glucose sensing system based on an enzymatic microreactor and chemiluminescence detection, Sci. China-Chem. 55 (2012) 515–523.