Next Article in Journal
Matrix Effects on the Microcystin-LR Fluorescent Immunoassay Based on Optical Biosensor
Previous Article in Journal
Use of Vegetation Health Data for Estimation of Aus Rice Yield in Bangladesh
Previous Article in Special Issue
Metabolic Discrimination of Select List Agents by Monitoring Cellular Responses in a Multianalyte Microphysiometer
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Magnetic Particle-Based Hybrid Platforms for Bioanalytical Sensors

1
School of Materials Engineering, Purdue University, West Lafayette, IN 47907-2045, USA
2
Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, NY 13699-5810, USA
*
Authors to whom correspondence should be addressed.
Sensors 2009, 9(4), 2976-2999; https://doi.org/10.3390/s90402976
Submission received: 19 February 2009 / Revised: 13 April 2009 / Accepted: 23 April 2009 / Published: 23 April 2009
(This article belongs to the Special Issue Toxin Sensors)

Abstract

:
Biomagnetic nano and microparticles platforms have attracted considerable interest in the field of biological sensors due to their interesting physico-chemical properties, high specific surface area, good mechanical stability and opportunities for generating magneto-switchable devices. This review discusses recent advances in the development and characterization of active biomagnetic nanoassemblies, their interaction with biological molecules and their use in bioanalytical sensors.

1. Introduction

In recent years, numerous types of magnetic particles of nanometer and micrometer dimensions and composites of these materials have become key components in different areas like catalysis, environmental remediation, the biomedical field and sensing devices, cell labeling and immunomagnetic separations, magnetic resonance imaging, targeted drug delivery, and bio-imaging [112]. Cell isolation, enzyme immobilization, drug targeting, waste water treatment are just few examples of such applications. These materials offer the potential of enhanced mechanical and catalytic properties when compared to their bulk counterparts. In the biosensors field, they have been used as bioimmobilization platforms, magnetic carriers of biomolecules, to separate or concentrate analytes and to control electrochemical processes at electrode surfaces [2,11,1317]. The combination of magnetic manipulation with bioimmobilization, separation and detection capabilities have created unique opportunities for enhancing the performance of sensing devices.
Of the various magnetic materials reported in the literature for sensing purposes, iron oxides, mainly Fe3O4 have been the most widely used because of their simple preparation and superparamagnetic properties. Iron oxide nanoparticles (NPs) are also biocompatible, displaying no hemolytic activity or genotoxicity. The NPs can either be used for simple adsorption of biomolecules, or functionalized or encapsulated in polymers or silica materials to fabricate hybrid composites with increased biocompatibility and added functionalities. These materials, deposited onto the surface of a glassy carbon (GCE) electrode have provided performance characteristics comparable with those of Prussian Blue modified electrodes [14]. Fe3O4 particles have catalytic active sites for sensing hydrogen peroxide [14,18], which is the product of many enzymatic reactions (e.g. glucose oxidase, lactate dehydrogenase, cholesterol oxidase) and a key component in various chemical, biological, pharmaceutical, clinical, environmental, and food processes. Magnetic iron oxide NPs have gained a great deal of attention also due to their potential for providing control of electrochemical processes [19,20] and creating magneto-switchable devices [14,21]. Biological recognition elements can be attached to their surface to develop various catalytic and affinity sensors. The use of magnetic particles for this purpose brings a number of additional advantages such as control and transport of the bioassembly to a specific location onto/close to the transducer surface. Furthermore, they can be retained and removed with a magnet without affecting the transducer surface, thus creating possibilities for regeneration and reuse.
Extensive research papers and reviews covering the synthesis and characterization of various magnetic particles were published in literature in recent years. In this review, we focus on the most important and widely used magnetic particles-biomolecule hybrid systems for sensing applications, their use as electrode materials and immobilization matrices, and discuss the success and limitations of these materials in biological sensors.

2. Biomagnetic Particles Platforms

Significant progress has been made in the control of size, size distribution, shape, and chemical composition of magnetic particles in recent years [2240]. These are readily available in different forms (Fe2O3, Fe3O4, Fe3S4, MO-Fe2O3 where M = Ni, Co, Zn etc) and can be purchased from several companies or prepared using established synthetic procedures [10]. However, bare magnetic particles tend to easily aggregate and therefore their use for bioanalytical purposes can be difficult. In addition, most of these particles are prepared in hexane or other organic solvents and therefore many biological applications involve particles with modified surfaces that render them biocompatible. For example, they can be surface functionalized with different organic or inorganic coatings in a core-shell format or be prepared in a composite form using various synthetic polymers and natural polysaccharides, like alginate cellulose and dextran [4144], polyaniline [4555], or silica glasses [45,5668]. Tridimensional multilayer films of carbon nanotubes with Fe2O3 introduced in the nanotubes have also been reported for development of a magnetic electrochemical platform for enzyme sensors [69]. This material provided enhanced adsorption of protein molecules, controlled deposition of higher density of carbon nanotubes onto the electrode surface and improved electrochemical properties.
An elegant approach is to coat the particle surface with a gold shell [23,7083], favouring protein binding by taking advantage of their gold affinity. Another interesting example is to coat the NPs with a porous, optically transparent sol-gel layer resulting in a multifunctional hybrid material in which the outer silica shell stabilizes the particles, induces biocompatibility and provides sites for surface modification with biological molecules, electronic mediators or fluorescent labels [84,85]. Such hybrid materials combining the properties of silica microspheres with the advantages of magnetic particles hold promise for additional applications. For example, multifunctional magnetic particles that incorporate chromophores can be easily manipulated through the use of an external magnetic field, while their position at a given time and place can be monitored using fluorescence methods [86,87]. Chromophores used for such applications included organic dyes such as rodhamine [84] as well as quantum dots, featuring narrow emission bandwidth, large two-photon absorption and continuous adsorption spectra [12,8894].
Anker et al. [95] synthesized metal-capped magnetically-modulated nanoprobes (Mag-MOON), that have the capacity to rotate under changing magnetic fields and emit light fluxes in different orientations. In general, fluorescent NPs emit light uniformly in all directions. When coated with a metal layer the symmetry is disturbed and the particles start emitting different amounts of light in different orientations. The orientation of the particle can also be tracked in time. The use of Mag-MOON particles allows in-situ fast background subtraction and provides a significant increase of signal-to-noise ratio. Therefore, immunoassays with a variety of fluorescent labels can be designed. For example, fluorescent dyes have limitations in terms of signal-to-noise ratio when cellular responses are investigated. Mag-MOONs have the potential to increase the sensitivity of these assays when used in nanosensors that are designed to perform rapid single cell measurements. Immunoassays based on Mag-MOONs can be designed for protein detection. Briefly, the Mag-MOONs can be functionalized with molecular recognition elements or antibodies that can bind specifically analytes of interest. In a subsequent step a fluorescent tag is added to increase Mag-MOONs brightness and allow antigen detection (Figure 1).
Silica-coated magnetites were obtained using various synthetic procedures [93,94,96101]. The thickness of the outer silica shell can be tuned by changing the concentration of the silica precursors during synthesis [84]. Zhao et al. [102] fabricated magnetic nanospheres covered with a mesoporous silica shell starting from uniform magnetite NPs, with a mean diameter of 120 nm. These were subsequently covered by a mesoporous silica coating via sol-gel polymerization using tetraetoxysilane (TEOS) and n-octadecyltrimethoxysilane (C18TMS). In the last step, a reduction of the hematite core under an atmosphere of H2 and N2 was performed, to lead to the formation of magnetic core/mesoporous silica shells with a narrow size distribution and a mean diameter of approximately 270 nm.
Lee, et al. [97] recently reported a one-pot synthesis of uniformly sized, non-agglomerated magnetic silica core-shell particles by using a reverse micelles procedure and alkoxide precursors. The synthesis was performed at 90 °C, which allowed maintaining the micelle structure. Two model enzymes (lipase and α-chemotrypsin) were crosslinked with glutaraldehyde (GA) and the results were compared with those obtained by covalent attachment on the NPs surface, through amine functionalization. As an alternative, biological molecules can be entrapped within the silica glass to generate a biologically active material with enhanced stability while providing magnetic properties for easy manipulation and control under a magnetic field. Preparation of silica coated iron oxide NPs with an average diameter of 5 – 7 nm has been described in the literature [96]. The size of the magnetic nanocomposite after the deposition of the silica was ∼ 53 nm.

3. Magnetic Activation of Redox Processes in Bioanalytical Sensors

In bioelectronic devices, such as biosensors and biofuel cells, the electrical contact between enzymes and the electrodes is essential [103114]. The main challenge in achieving good electrical contact stays in the lack of direct communication between the redox (Reduction-Oxidation reaction) center of the biomolecule and the electrode surface. Solutions such as attachment of redox-relay groups to the enzyme, the use of diffusional electron mediators, or the immobilization in a redox polymer matrix have poor efficiency. Problems include the inappropriate orientation of enzyme in respect to the electrode, and conformational modifications of the protein structure. The conjugation of NPs with enzymes in hybrid devices holds promise for the development of novel and improved biosensing platforms and ensures electrical ‘wiring’ between the enzyme and the electrode. Redox-active units are used in a series of electrocatalytical and bioelectrocatalytical processes. Magnetic particles have been functionalized with redox units and subsequently used in reactions relevant for such processes. Examples of redox-active units that have been used to functionalize magnetic nano or micro particles include microperoxidase-11, pyrroloquinoline quinone, 2,3-dichloro-1,4-naphthoquinone, N-ferrocenylmethyl)aminohexanoic acid, or N-methyl-N”-(dodecanoic acid)-4,4′-bipyridinium [115,116]. When redox units-functionalized magnetic particles are attracted to the electrode surface with the help of a magnet placed underneath the electrode, the electrical contact between the redox units on the particles and the electrode is activated and the electrochemical response of the sensor is switched “ON”. In turn, when the magnet is placed on top of the electrode, the NPs are removed from the electrode surface, and the electrochemical response is switched “OFF” [117].
Redox relay units such as bipyridinium or ferrocene are also part of this set-up, and can serve as mediators for electron transfer between redox enzyme and the electrode [115]. This approach has been used for enzymes such as glucose oxidase (GOx) and nitrate reductase [118]. Under a magnetic field, ferrocene oxidizes to ferrocenyl cations. In turn, the ferrocenyl cations have an oxidizing effect on the redox center of the GOx. Removing the magnetic particles from the electrode also removes the electrical contact between the ferrocene and the electrode, inhibiting glucose oxidation. In the case of nitrate oxidase [115], bipyridinium was used as a reducing agent in the reduction process of nitrate to nitrite. When the bipyridinium functionalized magnetic NPs interacted with the electrode under an electrical field (E = − 0.7V), the nitrate-nitrite transformation was favored only when a magnet was positioned in the system in such a way that the NPs were attracted to the electrode. In the same time, the removal of the magnetic particles led to the electrocatalyzed reactions being switched off. Lactate dehydrogenase (LDH) was also used in a similar approach that included pyrroloquinoline quinone as a relay mediator for the activation/deactivation of the NADH-NAD+ transformation [119121]. Selective dual biosensors were also designed with LDH and GOx and magnetic particles functionalized with monolayers of PQQ-NAD+ and ferrocene [122]. These were tested in both oxidation of glucose and inhibition of lactate oxidation when no electrical field was applied. When a small electrical field was applied (potential range: −0.13 < E < 0.13 V), the oxidation of lactate was enabled, while the oxidation of glucose was inhibited, since the potential range used does not favor the oxidation of ferrocene units.

4. Biofunctionalization of Magnetic Nanoparticles

Immobilization of enzymes, antibodies, oligonucleotides, and other biologically active compounds onto magnetic NP platforms is a key element in using these structures for biosensing purposes. Fabricating biofunctionalized magnetic materials containing a high amount of the biological element with high activity and stability is essential for the design of robust sensors that take advantage of the magnetic capabilities. Various routes for the fabrication of biofunctionalized magnetic NPs include traditional methods such as covalent binding, adsoprtion, specific affinity interactions, and entrapment in porous surface layers. In the following sections we describe representative procedures utilized for this purpose and provide selected examples reported in the literature.

4.1. Biofunctionalized Magnetic Nanoparticles Via Covalent Binding

The primary functionalization of iron oxide NPs with organic functionalities is the first step in the covalent binding of biomolecules to their surfaces. The drawbacks of this method stay in the restrictions derived from the biomolecule conformation being imposed by their orientation on the support upon binding. Functionalization of magnetic NPs with carboxyl, amino or hydroxyl groups prior to the covalent binding is traditionally used [6,39,123138]. Hong et al. [139] functionalized magnetic nanogels through a carbodiimide activation procedure. In this case, polyacrylamide (PAM) coated Fe3O4 NPs and Hoffman degradation was used to obtain amino-functionalized magnetic nanogels with a 25 nm diameter. Subsequently, α-chymotrypsin was covalently attached to the nanogel’s surface. The enzymatic activity was largely retained and the reaction temperature and usable pH range were wider after the covalent binding as compared to the free enzyme. In the case of the covalent binding, the enzymatic activity was not dramatically affected by varying the pH between 5.8 and 8.9, while for the free enzyme, the enzymatic activity decreased to less than 50% at pH values between 8 and 8.9. The temperature was varied between 35 and 85 °C and the optimum temperature for the both free and covalently bound enzyme was determined to be at 35 °C, while above this temperature, a decrease in activity was observed in both cases. However, after 60 °C, the free enzyme lost all its activity, while the covalently bound enzyme still retained 60% of its activity. The enzymatic activity was retained after storage at 4 °C for 36 days. The magnetic composite was reusable, with 96.8% of the biological activity being maintained after 12 usage cycles. On the other hand, the affinity between the enzyme and the substrate was lower than that of the free enzyme. An explanation related to sterric effects of diffusion barriers of the substrate to the enzymatic active sites was proposed. More recently [140], the same authors used a hydrophilic polymer with free carboxyl groups to covalently immobilize α-chymotrypsin to the surface of magnetic iron oxide NPs, followed by in-situ polymerization with 1-ethyl-3-(3-dimethylaminepropyl) carbodiimide (EDC) used as a coupling agent. The enzyme retained 80% of its activity at 65 °C, 90% at 25 °C and the full enzymatic activity at 4 °C. The same long term storage stability and reusability as in the case of the amino functionalized nanogels were observed. Other enzymes covalently immobilized on the surface of magnetic NPs include GOx [138] and peroxidase [141,142], as well as cholesterol oxidase, lipase [143], trypsin and chymotrypsin [131,136,137,144150]. Kuroiwa et al. [151] immobilized chitosanase on amylose-coated Fe3O4 NPs. The amylose provided hydroxyl groups on the NPs surface, which were then coupled with the amino groups of chitosanase via covalent binding. Fe3O4-chitosan NPs, exposing free amino groups on their surface were used to bind alcohol dehydrogenase via GA coupling, with about 48% retention of enzymatic activity [151]. The authors demonstrated the recovery of the enzyme by magnetic separation.

4.2. Biofunctionalized Magnetic Nanoparticles via Surface Adsorption

Core-shell NPs functionalized with polymers were investigated as supports for biomolecule immobilization. Mahmood et al. [152] immobilized lipase on magnetic NPs coated with a oleic acid-Pluronic® (L-64) block copolymer. In this work, the copolymer was used to improve stability (i.e. reduce agglomeration). Up to 90% enzymatic activity of lipase was retained for seven cycles. This extended usability was attributed to hydrophobic interactions between the preatreated NPs and the copolymer. Shamim et al. [153] synthesized core-shell iron oxide NPs coated with poly-(N-isopropylacrylamide) (PNIPAM) and used them to adsorb bovine serum albumin (BSA) on their surface. Thiodiglycolic and 4-vinylaniline were used as surfactants. The core-shell NPs were thermosensitive. Above 32 °C, the structure of the poly-(NIPAM) changes from hydrophilic to hydrophobic. Due to this effect, at temperatures above 32 °C, the magnetic NPs shrink, and are able to adsorb a larger amount of bovin serum albumin (BSA). Lowering the temperature below 32 °C resulted in desorption of the protein. It has been shown that the protein adsorption takes place a larger extent through hydrogen bonding, and less through hydrophobic interactions. Peng et al. [154] fabricated Fe3O4 magnetic NPs with 10 nm in diameter through a chemical precipitation method and further used them for physical adsorption of BSA and lysozyme (LSZ) with partial retention of enzymatic activity. Desorption of both BSA and LSZ was also investigated at the isoelectric points of the enzymes. Kausik et al. [155] used Fe3O4 NPs prepared via a co-precipitation method to design a glucose sensor. The NPs dispersed in chitosan formed a film onto an indium-tin oxide (ITO) glass. Dispersion in chitosan helped preventing aggregation, while the NPs facilitated communication with the electrode surface. This biosensor had a rapid response time (5 s), good linearity (10 – 400 mg dL−1), good reproducibility, and high affinity towards glucose. The sensitivity was of 9.3 μA/(mg·dL·cm2) and the sensor was stable for up to eight weeks at 4 °C.

4.3. Entrapment of biomoleules in magnetic composites

Biomolecules can be entrapped within the different polymeric or silica shells used to form hybrid magnetic composites. For example, spherical silica coated Fe3O4 NPs have allowed stable entrapment of horseradish peroxidase (HRP), simultaneously with the formation of the silica layer [96]. This method resulted in biomagnetic catalysts characterized by a long-term stability with temperature up to 85 °C and pH change, as compared to the free enzyme. However, the entrapped enzyme could lose activity due to conformational changes in the silica matrix and also suffers from possible diffusion limitations of the substrate through the silica pores. The same methodology allowed immobilization of an antibody for the development of an immunoassay, for the quantitative determination of gentamicin with a detection limit of 160 ng/mL. More complex systems with entrapped enzymes combining different types of materials were also reported. Such an example is the use of iron oxide NPs with crosslinked enzyme molecules, which were then encapsulated into large pores of mesoporous silica to form a “hierarchically ordered, mesocellular” structure [145]. These nanocomposites were magnetically separable, highly loaded with enzyme, stable under harsh shaking conditions, resistant to different treatment procedures, and reusable.

4.4. Site specific bioimmobilization onto magnetic nanoparticles

Site specific immobilization onto magnetic particles is an attractive strategy for attaching biomolecules because it provides a favorable orientation for biorecognition events while avoiding conformational changes, and offering magnetic control of the entire assembly. As opposed to other methods, this strategy involving attachment at a specific pre-determined position eliminate the diffusion barriers or chemical bond formation that could affect the biological activity and, therefore, a lower detection limit and a fast response time could be expected for sensors fabricated based on this method. Johnson et al. [156] developed a method for immobilization of affinity-tagged dehalogenase on iron/iron oxide core-shell NPs through a biomimetic approach. The authors used cloned dehalogenase (DhlA) fusion proteins, with an affinity for either silica or iron oxide surfaces [157,158]. Three different DhLA recombinant enzymes were expressed and immobilized on the NPs surface. The enzymes were able to specifically bind to either iron oxide or silica. The DhLA enzymes tagged with iron oxide or silica affinity peptides showed a higher rate of adsorption onto the magnetic NPs when compared to the His-tagged protein. In another example, pre-activated iron oxide beads carrying Ni- iminodiacetic acid (IDA) complexes were used to immobilize a genetically-modified acetylcholinesterase (AChE), having engineered an hexa(histidine) tag. The 6His-AChE-Ni-NTA-NPs system was deposited onto the surface of a screen-printed electrode surface with a small magnet placed underneath the electrode. This biosensor was used for the detection of two organophosphorous pesticides, via AChE inhibition [159]. The main advantage of this method for inhibition assays is the very high sensitivity with detection limits of 10−11 M for chlorpyriphos-oxon and the easy reusability of the same electrode. The system could be easily adapted for integration into an autonomously operated magnetoswitchable device for monitoring AChE inhibiting activities.

5. Applications of Biomagnetic Materials in Sensing Technology

5.1. Enzyme Sensors

Enzymatic sensors based on various magnetic platforms, mainly iron oxides were designed with the advantages of offering high enzyme loading and control of the localization of the sensitive material through the use of a magnet allowing for the enzymatic reactions to occur in the close proximity of the transducer surface [159163].
The transducing component is easily renewable and reusable. This is due to the ability to control the charging/discharging of its surface by application of a magnetic field, providing reusability of the same electrode for several analyses. Examples include sensors based on tyrosinase for the detection of phenol [162], yeast (YADH/NAD+) [164] for the detection of ethanol, GOx for glucose [163], and AChE for organophosphorus pesticides [151]. Enzyme-immobilized magnetic beads can be incorporated in a flow injection analysis (FIA) system as described by Kauffmann et al. [161]. Figure 2 shows the schematic diagram of a FIA assay for detection of glucose using glucose oxidase modified magnetic microparticles. Functionalized magnetic particles were injected into the FIA system and retained near the detector using a pair of two small permanent magnets. An amperometric system for the detection of glucose with glucose oxidase immobilized onto the magnetic particles was developed based on this principle. The porous biomagnetic particles were ferromagnetic spinnel type iron oxide (γ-Fe2O3) with the GOx immobilized after silanization with aminopropyltrietoxysilane followed by covalent binding using GA.

5.2. Immunosensors

Magnetic particles functionalized with specific antibodies (Ab) have been used for the design of immunomagnetic sensors through the immobilization of the Ab-NPs assembly on the surface of an electrochemical transducer [3,165167]. For these types of immunosensors, the immunomagnetic complex is magnetically attached to the surface of the screen printed electrode. The utilization of Ab-coated magnetic particles is efficient in overcoming the need of regeneration of the sensing surface and makes possible integration into automatic systems, difficult to achieve otherwise due to the obstacles in renewing the sensing surface. The immunocomplex is usually quantified through the use of enzyme labels, with the electrochemical detection of the enzyme reaction product after the complex is exposed to the enzymatic substrate, or through a fluorescent label followed by fluorescence detection. An example of amperometric immunosensing assay obtained by immobilizing the antibody onto a solid carbon paste electrode using core-shell magnetic NPs is shown in Figure 3 [167].
Different analytes were detected using this method, such as: rabbit IgG [168170], non-pathogenic E. coli O157 [171], polychlorinated biphenyls (PCBs), the herbicide 2,4-D, atrazine [171175] pesticides and bacterial pathogens [176,177]. For example, streptavidin activated magnetic microbeads were used for the immobilization of an antibody for atrazine, a small pesticide molecule, allowing for the determination of its concentration in biological samples, with a detection limit of 0.027 nmol L−1 [173]. In another work, immunomagnetic separation coupled with differential pulse voltammetry allowed detection of Arochlor 1248 PCB mixture with a detection limit of 0.4 ng/mL using screen-printed three electrode strips [178]. Other immunosensors with renewable electrode surface were reported for the detection of pathogens such as Salmonella Typhimurium [176,177]. Another interesting application of immunomagnetic NPs was for selectively concentrating traces of pathogenic bacteria (Staphyloccocus saprophyticus and Staphyloccocus aureus) via IgGs attached onto the particles surface [179]. It was found that these IgG-NPs conjugates can bind selectively to the cell membrane. Detection limits of as low as 3 × 105 cfu/mL were achieved in aqueous solutions. Other specific examples of monodispersed bio-functional magnetic NPs for protein separation and pathogen detection were discussed recently by Gu et al. [180].

5.3. DNA sensors

DNA sensors with single-stranded (ss) oligodeoxynucleotides immobilized on electrode surfaces [181183] via magnetic beads were also fabricated [184190]. A three layer magnetic NPs structure with a gold surface, silica core and magnetic inner layer was functionalized with DNA and used for quantifying hybridization events [189]. It was found that upon hybridization with complementary oligonucleotides, this structure forms aggregates in the same way as Au NPs. In another work, surfactant-modified oligonucleotides were incorporated into the particle organic shell to create a DNA functionalized surface [188]. For example, monodisperse MnFe2O4 magnetic NPs were biofunctionalized with DNA using a combination of alkylphosphonate and ethoxylated fatty alcohols. This method is based on the affinity of alkylphosphonate for metal oxide surfaces. DNA amplification with magnetic primers in combination with electrochemical detection and enzyme labelling was used to develop a genomagnetic assay for detection of food pathogens such as Salmonella spp [190]. The electrode consisted of a graphite epoxy composite and streptavidin modified magnetic beads with immobilized DNA. Loaiza et al. [191] reported a sensitive method for isolation and detection of DNA from bacterial cells using disposable magnetic DNA sensors. Screen-printed gold electrodes with a 4 mm in diameter working electrode surface were used as amperometric transducers in this example.
Figure 4 shows a schematic of the protocol used for enzyme amplification. The magnetic particles were functionalized with streptavidin. A 25-mer capture probe was subsequently attached, followed by the hybridization process. In the next step, streptavidin-peroxidase was attached and the functionalized magnetic particles were attached to the surface of the electrode through a magnet. The sensor was used for the detection of asymmetric DPCR amplified products obtained from E. coli bacterial cultures, with high speed, specificity and sensitivity. Another advantage of this method was elimination of false positive results, a drawback of conventional PCR analysis.

6. Conclusions

In this review, we have summarized the most recent developments in the field of biofunctionalized magnetic particles and their applications in bioanalytical sensors. Research in this field has focused mainly on the challenges of creating hybrid composite materials containing biomolecules, magnetic NPs and other inorganic components, and on the development of strategies that can be used to integrate these materials in functional sensing devices. Research in this direction involves scientific aspects of the preparation, structure and properties of magnetic systems and their functionalization with biological materials. This approach is unique in that it combines the high selectivity and specificity of biological processes with the high surface area and magnetic properties of magnetic particles. These properties have been used to provide control and orientation of the biomolecular recognition elements onto transducer surfaces as well as to enhance the response time, selectivity, sensitivity and stability of the sensor. These hybrid systems are the foundation of new generations of materials that could be used in the construction of biosensors, bioreactors, biofuel cells and in other biotechnological applications. The success of these research efforts is still dependent of the transferability of these materials into real life applications. The rapid developments in the field allowing successful fabrication and testing of various sensors designs based on biomagnetic assemblies illustrate the potential of this approach for further applications.

Acknowledgments

This work was supported by grants NSF-DMR-0804506 and NSF-OISE 0727861.

References

  1. Luo, X.; Morrin, A.; Killard, A.J.; Smyth, M.R. Application of nanoparticles in electrochemical sensors and biosensors. Electroanalysis 2006, 18, 319–326. [Google Scholar]
  2. Khan, R.; Dhayal, M. Electrochemical studies of novel chitosan/TiO2 bioactive electrode for biosensing application. Electrochem. Comm 2008, 10, 263–267. [Google Scholar]
  3. Corti, M.; Lascialfari, A.; Micotti, E.; Castellano, A.; Donativi, M.; Quarta, A.; Cozzoli, P.D.; Manna, L.; Pellegrino, T.; Sangregorio, C. Magnetic properties of novel superparamagnetic MRI contrast agents based on colloidal nanocrystals. J. Magn.Magn. Mater 2008, 320, E320–E323. [Google Scholar]
  4. Jun, Y.W.; Huh, Y.M.; Choi, J.S.; Song, H.T.; Kim, S.; Yoon, S.; Kim, K.S.; Shin, J.S.; Suh, J.S.; Cheon, J. Nanoscale size effect of magnetic nanocrystals and their utilization for cancer diagnosis via magnetic resonance imaging. J. Am. Chem. Soc 2005, 127, 5732–5733. [Google Scholar]
  5. Song, H.T.; Choi, J.S.; Huh, Y.M.; Kim, S.; Jun, Y.W.; Suh, J.S.; Cheon, J. Surface Modulation of Magnetic Nanocrystals in the Development of highly efficient magnetic resonance probes for intracellular labeling. J. Am. Chem. Soc 2005, 127, 9992–9993. [Google Scholar]
  6. Hanessian, S.; Grzyb, J.A.; Cengelli, F.; Juillerat-Jeanneret, L. Synthesis of chemically functionalized superparamagnetic nanoparticles as delivery vectors for chemotherapeutic drugs. Bioorgan. Med. Chem 2008, 16, 2921–2931. [Google Scholar]
  7. Liu, T.Y.; Hu, S.H.; Liu, K.H.; Liu, D.M.; Chen, S.Y. Study on controlled drug permeation of magnetic-sensitive ferrogels: Effect of Fe3O4 and PVA. J. Control. Rel 2008, 126, 228–236. [Google Scholar]
  8. Chen, F.H.; Gao, Q.; Ni, J.Z. The grafting and release behavior of doxorubincin from Fe3O4@SiO2 core–shell structure nanoparticles via an acid cleaving amide bond: the potential for magnetic targeting drug delivery. Nanotechnology 2008, 19, 165103–165111. [Google Scholar]
  9. Wu, S.H.; Lin, Y.S.; Hung, Y.; Chou, Y.H.; Hsu, Y.H.; Chang, C.; Mou, C.Y. Multifunctional mesoporous silica nanoparticles for intracellular labeling and animal magnetic resonance imaging studies. Chembiochem 2008, 9, 53–57. [Google Scholar]
  10. Safarik, I.; Safarikova, M. Magnetic nanoparticles and biosciences. Monatsh. Chem 2002, 133, 737–759. [Google Scholar]
  11. Li, Y.F.; Liu, Z.M.; Liu, Y.Y.; Yang, Y.H.; Shen, G.L.; Yu, R.Q. A mediator-free phenol biosensor based on immobilizing tyrosinase to ZnO nanoparticles. Anal. Biochem 2006, 349, 33–40. [Google Scholar]
  12. Insin, N.; Tracy, J.B.; Lee, H.; Zimmer, J.P.; Westervelt, R.M.; Bawendi, M.G. Incorporation of iron oxide nanoparticles and quantum dots into silica microspheres. ACS Nano 2008, 2, 197–202. [Google Scholar]
  13. Salimi, A.; Hallaj, R.; Soltanian, S.; Mamkhezri, H. Nanomolar detection of hydrogen peroxide on glassy carbon electrode modified with electrodeposited cobalt oxide nanoparticles. Anal. Chim. Acta 2007, 594, 24–31. [Google Scholar]
  14. Hrbac, J.; Halouzka, V.; Zboril, R.; Papadopoulos, K.; Triantis, T. Carbon electrodes modified by nanoscopic iron(III) oxides to assemble chemical sensors for the hydrogen peroxide amperometric detection. Electroanalysis 2007, 19, 1850–1854. [Google Scholar]
  15. Schachl, K.; Alemu, H.; Kalcher, K.; Jezkova, J.; Svancara, I.; Vytras, K. Amperometric determination of hydrogen peroxide with a manganese dioxide-modified carbon paste electrode using flow injection analysis. Analyst 1997, 122, 985–989. [Google Scholar]
  16. Yao, S.; Xu, J.; Wang, Y.; Chen, X.; Xu, Y.; Hu, S. A highly sensitive hydrogen peroxide amperometric sensor based on MnO2 nanoparticles and dihexadecyl hydrogen phosphate composite film. Anal. Chim. Acta 2006, 557, 78–84. [Google Scholar]
  17. Hermanek, M.; Zboril, R.; Medrik, I.; Pechousek, J.; Gregor, C. Catalytic efficiency of iron(III) oxides in decomposition of hydrogen peroxide: competition between the surface area and crystallinity of nanoparticles. J. Am. Chem. Soc 2007, 129, 10929–10936. [Google Scholar]
  18. Sljukic, B.; Banks, C.E.; Compton, R.G. Iron oxide particles are the active sites for hydrogen peroxide sensing at multiwalled carbon nanotube modified electrodes. Nano Lett 2006, 6, 1556–1558. [Google Scholar]
  19. Wang, J.; Scampicchio, M.; Laocharoensuk, R.; Valentini, F.; Gonzalez-Garcia, O.; Burdick, J. Magnetic tuning of the electrochemical reactivity through controlled surface orientation of catalytic nanowires. J. Am. Chem. Soc 2006, 128, 4562–4563. [Google Scholar]
  20. Wang, J.; Musameh, M.; Laocharoensuk, R. Magnetic catalytic nickel particles for on-demand control of electrocatalytic processes. Electrochem. Comm 2005, 7, 652–656. [Google Scholar]
  21. Katz, E.; Willner, I. Magneto-stimulated hydrodynamic control of electrocatalytic and bioelectrocatalytic processes. J. Am. Chem. Soc 2004, 124, 10290–10291. [Google Scholar]
  22. Yin, Y.; Alivisatos, A.P. Colloidal nanocrystal synthesis and the organic−inorganic interface. Nature 2005, 437, 664–670. [Google Scholar]
  23. Park, H.Y.; Schadt, M.J.; Wang, L.; Lim, I.I.S.; Njoaki, P.N.; Kim, S.H.; Jang, M.J.; Luo, J.; Zhong, C.J. Fabrication of magnetic core@shell Fe oxide@Au nanoparticles for interfacial bioactivity and bio-separation. Langmuir 2007, 23, 9050–9056. [Google Scholar]
  24. Toderas, F.; Baia, M.; Maniu, D.; Astilean, S. Tuning the plasmon resonances of gold nanoparticles by controlling their size and shape. J. Optoelectron. Adv. M 2008, 10, 2282–2284. [Google Scholar]
  25. Wei, Y.; Klajn, R.; Pinchuk, A.O.; Grzybowski, B.A. Synthesis, shape control, and optical properties of hybrid Au/Fe3O4 “nanoflowers”. Small 2008, 4, 1635–1639. [Google Scholar]
  26. Hickey, S.G.; Waurisch, C.; Rellinghaus, B.; Eychmuller, A. Size and shape control of colloidally synthesized IV–VI nanoparticulate tin(II) sulfide. J. Am. Chem. Soc 2008, 130, 14978–14980. [Google Scholar]
  27. Piccolo, L.; Valcarcel, A.; Bausach, M.; Thomazeau, C.; Uzio, D.; Berhault, G. Tuning the shape of nanoparticles to control their catalytic properties: selective hydrogenation of 1,3-butadiene on Pd/Al2O3. Phys. Chem. Chem. Phys 2008, 10, 5504–5506. [Google Scholar]
  28. Zhang, Z.; Wong, L.M.; Ong, H.G.; Wang, X.J.; Wang, J.L.; Wang, S.J.; Chen, H.; Wu, T. Self-assembled shape - and orientation- controlled synthesis of nanoscale Cu3Si triangles, squares, and wires. Nano Lett 2008, 8, 3205–3210. [Google Scholar]
  29. Grzelczak, M.; Perez-Juste, J.; Mulvaney, P.; Liz-Marzan, L.M. Shape control in gold nanoparticle synthesis. Chem. Soc. Rev 2008, 37, 1783–1791. [Google Scholar]
  30. Hachisu, T.; Yotsumoto, T.; Sugiyama, A.; Iida, H.; Nakanishi, T.; Asahi, T.; Osaka, T. Effect of growth temperature on the shape and crystallinity of chemically produced Fe-Pt nanoparticles. Chem. Lett 2008, 37, 840–841. [Google Scholar]
  31. Vassilieff, T.; Sutton, A.; Kakkar, A.K. Shape control in silver metal nanoparticle construction using dumb-bell dendrimers. J. Mater. Chem 2008, 18, 4031–4033. [Google Scholar]
  32. Kim, M.H.; Lim, B.; Lee, E.P.; Xia, Y. Polyol synthesis of Cu2O nanoparticles: use of chloride to promote the formation of a cubic morphology. J. Mater. Chem 2008, 18, 4069–4073. [Google Scholar]
  33. Somorjai, G.A.; Park, J.Y. Colloid science of metal nanoparticle catalysts in 2D and 3D structures. challenges of nucleation, growth, composition, particle shape, size control and their influence on activity and selectivity. Top. Catal 2008, 49, 126–135. [Google Scholar]
  34. Hofmann, C.; Rusakova, I.; Ould-Ely, T.; Prieto-Centurion, D.; Hartman, K.B.; Kelly, A.T.; Luttge, A.; Whitmire, K.H. Shape control of new FexO-Fe3O4 and Fe1-yMnyO-Fe3-zMnzO4 nanostructures. Adv. Funct. Mater 2008, 18, 1661–1667. [Google Scholar]
  35. Susut, C.; Nguyen, T.D.; Chapman, G.B.; Tong, Y. Shape and size stability of Pt nanoparticles for MeOH electro-oxidation. Electrochim. Acta 2008, 53, 6135–6142. [Google Scholar]
  36. Chou, N.H.; Ke, X.; Schiffer, P.; Schaak, R.E. Room-temperature chemical synthesis of shape-controlled indium nanoparticles. J. Am. Chem. Soc 2008, 130, 8140–8141. [Google Scholar]
  37. Kilin, D.S.; Prezhdo, O.V.; Xia, Y. Shape - controlled synthesis of silver nanoparticles: Ab initio study of preferential surface coordination with citric acid. Chem. Phys. Lett 2008, 458, 113–116. [Google Scholar]
  38. Scholes, G.D. Controlling the optical properties of inorganic nanoparticles. Adv. Funct. Mater 2008, 18, 1157–1172. [Google Scholar]
  39. Majewski, P.; Thierry, B. Superparamagnetic magnetite (Fe3O4) nanoparticles for bio-applications. Recent Pat. Mater. Sci 2008, 1, 116–127. [Google Scholar]
  40. Burda, C.; Chen, X.B.; Narayanan, R.; El-Sayed, M.A. Chemistry and properties of nanocrystals of different shapes. Chem. Rev 2005, 105, 1025–1102. [Google Scholar]
  41. Taborda, A.; Carvalho, A. Superparamagnetic iron oxide nanoparticles - proton nuclear magnetic resonance dispersion curves. Eur. Phys. J. Appl. Phys 2008, 43, 145–148. [Google Scholar]
  42. Park, J.H.; von Maltzahn, G.; Zhang, L.; Schwartz, M.P.; Ruoslahti, E.; Bhatia, S.N.; Sailor, Michael J. Magnetic iron oxide nanoworms for tumor targeting and imaging. Adv. Mater 2008, 20, 1630–1635. [Google Scholar]
  43. Zhai, Y.; Wang, X.; Wang, X.; Xie, H.; Gu, H. Acute toxicity and irritation of water-based dextran – coated magnetic fluid injected in mice. J. Biomed. Mater. Res. A 2008, 85, 582–587. [Google Scholar]
  44. Wu, C.C.; Lin, L.Y.; Lin, L.C.; Huang, H.C.; Yang, Y.F.; Liu, Y.B.; Tsai, M.C.; Gao, Y.L.; Wang, W.C.; Hung, S.W.; Yang, S.Y.; Horng, H.E.; Yang, H.C.; Tseng, W.Y.I.; Yeh, H.I.; Hsuan, C.F.; Lee, T.L.; Tseng, W.K. Biofunctionalized magnetic nanoparticles for in vitro labeling and in vivo locating specific biomolecules. Appl. Phys. Lett 2008, 92, 142504–142504. [Google Scholar]
  45. Yu, J.H.; Lee, C.W.; Im, S.S.; Lee, J.S. Structure and magnetic properties of SiO2 coated Fe2O3 nanoparticles synthesized by chemical vapor condensation process. Rev. Adv. Mater. Sci 2003, 4, 55–59. [Google Scholar]
  46. Sharma, R.; Malik, R.; Lamba, S.; Annapoorni, S. Metal oxide/polyaniline nanocomposites: cluster size and composition dependent structural and magnetic properties. Bull. Mater. Sci 2008, 31, 409–413. [Google Scholar]
  47. Wang, Z.; Bi, H.; Liu, J.; Sun, T.; Wu, X. Magnetic and microwave absorbing properties of polyaniline / -Fe2O3 nanocomposite. J. Magn. Magn. Mater 2008, 320, 2132–2139. [Google Scholar]
  48. Reddy, K.R.; Lee, K.P.; Iyengar, A.G. Synthesis and characterization of novel conducting composites of Fe3O4 nanoparticles and sulfonated polyanilines. J. Appl. Polym. Sci 2007, 104, 4127–4134. [Google Scholar]
  49. Jacobo, S.E.; Aphesteguy, J.C.; Lopez, A.R.; Schegoleva, N.N.; Kurlyandskaya, G.V. Influence of the preparation procedure on the properties of polyaniline based magnetic composites. Eur. Polym. J 2007, 43, 1333–1346. [Google Scholar]
  50. Zhao, D.L.; Zeng, X.W.; Xia, Q.S.; Tang, J.T. Fe3O4/polyaniline nanoparticles with core-shell structure and their inductive heating property in AC magnetic field. Key Eng. Mater 2007, 334–335, 1189–1192. [Google Scholar]
  51. Zhao, D.L.; Zhang, H.L.; Zeng, X.W.; Xia, Q.S.; Tang, J.T. Inductive heat property of Fe3O4/polymer composite nanoparticles in an ac magnetic field for localized hyperthermia. Biomed. Mater 2006, 1, 198–201. [Google Scholar]
  52. Dallas, P.; Moutis, N.; Devlin, E.; Niarchos, D.; Petridis, D. Characterization, electrical and magnetic properties of polyaniline /maghemite nanocomposites. Nanotechnology 2006, 17, 5019–5026. [Google Scholar]
  53. Long, Y.; Chen, Z.; Duvail, J.L.; Zhang, Z.; Wan, M. Electrical and magnetic properties of polyaniline /Fe3O4 nanostructures. Phys. B 2005, 370, 121–130. [Google Scholar]
  54. Lu, X.; Yu, Y.; Chen, L.; Mao, H.; Gao, H.; Wang, J.; Zhang, W.; Wei, Y. Aniline dimer-COOH assisted preparation of well - dispersed polyaniline - Fe3O4 nanoparticles. Nanotechnology 2005, 16, 1660–1665. [Google Scholar]
  55. Sharma, R.; Lamba, S.; Annapoorni, S.; Sharma, P.; Inoue, A. Composition dependent magnetic properties of iron oxide - polyaniline nanoclusters. J. Appl. Phys 2005, 97, 014311–014311. [Google Scholar]
  56. Lin, H.A.; Liu, C.H.; Huang, W.C.; Liou, S.C.; Chu, M.W.; Chen, C.H.; Lee, J.F.; Yang, C.M. Novel magnetically separable mesoporous Fe2O3@SBA-15 nanocomposite with fully open mesochannels for protein immobilization. Chem. Mater 2008, 20, 6617–6622. [Google Scholar]
  57. Souza, D.M.; Andrade, A.L.; Fabris, J.D.; Valerio, P.; Goes, A.M.; Leite, M.F.; Domingues, R.Z. Synthesis and in vitro evaluation of toxicity of silica -coated magnetite nanoparticles. J. Non-Cryst. Solids 2008, 354, 4894–4897. [Google Scholar]
  58. Zhang, F.; Wang, C.C. Fabrication of one-dimensional iron oxide / silica nanostructures with high magnetic sensitivity by dipole-directed self-assembly. J. Phys. Chem. C 2008, 112, 15151–15156. [Google Scholar]
  59. Lien, Y.H.; Wu, T.M. Preparation and characterization of thermosensitive polymers grafted onto silica -coated iron oxide nanoparticles. J. Colloid Interface Sci 2008, 326, 517–521. [Google Scholar]
  60. Gu, R.; Gong, X.; Jiang, W.; Hao, L.; Xuan, S.; Zhang, Z. Synthesis and rheological investigation of a magnetic fluid using olivary silica -coated iron particles as a precursor. J. Magn. Magn. Mater 2008, 320, 2788–2791. [Google Scholar]
  61. Hu, S.H.; Chen, S.Y.; Liu, D.M.; Hsiao, C.S. Core/single-crystal-shell nanospheres for controlled drug release via a magnetically triggered rupturing mechanism. Adv. Mater 2008, 20, 2690–2695. [Google Scholar]
  62. Li, L.; Choo, E.S.G.; Liu, Z.; Ding, J.; Xue, J. Double-layer silica core-shell nanospheres with superparamagnetic and fluorescent functionalities. Chem. Phys. Lett 2008, 461, 114–117. [Google Scholar]
  63. Heitsch, A.T.; Smith, D.K.; Patel, R.N.; Ress, D.; Korgel, B.A. Multifunctional particles: Magnetic nanocrystals and gold nanorods coated with fluorescent dye-doped silica shells. J. Solid State Chem 2008, 181, 1590–1599. [Google Scholar]
  64. Xu, Q.; Bian, X.J.; Li, L.L.; Hu, X.Y.; Sun, M.; Chen, D.; Wang, Y. Myoglobin immobilized on Fe3O4@SiO2 magnetic nanoparticles: Direct electron transfer, enhanced thermostability and electroactivity. Electrochem. Comm 2008, 10, 995–999. [Google Scholar]
  65. Shukoor, M.I.; Natalio, F.; Therese, H.A.; Tahir, M.N.; Ksenofontov, V.; Panthoefer, M.; Eberhardt, M.; Theato, P.; Schroeder, H.C.; Mueller, W.E.G.; Tremel, W. Fabrication of a silica coating on magnetic γ-Fe2O3 nanoparticles by an immobilized enzyme. Chem. Mater 2008, 20, 3567–3573. [Google Scholar]
  66. Wang, S.; Cao, H.; Gu, F.; Li, C.; Huang, G. Synthesis and magnetic properties of iron / silica core/shell nanostructures. J. Alloy. Compd 2008, 457, 560–564. [Google Scholar]
  67. Zhang, M.; Cushing, B.L.; O’Connor, C.J. Synthesis and characterization of monodisperse ultra-thin silica-coated magnetic nanoparticles. Nanotechnology 2008, 19, 085601–085601. [Google Scholar]
  68. Lei, Z.; Li, Y.; Wei, X. A facile two-step modifying process for preparation of poly(SStNa)-grafted Fe3O4/SiO2 particles. J. Solid State Chem 2008, 181, 480–486. [Google Scholar]
  69. Song, Q.; Fei, H.; Gang, C.; Shaoning, Y.; Jilie, K. Magnetic assembled electrochemical platform using Fe2O3 filled carbon nanotubes and enzyme. Electrochem. Comm 2007, 9, 2812–2816. [Google Scholar]
  70. Gorin, D.A.; Portnov, S.A.; Inozemtseva, O.A.; Luklinska, Z.; Yashchenok, A.M.; Pavlov, A.M.; Skirtach, A.G.; Moehwald, H.; Sukhorukov, G.B. Magnetic / gold nanoparticle functionalized biocompatible microcapsules with sensitivity to laser irradiation. Phys. Chem. Chem. Phys 2008, 10, 6899–6905. [Google Scholar]
  71. Wang, L.; Park, H.Y.; Lim, S.I.I.; Schadt, M.J.; Mott, D.; Luo, J.; Wang, X.; Zhong, C.J. Core@shell nanomaterials: gold-coated magnetic oxide nanoparticles. J. Mater. Chem 2008, 18, 2629–2635. [Google Scholar]
  72. Gole, A.; Stone, J.W.; Gemmill, W.R.; zur Loye, H.C.; Murphy, C.J. Iron oxide coated gold nanorods: synthesis, characterization, and magnetic manipulation. Langmuir 2008, 24, 6232–6237. [Google Scholar]
  73. Hien, P.; Thao, T.; Cao, C.; Sim, S.J. Application of citrate-stabilized gold-coated ferric oxide composite nanoparticles for biological separations. J. Magn. Magn. Mater 2008, 320, 2049–2055. [Google Scholar]
  74. Tang, D.; Yuan, R.; Chai, Y. Magneto-controlled bioelectronics for the antigen-antibody interaction based on magnetic-core/ gold-shell nanoparticles functionalized biomimetic interface. Bioproc. Biosyst. Eng 2008, 31, 55–61. [Google Scholar]
  75. Bao, J.; Chen, W.; Liu, T.; Zhu, Y.; Jin, P.; Wang, L.; Liu, J.; Wei, Y.; Li, Y. Bifunctional Au-Fe3O4 Nanoparticles for Protein Separation. ACS Nano 2007, 1, 293–298. [Google Scholar]
  76. Kouassi, G.K.; Wang, P.; Sreevatan, S.; Irudayaraj, J. Aptamer-mediated magnetic and gold-coated magnetic nanoparticles as detection assay for prion protein assessment. Biotechnol. Progr 2007, 23, 1239–1244. [Google Scholar]
  77. Xu, Z.; Hou, Y.; Sun, S. Magnetic core/shell Fe3O4/Au and Fe3O4/Au/Ag nanoparticles with tunable plasmonic properties. J. Am. Chem. Soc 2007, 129, 8698–8699. [Google Scholar]
  78. Lo, C.K.; Xiao, D.; Choi, M.M.F. Homocysteine-protected gold-coated magnetic nanoparticles: synthesis and characterization. J. Mater. Chem 2007, 17, 2418–2427. [Google Scholar]
  79. Lu, Q.H.; Yao, K.L.; Xi, D.; Liu, Z.L.; Luo, X.P.; Ning, Q. A magnetic separation study on synthesis of magnetic Fe oxide core/Au shell nanoparticles. Nanoscience 2006, 11, 241–248. [Google Scholar]
  80. Kim, S.H.; Kim, M.J.; Choa, Y.H. Fabrication and estimation of Au-coated Fe3O4 nanocomposite powders for the separation and purification of biomolecules. Mater. Sci. Eng. A 2007, A449–A451, 386–388. [Google Scholar]
  81. Sun, Q.; Reddy, B.V.; Marquez, M.; Jena, P.; Gonzalez, C.; Wang, Q. Theoretical study on gold-coated iron oxide nanostructure: Magnetism and bioselectivity for amino acids. J. Phys. Chem. C 2007, 111, 4159–4163. [Google Scholar]
  82. Seino, S.; Kusunose, T.; Sekino, T.; Kinoshita, T.; Nakagawa, T.; Kakimi, Y.; Kawabe, Y.; Iida, J.; Yamamoto, T.A.; Mizukoshi, Y. Synthesis of gold / magnetic iron oxide composite nanoparticles for biomedical applications with good dispersibility. J. Appl. Phys 2006, 99, 08H101–08H101. [Google Scholar]
  83. Yu, H.; Chen, M.; Rice, P.M.; Wang, S.X.; White, R.L.; Sun, S. Dumbbell-like bifunctional Au-Fe3O4 nanoparticles. Nano Lett 2005, 5, 379–382. [Google Scholar]
  84. Chang, Q.; Zhu, L.; Yu, C.; Tang, H. Synthesis and properties of magnetic and luminescent Fe3O4/SiO2/Dye/SiO2 nanoparticles. J. Lumin 2008, 128, 1890–1895. [Google Scholar]
  85. Qiu, J.; Peng, H.; Liang, R. Ferrocene modified Fe3O4@SiO2 magnetic nanoparticles as building blocks for construction of reagentless enzyme-based biosensors. Electrochem. Comm 2007, 9, 2734–2738. [Google Scholar]
  86. Yoon, T.J.; Kim, J.S.; Kim, B.G.; Yu, K.N.; Cho, M.H.; Lee, J.K. Multifunctional nanoparticles possessing a “Magnetic motor effect” for drug or gene delivery. Angew. Chem. Int. Ed 2005, 44, 1068–1071. [Google Scholar]
  87. Qiu, G.M.; Xu, Y.Y.; Zhu, B.K.; Qiu, G.L. Novel, fluorescent, magnetic, polysaccharide-based microsphere for orientation, tracing, and anticoagulation: preparation and characterization. Biomacromolecules 2005, 6, 1041–1047. [Google Scholar]
  88. Teng, X.; Yang, H. Effects of surfactants and synthetic conditions on the sizes and self-assembly of monodisperse iron oxide nanoparticles. J. Mater. Chem 2004, 14, 774–779. [Google Scholar]
  89. Gaponik, N.; Radtchenko, I.L.; Sukhorukov, G.B.; Rogach, A.L. Luminescent polymer microcapsules addressable by a magnetic field. Langmuir 2004, 20, 1449–1452. [Google Scholar]
  90. Zhu, Y.; Hong, D.; Yang, X.; Hu, Y. Preparation and characterization of core-shell monodispersed agnetic silica microspheres. Colloids Surf. A 2003, 231, 123–129. [Google Scholar]
  91. Claesson, E.M.; Philipse, A.P. Monodisperse magnetizable composite silica spheres with tunable dipolar interactions. Langmuir 2005, 21, 9412–9419. [Google Scholar]
  92. Yang, C.; Guan, Y.; Xing, J.; Liu, J.; Shan, G.; An, Z.; Liu, H. Preparation of magnetic polystyrene microspheres with a narrow size distribution. AIChE J 2005, 51, 2011–2015. [Google Scholar]
  93. Isher, B.R.; Eisler, H.J.; Stott, N.E.; Bawendi, M.G. Emission intensity dependence and single-exponential behavior in single colloidal quantum dot fluorescence lifetimes. J. Phys. Chem. B 2004, 108, 143–148. [Google Scholar]
  94. ankhurst, Q.A.; Connolly, J.; Jones, S.K.; Dobson, J. Applications of magnetic nanoparticles in biomedicine. J. Phys. D: Appl. Phys 2003, 36, R167–R181. [Google Scholar]
  95. nker, J.N.; Kopelman, R. Magnetically modulated optical nanoprobes. Appl. Phys. Lett 2003, 82, 1102–1104. [Google Scholar]
  96. ang, H.H.; Zhang, S.Q.; Chen, X.L.; Zhuang, Z. X; Xu, J.G.; Wang, X.R. Magnetite-containing spherical silica nanoparticles for biocatalysis and bioseparations. Anal. Chem 2004, 76, 1316–1321. [Google Scholar]
  97. Lee, J.; Lee, Y.; Youn, J.K.; Na, H.B.; Yu, T.; Kim, H.; Lee, S.M.; Koo, Y.M.; Kwak, J.H.; Park, H.G.; Chang, H.N.; Hwang, M.; Park, J.G.; Kim, J.; Hyeon, T. Simple synthesis of functionalized superparamagnetic magnetite/silica core/shell nanoparticles and their application as magnetically separable high-performance biocatalysts. Small 2008, 4, 143–152. [Google Scholar]
  98. Lee, D.C.; Mikulec, F.V.; Pelaez, J.M.; Koo, B.; Korgel, B.A. Synthesis and magnetic properties of silica-coated FePt nanocrystals. J. Phys. Chem. B 2006, 110, 11160–11166. [Google Scholar]
  99. Lee, I.S.; Lee, N.; Park, J.; Kim, B.H.; Yi, Y.W.; Kim, T.; Kim, T.K.; Lee, I.H.; Paik, S.R.; Hyeon, T. Ni/NiO core/shell nanoparticles for selective binding and magnetic separation of histidine-tagged proteins. J. Am. Chem. Soc . 2006, 128, 10658–10659. [Google Scholar]
  100. Yi, D.K.; Lee, S.S.; Papaefthymiou, G.C.; Ying, J.Y. Nanoparticle architectures templated by SiO2/Fe2O3 nanocomposites. Chem. Mater 2006, 18, 614–619. [Google Scholar]
  101. Yi, D.K.; Selvan, S.T.; Lee, S.S.; Papaefthymiou, G.C.; Kundaliya, D.; Ying, J.Y. Silica-coated nanocomposites of magnetic nanoparticles and quantum dots. J. Am. Chem. Soc 2005, 127, 4990–4991. [Google Scholar]
  102. Zhao, W.; Gu, J.; Zhang, L.; Chen, H.; Shi, J. Fabrication of uniform magnetic nanocomposite spheres with a magnetic core/mesoporous silica shell structure. J. Am. Chem. Soc 2005, 127, 8916–8917. [Google Scholar]
  103. Trindade, T.; O'Brien, P.; Pickett, N.L. Nanocrystalline semiconductors: Synthesis, properties, and perspectives. Chem. Mater 2001, 13, 3843–3858. [Google Scholar]
  104. Lue, J.T. A review of characterization and physical property studies of metallic nanoparticles. J. Phys. Chem. Solids 2001, 62, 1599–1612. [Google Scholar]
  105. Grieve, K.; Mulvaney, P.; Grieser, F. Synthesis and electronic properties of semiconductor nanoparticles/quantum dots. Curr. Opin. Colloid Interface Sci 2000, 5, 168–172. [Google Scholar]
  106. Schwerdtfeger, P. Gold goes nano- from small clusters to low-dimensional assemblies. Angew. Chem. Int. Ed 2003, 42, 1892–1895. [Google Scholar]
  107. Brust, M.; Kiely, C.J. Some recent advances in nanostructure preparation from gold and silver particles: a short topical review. Colloids Surf. A 2002, 202, 175–186. [Google Scholar]
  108. McConnell, W.P.; Novak, J.P.; Brousseau, L.C., III; Fuierer, R.R.; Tenent, R.C.; Feldheim, D.L. Electronic and optical properties of chemically modified metal nanoparticles and molecularly bridged nanoparticle arrays. J. Phys. Chem. B 2000, 104, 8925–8930. [Google Scholar]
  109. Gangopadhyay, R.; De, A. Conducting polymer nanocomposites: A brief overview. Chem. Mater 2000, 12, 608–622. [Google Scholar]
  110. Katz, E.; Shipway, A.N.; Willner, I. Nanoparticles-From Theory to Applications; Schmid, G., Ed.; Wiley-VCH: Weinheim, Germany, 2003; pp. 368–421. [Google Scholar]
  111. Niemeyer, C.M. Nanoparticles, proteins, and nucleic acids: Biotechnology meets materials science. Angew. Chem. Int. Ed 2001, 40, 4128–4158. [Google Scholar]
  112. Niemeyer, C.M. Functional hybrid devices of proteins and inorganic nanoparticles. Angew. Chem. Int. Ed 2003, 42, 5796–5800. [Google Scholar]
  113. Parak, W.J.; Gerion, D.; Pellegrino, T.; Zanchet, D.; Micheel, C.; Williams, S.C.; Boudreau, R.; Le Gros, M.A.; Larabell, C.A.; Alivisatos, A.P. Biological applications of colloidal nanocrystals. Nanotechnology 2003, 14, R15–R27. [Google Scholar]
  114. Csaki, A.; Maubach, G.; Born, D.; Reichert, J.; Fritzsche, W. DNA-based molecular nanotechnology. Single Molecules 2002, 3, 275–280. [Google Scholar]
  115. Hirsch, R.; Katz, E.; Willner, I. Magneto-Switchable Bioelectrocatalysis. J. Am. Chem. Soc 2000, 122, 12053–12054. [Google Scholar]
  116. Urban, M.; Moller, R.; Fritzsche, W. A paralleled readout system for an electrical DNA-hybridization assay based on a microstructured electrode array. Rev. Sci. Instrum 2003, 74, 1077–1081. [Google Scholar]
  117. Katz, E.; Willner, I. Nanobiotechnology: integrated nanoparticle-biomolecule hybrid systems: Synthesis, properties, and applications. Angew. Chem. Int. Ed 2004, 43, 6042–6108. [Google Scholar]
  118. Bartlett, P.N.; Tebbutt, P.; Whitaker, R.G. Kinetic aspects of the use of modified electrodes and mediators in bioelectrochemistry. Prog. React. Kinet 1991, 16, 55–155. [Google Scholar]
  119. Bardea, A.; Katz, E.; Bueckmann, A.F.; Willner, I. NAD+-dependent enzyme electrodes: Electrical contact of cofactor-dependent enzymes and electrodes. J. Am. Chem. Soc 1997, 119, 9114–9119. [Google Scholar]
  120. Zayats, M.; Katz, E.; Willner, I. Electrical contacting of flavoenzymes and NAD(P)+-dependent enzymes by reconstitution and affinity interactions on phenylboronic acid monolayers associated with Au-electrodes. J. Am. Chem. Soc 2002, 124, 14724–14735. [Google Scholar]
  121. Buckmann, A.F.; Wray, V.; Stocker, A. Synthesis of N6-(2-aminoethyl)-FAD, N6-(6-carboxyhexyl)-FAD, and related compounds. Methods Enzymol 1997, 280, 360–374. [Google Scholar]
  122. Katz, E.; Sheeney-Haj-Ichia, L.; Buckmann, A.F.; Willner, I. Dual biosensing by magneto-controlled bioelectrocatalysis. Angew. Chem. Int. Ed 2002, 41, 1343–1346. [Google Scholar]
  123. Georgelin, T.; Moreau, B.; Bar, N.; Villemin, D.; Cabuil, V.; Horner, O. Functionalization of Fe2O3 nanoparticles through the grafting of an organophosphorous ligand. Sens. Actuat. B 2008, 134, 451–454. [Google Scholar]
  124. Yong, Y.; Bai, Y.; Li, Y.; Lin, L.; Cui, Y.; Xia, C. Preparation and application of polymer-grafted magnetic nanoparticles for lipase immobilization. J. Magn. Magn. Mater 2008, 320, 2350–2355. [Google Scholar]
  125. Li, G.Y.; Huang, K.L.; Jiang, Y.R.; Yang, D.L.; Ding, P. Preparation and characterization of Saccharomyces cerevisiae alcohol dehydrogenase immobilized on magnetic nanoparticles. Int. J. Biol. Macromol 2008, 42, 405–412. [Google Scholar]
  126. Yu, C.C.; Lin, P.C.; Lin, C.C. Site-specific immobilization of CMP-sialic acid synthetase on magnetic nanoparticles and its use in the synthesis of CMP-sialic acid. Chem. Commun 2008, 11, 1308–1310. [Google Scholar]
  127. Fu, X.H. Magnetic-controlled non-competitive enzyme-linked voltammetric immunoassay for carcinoembryonic antigen. Biochem. Eng. J 2008, 39, 267–275. [Google Scholar]
  128. Hung, C.W.; Holoman, T.R.P.; Kofinas, P.; Bentley, W.E. Towards oriented assembly of proteins onto magnetic nanoparticles. Biochem. Eng. J 2008, 38, 164–170. [Google Scholar]
  129. Liu, J.; Lin, S.; Qi, D.; Deng, C.; Yang, P.; Zhang, X. On-chip enzymatic microreactor using trypsin-immobilized superparamagnetic nanoparticles for highly efficient proteolysis. J. Chromatogr. A 2007, 1176, 169–177. [Google Scholar]
  130. Shukoor, M.I.; Natalio, F.; Tahir, M.N.; Ksenofontov, V.; Therese, H.A.; Theato, P.; Schroeder, H.C.; Mueller, W.E.G.; Tremel, W. Superparamagnetic-Fe2O3 nanoparticles with tailored functionality for protein separation. Chem. Commun 2007, 44, 4677–4679. [Google Scholar]
  131. Li, Y.; Yan, B.; Deng, C.; Yu, W.; Xu, X.; Yang, P.; Zhang, X. Efficient on-chip proteolysis system based on functionalized magnetic silica microspheres. Proteomics 2007, 7, 2330–2339. [Google Scholar]
  132. Liang, Y.Y.; Zhang, L.M.; Li, W.; Chen, R.F. Polysaccharide-modified iron oxide nanoparticles as an effective magnetic affinity adsorbent for bovine serum albumin. Colloid Polym. Sci 2007, 285, 1193–1199. [Google Scholar]
  133. Kim, M.J.; An, G.H.; Choa, Y.H. Functionalization of magnetite nanoparticles for protein immobilization. Diffus. Defect Data, Pt. B 2007, 124–126, 895–898. [Google Scholar]
  134. Liang, Y.Y.; Zhang, L.M. Bioconjugation of papain on superparamagnetic nanoparticles decorated with carboxymethylated chitosan. Biomacromolecules 2007, 8, 1480–1486. [Google Scholar]
  135. Lang, C.; Schueler, D.; Faivre, D. Synthesis of magnetite nanoparticles for bio- and nanotechnology: genetic engineering and biomimetics of bacterial magnetosomes. Macromol. Biosci 2007, 7, 144–151. [Google Scholar]
  136. Hong, J.; Gong, P.J.; Yu, J.H.; Xu, D.M.; Sun, H.W.; Yao, S. Conjugation of chymotrypsin on a polymeric hydrophilic nanolayer covering magnetic nanoparticles. J. Mol. Catal. B: Enzym 2006, 42, 99–105. [Google Scholar]
  137. Bilkova, Z.; Slovakova, M.; Minc, N.; Futterer, C.; Cecal, R.; Horak, D.; Benes, M.; le Potier, I.; Krenkova, J.; Przybylski, M.; Viovy, J.L. Functionalized magnetic micro- and nanoparticles: optimization and application to chip tryptic digestion. Electrophoresis 2006, 27, 1811–1824. [Google Scholar]
  138. Rossi, L.M.; Quach, A.D.; Rosenzweig, Z. Glucose oxidase- magnetite nanoparticle bioconjugate for glucose sensing. Anal. Bioanal.Chem 2004, 380, 606–613. [Google Scholar]
  139. Hong, J.; Gong, P.; Xu, D.; Dong, L.; Yao, S. Stabilization of chymotrypsin by covalent immobilization on amine-functionalized superparamagnetic nanogel. J. Biotechnol. 2007, 128, 597–605. [Google Scholar]
  140. Hong, J.; Xu, D.; Gong, P.; Yu, J.; Ma, H.; Yao, S. Covalent-bonded immobilization of enzyme on hydrophilic polymer covering magnetic nanogels. Microporous Mesoporous Mater 2008, 109, 470–477. [Google Scholar]
  141. Wei, C.; Yang, M.; Hu, J.; Li, Q. Electrocatalysis of horseradish peroxidase immobilized on cobalt nanoparticles modified ITO electrode. Anal. Lett 2007, 40, 3182–3194. [Google Scholar]
  142. Sharma, A.; Qiang, Y.; Antony, J.; Meyer, D.; Kornacki, P.; Paszczynski, A. Dramatic increase in stability and longevity of enzymes attached to monodispersive iron nanoparticles. IEEE Trans. Magn 2007, 43, 2418–2420. [Google Scholar]
  143. Dyal, A.; Loos, K.; Noto, M.; Chang, S.W.; Spagnoli, C.; Shafi, K.V.P.M.; Ulman, A.; Cowman, M.; Gross, R.A. Activity of candida rugosa lipase immobilized on gamma-Fe2O3 magnetic nanoparticles. J. Am. Chem. Soc 2003, 125, 1684–1685. [Google Scholar]
  144. Wang, T.H.; Lee, W.C. Immobilization of proteins on magnetic nanoparticles. Biotechnol. Bioprocess Eng 2003, 8, 263–267. [Google Scholar]
  145. Kim, J.; Lee, J.; Na, H.B.; Kim, B.C.; Youn, J.K.; Kwak, J.H.; Moon, K.; Lee, E.; Kim, J.; Park, J.; Dohnalkova, A.; Park, H.G.; Gu, M.B.; Chang, H.N.; Grate, J.W.; Hyeon, T. A magnetically separable, highly stable enzyme system based on nanocomposites of enzymes and magnetic nanoparticles shipped in hierarchically ordered, mesocellular, mesoporous silica. Small 2005, 1, 1203–1207. [Google Scholar]
  146. Li, Y.; Xu, X.; Deng, C.; Yang, P.; Zhang, X. Immobilization of trypsin on superparamagnetic nanoparticles for rapid and effective proteolysis. J. Proteome. Res 2007, 6, 3849–3855. [Google Scholar]
  147. Jeng, J.; Lin, M.F.; Cheng, F.Y.; Yeh, C.S.; Shiea, J. Using high-concentration trypsin-immobilized magnetic nanoparticles for rapid in situ protein digestion at elevated temperature. Rapid Commun. Mass Spectrom 2007, 21, 3060–3068. [Google Scholar]
  148. Hong, J.; Xu, D.; Gong, P.; Sun, H.; Dong, L.; Yao, S. Covalent binding of chymotrypsin on the magnetic nanogels covered by amino groups. J. Mol. Catal. B: Enzym . 2007, 45, 84–90. [Google Scholar]
  149. Zavisova, V.; Koneracka, M.; Tomasovicova, N.; Kopcansky, P.; Timko, M. Some immobilization modes of biologically active substances to fine magnetic particles. Z. Phys. Chem 2006, 220, 241–250. [Google Scholar]
  150. Liu, Z.; Wang, J.; Xie, D.; Chen, G. Polyaniline-coated Fe3O4 nanoparticle-carbon-nanotube composite and its application in electrochemical biosensing. Small 2008, 4, 462–466. [Google Scholar]
  151. Kuroiwa, T.; Noguchi, Y.; Nakajima, M.; Sato, S.; Mukataka, S.; Ichikawa, S. Production of chitosan oligosaccharides using chitosanase immobilized on amylose-coated magnetic nanoparticles. Process Biochem 2008, 43, 62–69. [Google Scholar]
  152. Mahmood, I.; Guo, C.; Xia, H.; Ma, J.; Jiang, Y.; Liu, H. Lipase Immobilization on oleic acid-pluronic (L-64) block copolymer coated magnetic nanoparticles, for hydrolysis at the oil/water interface. Ind. Eng. Chem. Res 2008, 47, 6379–6385. [Google Scholar]
  153. Shamim, N.; Hong, L.; Hidajat, K.; Uddin, M.S. Thermosensitive polymer coated nanomagnetic particles for separation of bio-molecules. Sep. Purif. Technol 2007, 53, 164–170. [Google Scholar]
  154. Peng, Z.G.; Hidajat, K.; Uddin, M.S. Selective and sequential adsorption of bovine serum albumin and lysozyme from a binary mixture on nanosized magnetic particles. J. Colloid Interface Sci 2005, 281, 11–17. [Google Scholar]
  155. Kaushik, A.; Khan, R.; Solanki, P.R.; Pandey, P.; Alam, J.; Ahmad, S.; Malhotra, B.D. Iron oxide nanoparticles–chitosan composite based glucose biosensor. Biosens. Bioelectron 2008, 24, 676–683. [Google Scholar]
  156. Johnson, A.K.; Zawadzka, A.M.; Deobald, L.A.; Crawford, R.L.; Paszczynski, A.J. Novel method for immobilization of enzymes to magnetic nanoparticles. J. Nanopart. Res 2008, 10, 1009–1025. [Google Scholar]
  157. Naik, R.R.; Brott, L.L.; Clarson, S.J.; Stone, M.O. Silica-precipitating peptides isolated from a combinatorial phage display peptide library. J. NanoSci. Nanotechno 2002, 2, 95–100. [Google Scholar]
  158. Brown, S. Engineered iron oxide-adhesion mutants of the Escherichia coli phage lambda receptor. Proc. Nat. Acad. Sci. USA 1992, 89, 8651–8655. [Google Scholar]
  159. Istamboulie, G.; Andreescu, S.; Marty, J.L.; Noguer, T. Highly sensitive detection of organophosphorus insecticides using magnetic microbeads and genetically engineered acetylcholinesterase. Biosens. Bioelectron 2007, 23, 506–512. [Google Scholar]
  160. Elyacoubia, A.; Zayeda, S.I.M.; Blankert, B.; Kauffmann, J.M. Development of an amperometric enzymatic biosensor based on gold modified magnetic nanoporous microparticles. Electroanalysis 2006, 18, 345–350. [Google Scholar]
  161. Nomura, A.; Mehdi, S.S.O.; Kauffmann, J.M. Preparation, Characterization, and application of an enzyme-immobilized magnetic microreactor for flow injection analysis. Anal. Chem 2004, 76, 5498–5502. [Google Scholar]
  162. Liu, Z.; Liu, Y.; Yang, H.; Yang, Y.; Shen, G.; Yu, R. A phenol biosensor based on immobilizing tyrosinase to modified core-shell magnetic nanoparticles supported at a carbon paste electrode. Anal. Chim. Acta 2005, 533, 3–9. [Google Scholar]
  163. Rossi, L.M.; Quach, A.D.; Rosenzweig, Z. Glucose oxidase–magnetite nanoparticle bioconjugate for glucose sensing. Anal. Bioanal.Chem 2004, 380, 606–613. [Google Scholar]
  164. Ivanova, V.; Hristov, J.; Dobreva, E.; Al-Hassan, Z.; Penchev, I. Performance of a magnetically stabilized bed reactor with immobilized yeast cells. Appl. Biochem. Biotechnol 1996, 59, 187–198. [Google Scholar]
  165. Hsing, I.M.; Xu, Y.; Zhao, W.T. Micro- and nano- magnetic particles for applications in biosensing. Electroanalysis 2007, 19, 755–768. [Google Scholar]
  166. Li, J.P.; Gao, H.D. A renewable potentiometric immunosensor based on Fe3O4 nanoparticles immobilized anti-IgG. Electroanalysis 2008, 20, 881–887. [Google Scholar]
  167. Li, Z.M.; Yang, H.F.; Li, Y.F.; Liu, Y.L.; Shen, G.L.; Yu, R.Q. Core-shell magnetic nanoparticles applied for immobilization of antibody on carbon paste electrode and amperometric immunosesning. Sens. Actuat. B 2006, 113, 956–962. [Google Scholar]
  168. Santandreu, M.; Sole, S.; Fabregas, E.; Alegret, S. Development of electrochemical immunosensing systems with renewable surfaces. Biosens. Bioelectron. 1998, 13, 7–22. [Google Scholar]
  169. Sole, S.; Alegret, S.; Cespedes, F.; Fabregas, E. Flow injection immunoanalysis based on a magnetoimmunosensor system. Anal. Chem 1998, 70, 1462–1467. [Google Scholar]
  170. Gehring, A.G.; Brewster, J.D.; Irwin, P.L.; Tu, S.I.; Van Houten, L.J. 1-Naphtyl phosphate as an enzymatic substrate for enzyme-linked immunomagnetic electrochemistry. J. Electroanal. Chem 1999, 469, 27–33. [Google Scholar]
  171. Perez, F.G.; Mascini, M.; Tothil, I.E.; Turner, A.P.F. Immunomagnetic separation with mediated flow injection analysis amperometric detection of viable Escherichia coli O157. Anal. Chem 1998, 70, 2380–2386. [Google Scholar]
  172. Dequaire, M.; Degrand, C.; Limoges, B. An immunomagnetic electrochemical sensor based on a perfluorosulfonate-coated screen-printed electrode for the determination of 2,4-dichlorooxyacetic acid. Anal. Chem 1999, 71, 2571–2577. [Google Scholar]
  173. Zacco, E.; Pividori, M.I.; Alegret, S. Electrochemical magnetoimmunosensing strategy for the detection of pesticides residues. Anal. Chem 2006, 78, 1780–1788. [Google Scholar]
  174. Ghering, A.G.; Crawford, C.G.; Mazenko, R.S.; VanHouten, L.J.; Brewster, J.D. Enzyme-linked immunomagnetic electrochemical detection of Salmonella typhimurium. J. Immunol. Methods 1996, 195, 15–25. [Google Scholar]
  175. Helali, S.; Martelet, C.; Abdelghani, A.; Maaref, M.A.; Jafrezic-Renault, N. A disposable immunomagnetic electrochemical sensor based on functionalised magnetic beads on gold surface for the detection of atrazine. Electrochim. Acta 2006, 51, 5182–5186. [Google Scholar]
  176. Varshney, M.; Li, Y.B. Interdigitated array microelectrode based impedance biosensor coupled with magnetic nanoparticle – antibody conjugates for detection of Escherichia coli O157:H7 in food samples. Biosens. Bioelectron 2007, 22, 2408–2414. [Google Scholar]
  177. Su, X.L.; Li, Y.B. A QCM immunosensor for Salmonella detection with simultaneous measurements of resonant frequency and motional resistance. Biosens. Bioelectron 2005, 21, 840–848. [Google Scholar]
  178. Centi, S.; Laschi, S.; Franek, M.; Mascini, M. A disposable immunomagnetic electrochemical sensor based on functionalised magnetic beads and carbon-based screen-printed electrodes (SPCEs) for the detection of polychlorinated biphenyls (PCBs). Anal. Chim. Acta 2005, 538, 205–212. [Google Scholar]
  179. Ho, K.C.; Tsai, P.J.; Lin, Y.S.; Chen, Y.C. Using biofunctionalized nanoparticles to probe pathogenic bacteria. Anal. Chem 2004, 76, 7162–7168. [Google Scholar]
  180. Gu, H.; Xu, K.; Xu, C.; Xu, B. Biofunctional magnetic nanoparticles for protein separation and pathogen detection. Chem. Comm 2006, 9, 941–949. [Google Scholar]
  181. Palacek, E.; Fojta, M.; Jelen, F. New approaches in the developement of DNA sensors: hybridization and electrochemical detection of DNA and RNA at two different surfaces. Bioelectrochemistry 2002, 56, 85–90. [Google Scholar]
  182. Wang, J.; Kawde, A.N.; Erdem, A.; Salazar, M. Magnetic bead-based label-free electrochemical detection of DNA hybridization. Analyst 2001, 126, 2020–2024. [Google Scholar]
  183. Kerman, K.; Matsubara, Y.; Morita, Y.; Takamura, Y. Peptide nucleic acid modified magnetic beads for intercalator based electrochemical detection of DNA hybridization. Sci. Technol. Adv. Mater 2004, 5, 351–357. [Google Scholar]
  184. Liu, R. H; Yang, J.N.; Lenigk, R.; Bonanno, J.; Grodzinski, P. Self-contained, fully integrated biochip for sample preparation, polymerase chain reaction amplification, and DNA microarray detection. Anal. Chem 2004, 76, 1824–1831. [Google Scholar]
  185. Palecek, E.; Fojita, M. Magnetic beads as versatile tools for electrochemical DNA and protein biosensing. Talanta 2007, 74, 276–290. [Google Scholar]
  186. Erdem, A.; Sayar, F.; Karadeniz, H.; Guven, G; Oszos, M.; Piskin, E. Development of streptavidin carrying magnetic nanoparticles and their applications in electrochemical nucleic acid sensor systems. Electroanalysis 2007, 19, 798–804. [Google Scholar]
  187. Grancharov, S.G.; Zeng, H.; Sun, S.H.; Wang, S.X.; O’Brien, S.; Murray, C.B.; Kirtley, J.R.; Held, G.A. Bio-functionalization of monodisperse magnetic nanoparticles and their use as biomolecular labels in a magnetic tunnel junction based sensor. J. Phys. Chem. B 2005, 109, 13030–13035. [Google Scholar]
  188. Robinson, D.B.; Persson, H.H.J.; Zeng, H.; Li, G.X.; Pourmand, N.; Sun, S.H.; Wang, S.X. DNA-functionalized MFe2O4 (M = Fe, Co, or Mn) nanoparticles and their hybridization to DNA-functionalized surfaces. Langmuir 2005, 21, 3096–3103. [Google Scholar]
  189. Stoeva, S.I.; Huo, F.; Lee, J.S.; Mirkin, C.A. Three-layer composite magnetic nanoparticle probes for DNA. J. Am. Chem. Soc 2005, 127, 15362–15363. [Google Scholar]
  190. Lermo, A.; Campoy, S.; Barbe, J.; Hernandez, S.; Alegret, S.; Pividori, M.I. In situ DNA amplification with magnetic primers for the electrochemical detection of food pathogens. Biosens. Bioelectron 2007, 22, 2010–2017. [Google Scholar]
  191. Loaiza, O.A.; Campuzano, S.; Pedrero, M.; Pedro, G.; Pingarro′n, J.M. Ultrasensitive detection of coliforms by means of direct asymmetric PCR combined with disposable magnetic amperometric genosensors. Analyst 2009, 134, 34–37. [Google Scholar]
Figure 1. (a) An external magnetic field orients the aluminum-capped Mag-MOON, causing its fluorescent excitation and observed emission to blink on and off as it rotates; (b) Scheme of an assay for the measurement of relative concentration of biotin molecules. The biotin is labeled with two types of fluorescent dyes (reproduced with permission from reference [95])
Figure 1. (a) An external magnetic field orients the aluminum-capped Mag-MOON, causing its fluorescent excitation and observed emission to blink on and off as it rotates; (b) Scheme of an assay for the measurement of relative concentration of biotin molecules. The biotin is labeled with two types of fluorescent dyes (reproduced with permission from reference [95])
Sensors 09 02976f1
Figure 2. Schematic diagram of a magnetic microflow system based on GOx functionalized biomagnetic particles with electrochemical detection for the detection of glucose (adapted from reference [161] with permission from the American Chemical Society).
Figure 2. Schematic diagram of a magnetic microflow system based on GOx functionalized biomagnetic particles with electrochemical detection for the detection of glucose (adapted from reference [161] with permission from the American Chemical Society).
Sensors 09 02976f2
Figure 3. Preparation of the immunosensor and its application in IgG determination: (1) magnetic bio-nanoparticles containing anti-IgG were attached on the surface of carbon paste electrode in the presence of magnetic field; (2) incubation of the immunosensor with IgG solutions allowed formation of the anti-IgG/IgG complex on the electrode; (3) incubation of the immunosensor in HRP-labeled anti-IgG solutions allowed formation of anti-IgG/IgG/anti-IgG-HRP complex on the electrode; (4) hydroquinone and H2O2 were added and electrode-bound IgG was determined by amperometric measurements at an potential of - 300mV (vs. SCE) (reproduced with permission from reference [167]).
Figure 3. Preparation of the immunosensor and its application in IgG determination: (1) magnetic bio-nanoparticles containing anti-IgG were attached on the surface of carbon paste electrode in the presence of magnetic field; (2) incubation of the immunosensor with IgG solutions allowed formation of the anti-IgG/IgG complex on the electrode; (3) incubation of the immunosensor in HRP-labeled anti-IgG solutions allowed formation of anti-IgG/IgG/anti-IgG-HRP complex on the electrode; (4) hydroquinone and H2O2 were added and electrode-bound IgG was determined by amperometric measurements at an potential of - 300mV (vs. SCE) (reproduced with permission from reference [167]).
Sensors 09 02976f3
Figure 4. Schematic representation of the enzyme amplification protocol: (1) probe-modified magnetic beads washing step; (2) hybridization with the target lacZ gene probe; (3) hybrid-modified magnetic beads separation and non-complementary oligonucleotide extraction; (4) enzymatic labelling with streptavidin-HRP; (5) hybrid-modified magnetic beads deposition on the TTF-Au/SPEs; (6) amperometric detection of the mediated reduction of H2O2 with TTF (reproduced, with permission, from reference [191])
Figure 4. Schematic representation of the enzyme amplification protocol: (1) probe-modified magnetic beads washing step; (2) hybridization with the target lacZ gene probe; (3) hybrid-modified magnetic beads separation and non-complementary oligonucleotide extraction; (4) enzymatic labelling with streptavidin-HRP; (5) hybrid-modified magnetic beads deposition on the TTF-Au/SPEs; (6) amperometric detection of the mediated reduction of H2O2 with TTF (reproduced, with permission, from reference [191])
Sensors 09 02976f4

Share and Cite

MDPI and ACS Style

Stanciu, L.; Won, Y.-H.; Ganesana, M.; Andreescu, S. Magnetic Particle-Based Hybrid Platforms for Bioanalytical Sensors. Sensors 2009, 9, 2976-2999. https://doi.org/10.3390/s90402976

AMA Style

Stanciu L, Won Y-H, Ganesana M, Andreescu S. Magnetic Particle-Based Hybrid Platforms for Bioanalytical Sensors. Sensors. 2009; 9(4):2976-2999. https://doi.org/10.3390/s90402976

Chicago/Turabian Style

Stanciu, Lia, Yu-Ho Won, Mallikarjunarao Ganesana, and Silvana Andreescu. 2009. "Magnetic Particle-Based Hybrid Platforms for Bioanalytical Sensors" Sensors 9, no. 4: 2976-2999. https://doi.org/10.3390/s90402976

Article Metrics

Back to TopTop