Molecularly Imprinted Materials
5.4 Sensors
As well as separation technologies by MIPs, a great number of sensors have been devel- oped by several modifications and improvements of the typical MIP synthesis. Especially, electrochemical detections with conductive carbons and inorganic NPs were widely applied for hybrid materials with MIPs. Guo et al. used 2‐oxindole as dummy template and p‐aminothiophenol (p‐ATP) as functional monomers, combined with the high
TEOS
O
O O
O O
OH O MeHg IIMN
MeHg IIMN
Magnet separation CH3Hg+ elution CH3Hg+ removing
PDC-CH3Hg+
MMA, TMPTM, AIBN Polymerization Fe3O4@SiO2-γ-MAPS
Fe3O4@SiO2 Fe3O4 Fe3O4
Fe3O4 Fe3O4
Fe3O4
CH3Hg+ extraction and pre-concentration
CH3Hg+ PDC
CE-ICP-MS detection
N C S
SH N C S
Hg CH3 S
S S C N O
O O
OH O
Hg HO HO
O O O
γ-MAPS Si
Figure 5.3 Experimental principle of preparing CH3Hg‐ion imprinted magnetic nanoparticles (CH3HgIIMN) and detecting CH3Hg in water samples with capillary electrophoresis–inductively coupled plasma‐mass spectrometry (CE‐ICP‐MS) together with CH3Hg IIMN. Source: Reprinted from Reference [36], © Elsevier B.V. Reproduced with permission of Elsevier.
Molecularly Imprinted Materials 167
sensitivity of electrochemical detection, to achieve a specific and efficient detection of patulin in fruit juice [38]. In addition, carbon dots and chitosan were used as the modi- fying material to improve the electron‐transfer rate, expand the electroactive surface of a glassy carbon electrode, and enhance the signal strength. The Au─S bond and hydro- gen bond were employed to complete the assembly of the p‐ATP and 2‐oxindole on the surface of the electrode. Then, polymer membranes were formed by electropolymeriza- tion in a polymer solution containing p‐ATP. The sensor had a high‐speed real‐time detection capability and has become a new, promising method for the detection of patulin. Prasad et al. have reported a typical synthesis of a nanocomposite of functional- ized graphene quantum dots and imprinted polymer at the surface of screen‐printed carbon electrode using N‐acryloyl‐4‐aminobenzamide, as a functional monomer, and an anticancer drug, ifosfamide, as template molecules [39]. Graphene QDs in nanocom- posites induced the electrocatalytic activity by lowering the oxidation overpotential of a test analyte and thereby amplifying electronic transmission, without any interfacial barrier between the film and the electrode surface. The proposed sensor is practically applicable to the ultratrace evaluation of ifosfamide in real (biological/pharmaceutical) samples with a detection limit as low as 0.11 ng ml−1 (S/N = 3), without any matrix effect, cross‐reactivity, and false‐positives. The authors also studied the use of carbon based materials for electrochemical detection with MIPs, such as fullerene (C60‐ monoadduct)‐based, water‐compatible, imprinted micelles for electrochemical determination of chlorambucil [40] and surface imprinted nanospheres consisting of pencil graphite electrode using the inverse suspension polymerization method for elec- trochemical ultra‐sensing of dacarbazine [41]. Apart from carbon materials, Au parti- cles are often utilized as the platform of electro detection with MIPs. Yang et al.
developed a novel imprinted sensor for ultra‐trace cholesterol detection based on the electropolymerized aminothiophenol MIP on a glassy carbon electrode modified with dopamine@graphene and bioinspired Au microflowers [42]. The bioinspired Au micro- flowers were formed by Au NPs (AuNPs) and wrapped with bionic polydopamine film through the electropolymerization method. Liu et al. reported a novel electrochemical detection platform established by integrating the molecular imprinting technique with a microfluidic chip and applied it for trace measurement of three therapeutic drugs [43].
In the detection cell of the chip, a Pt wire was used as the counter electrode and refer- ence electrode, and an Au─Ag alloy microwire with a 3D nanoporous surface modified with electro‐MIP film as the working electrode. The system was applied for 24 h moni- toring of drug concentration in plasma after administration of warfarin sodium in rabbit, and the corresponding pharmacokinetic parameters were obtained. Additionally, the microfluidic chip was successfully adopted to analyze cyclophosphamide and carbamazepine, implying good versatility.
As shown above, electrochemical sensors are very useful and the sensitivity is very high. However, optical detection such as fluorescence detection is very attractive for further simple and ease of detection of target compounds. Amjadi et al. designed a dual‐
emission mesoporous structured molecularly imprinted sensor for specific recognition and sensitive ratiometric detection of diniconazole [44]. In this probe, a carbon dot‐
doped silica core served as a reference and provided a built‐in correction for environ- mental effects. CdTe/CdS QDs were encapsulated in the pores of the mesoporous silica and provide an analytical signal. The applicability of the developed method for analysis of real samples was evaluated through the determination of diniconazole in soil, river
water, and wastewater samples and satisfactory recoveries were obtained. Li et al. studied a new type of sensing protocol, based on a high precision metrology of quantum weak measurement for a MIP‐sensor [45] (Figure 5.4). A weak measurement system exhibits high sensitivity to the optical phase shift corresponding to the refractive index change, which is induced by the specific capture of target protein molecules with their recogni- tion sites. The recognition process can be finally characterized by the central wavelength shift of output spectra through weak value amplification. Patra et al. described the prepa- ration of a nanohybrid by a combination of the 2D graphene sheet and 0D graphene quantum dots (GQDs). The GQDs were prepared from natural green precursors, i.e.
carrot juice, by the one‐step hydrothermal process [46]. To get the maximum fluores- cence property from nanohybrid, the graphene sheets were chemically doped with CdS.
In designing a MIP, two biocompatible monomers (cystine monomer and N‐vinyl capro- lactam) were used, which provided biodegradability to the polymer matrix. The MIP shows a very good selectivity toward the detection of nimesulide with an LOD as low as 6.65 ng l−1 (S/N = 3). Additionally, Li et al. reported the fabrication of mesoporous‐struc- tured ratiometric molecularly imprinted sensors using a combined surface‐imprinted and ratiometric fluorescence method [47]. The sensors were subsequently examined in the selective and sensitive determination of 2,4,6‐trinitrophenol (TNP). In the surface imprinting process, cetyltrimethylammonium bromide was employed to create a mesoporous‐structured silica to promote quenching of 2‐acrylamide‐6‐methoxybenzo- thiazole by TNP via resonance energy transfer, thereby enhancing the sensitivity of the sensor (Figure 5.5). Under optimum conditions, the ratiometric fluorescence MIP sen- sors achieved a detection limit of 43 nM within 3 min.
As other interesting applications in sensor technologies, Rong et al. [48] reported Ag‐LaFeO3 MIPs (ALMIPs), which provided special recognition sites to methanol.
Then ALMIPs fiber 1, fiber 2, and fiber 3 were prepared using filter paper, silk, and carbon fibers template, respectively. The ALMFs (Ag‐LaFeO3 molecular fibers) exhibit a cellulosic structure with a hollow or solid rod consisting of single fiber. The ALMIP fibers (fiber 1, fiber 2, and fiber 3) showed excellent selectivity and good response to
Linear polarizer
SLD
Reference channel
Mirror
PBS PBS
Linear polarizer
Spectrograph Mirror
Gaussian filter
y x
z
V
H
Measuring channel
Figure 5.4 Schematic diagram of the quantum weak measurement system. Source: Reprinted from Reference [45], © Elsevier B.V. Reproduced with permission of Elsevier.
Molecularly Imprinted Materials 169
methanol. The responses to 5 ppm methanol and the optimal operating temperature of ALMIPs fibers were 23.5 and 175 °C (fiber 1), 19.67 and 125 °C (fiber 2), 17.59 and 125 °C (fiber 3), while lower responses (≤10, 3, 2) to other test gases including formaldehyde, acetone, ethanol, ammonia, gasoline, and benzene were measured. Liang et al. demon- strated that biological analytes such as proteins and cells were rapidly, sensitively, and selectively detected without chemical labeling by using polymeric membrane ion‐selective electrodes, which have been extensively used in clinical analysis [49]. The proposed approach was based on the blocking mechanism in which the recognition reaction between the mussel‐inspired surface imprinted polymer and bioanalytes blocks the flux of the indicator ion from the sample solution to the sensing membrane (Figure 5.6). The proposed biomimetic sensing platform may have the potential to quantify many other targets such as DNA or virus, even tissues, through the use of suitable surface MIPs.
MPS TEOS
NH3H2O TEOS, NH3H2O
Remove TNP and CTAB
AMBA&SiO2
Wavelength Wavelength
FL
FL
TNP CTAB QDs
Figure 5.5 Schematic illustrations for the preparation process of fluorescence MIP (FL‐MIP) sensors.
Source: Reprinted from Reference [47], © Elsevier B.V. Reproduced with permission of Elsevier.
Polymerization
Without (a)
(b)
Current Current
Without With
With Iz–
Iz–
Iz–
Iz–
Iz–
Time
= Biological species
= Imprinting monomers
= Indicator ion
EMF
Rebinding Removal Imprinted layer
Iz–-ISE membrane
Imprinted layer Iz–-ISE membrane
Imprinted layer Iz–-ISE membrane
Imprinted layer Iz–-ISE membrane Iz–-ISE membrane
Figure 5.6 Schematic of (a) the construction of mussel‐inspired surface‐imprinted‐layer modified potentiometric sensor and (b) chronopotentiometric detection of a bioanalyte. Source: Reprinted with permission from [49], © Wiley. Reproduced with permission of John Wiley & Sons.
As mentioned above, the MIP‐based sensor technologies have been rapidly developed, especially in bioanalytical fields. In the near future, bio‐related NPs (such as exosome) and living cells will be able to be detected by MIP‐sensors.