Full Length ArticleImproved lateral flow strip based on hydrophilic−hydrophobic SERS substrate for ultra−sensitive and quantitative immunoassay
Graphical abstract
Introduction
Surface−enhanced Raman scattering (SERS) technique with promising fingerprint recognition and ultra−high sensitivity has been confirmed as a powerful protocal in food safety, chemical analysis, medical detection, and pollutant monitoring [1], [2], [3], [4], [5]. In fact, a possible significant progress in the practical application of SERS technique is mainly determined by the rational synthesis of substrates based on noble metal nanoparticles (NPs) with unique electromagnetic enhancement ability [6], [7], [8], [9]. In the field of biomedical monitoring, SERS−based lateral flow immunoassay (LFIA), composed by several pieces of assembled paper−based material on a plastic backboard, has become one of the exhaustively used protocols for point−of−care testing (POCT) diagnostics due to its low cost, promising convenience, rapid detection, and user−friendly format [10], [11], [12], [13]. In a typical test based on sandwich immunostructure, a drop of immunoprobes is dropped onto the strip and it moves through the membrane by capillary force to reach the test or control zone labelled with target antigens or bare antibodies. However, the major disadvantage of this assay is its limited accumulative and quantitative abilities, which make these LFIA biosensors less attractive.
Besides the similar flexibility, portability, and simplicity to paper−based supports, the most superiority of polydimethylsiloxane (PDMS) for serving as the ideal matrix of plasmonic NPs lies in not only its intrinsic Raman peaks but also its naturally hydrophobic surface. In fact, the intrinsic Raman peaks could be utilized as internal standard (IS) to effectively realize quantitative test and the hydrophobic surface can prevent the random spreading of analyte solution to fully concentrate them [14], [15], [16], [17], [18] Particularly, a novel hydrophilic−hydrophobic assembly substrate has been designed to facilitate the uniform distribution of analytes within the hydrophilic area surrounded by hydrophobic zone, which can hinder coffee−ring effect and enable more accurate detection [19]. Although some SERS substrates using PDMS film as support have been developed [14], [20], it should be noted that there is nearly no report about versatile LFIA with both Raman IS and enrichment ability based on the PDMS. If such a novel platform was utilized in the practical biomedical assay, highly sensitive and reliable quantitative results could be definitely imagined.
In this communication, a novel PDMS−based LFIA was proposed for the ultra−sensitive and quantitative SERS analysis of Ferritin (FER), a typical kind of tumor markers that play a crucial role in the efficient detection of liver cancer (Scheme 1). In this innovative LFIA, the microdroplets of analytes could flow smoothly in the hydrophobic surface of PDMS and then captured and enriched by the test line of hydrophilic Ag surface. Without the coffee−ring effect, such a hydrophilic−hydrophobic SERS platform would achieve an on−site trace FER detection with a pretty good limit of detection (LOD, 0.41 pg/mL), assisted by the raspberry−like Au NPs (RANPs) as immunoprobes. Moreover, the corresponding linear fittings were steadily improved by rationally using the Raman signals of PDMS as a reference. We believe such a novel PDMS−based LFIA would pave a new way for ultra−sensitive and quantitative analysis in the POCT setting.
Section snippets
Preparation of hydrophilic−hydrophobic Ag/PDMS immunosubstrate
Ag NPs was selectively coated onto the specific areas of PDMS matrix assisted by homemade mask to create three hydrophilic regions using a typical magnetron sputtering apparatus (0.4 Pa, 40 W). In order to prepare the immunosubstrate, the captured anti−FER in PBS solution (20 μL, 0.2 mg/mL) was modified onto the Ag/PDMS through incubation (4 °C, 12 h). BSA was then used to cover the extra bare sites of the matrix. After being modified by captured anti−FER and target FER, one of the hydrophilic
Results and discussion
It is well accepted that the SERS performance of noble metal depends on its configuration parameters such as surface morphology, roughness, and homogeneity [21], [22]. In this regard, the optimal decoration amount of Ag for obtaining appropriate Raman enhancement effect was firstly investigated after the formation of hydrophilic−hydrophobic Ag/PDMS substrates. Fig. 1a−d illustrate the morphologies of Ag/PDMS substrates prepared under different sputtering time (3 to 12 s). As can be identified,
Conclusion
In summary, with the aim to improve the sensitivity and quantitative degree of SERS−based detection of FER, we designed a novel LFIA mediated by a sophisticated hydrophilic−hydrophobic Ag/PDMS substrate. Pretty high SERS intensity with EF of 1.93 × 106 was facilitated by such a hydrophilic−hydrophobic strategy. More meaningfully, analytes during rolling could be stopped in the hydrophilic lines (Ag) surrounded by hydrophobic PDMS regions for more efficient anchoring. Supported by the
CRediT authorship contribution statement
Yi Ma: Investigation, Methodology, Writing - original draft. Hongmei Liu: Investigation. Ying Chen: Investigation. Chenjie Gu: Investigation. Guodong Wei: Investigation. Tao Jiang: Writing - review & editing, Project administration.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
This work was supported by Natural Science Foundation of Zhejiang Province (Grant No. LY19F050002), Natural Science Foundation of Ningbo (Grant No. 2018A610316), and K.C. Wong Magna Fund in Ningbo University, China.
References (35)
- et al.
Designing of a novel gold nanodumbbells SERS substrate for detection of prohibited colorants in drinks
Appl. Surf. Sci.
(2016) - et al.
SERS-encoded nanocomposites for dual pathogen bioassay
J. Mater. Sci. Technol.
(2020) - et al.
Classification analyses for prostate cancer, benign prostate hyperplasia and healthy subjects by SERS-based immunoassay of multiple tumour markers
Talanta
(2018) - et al.
The synthesis of four–layer gold–silver–polymer–silver core-shell nanomushroom with inbuilt Raman molecule for surface–enhanced Raman scattering
Appl. Surf. Sci.
(2017) - et al.
A SERS-based lateral flow assay biosensor for quantitative and ultrasensitive detection of interleukin-6 in unprocessed whole blood
Biosens. Bioelectron.
(2019) - et al.
Intrinsic Raman signal of polymer matrix induced quantitative multiphase SERS analysis based on stretched PDMS film with anchored Ag nanoparticles/Au nanowires
Chem. Eng. J.
(2020) - et al.
SERS-based multiplex immunoassay of tumor markers using double SiO2@Ag immune probes and gold-film hemisphere array immune substrate
Colloid. Surface. A
(2018) - et al.
Highly sensitive immunoassay based on SERS using nano-Au immune probes and a nano-Ag immune substrate
Talanta
(2014) - et al.
Biomolecule induced nanoparticle aggregation: effect of particle size on interparticle coupling
J. Colloid Interf. Sci.
(2007) - et al.
Non-resonance SERS effects of silver colloids with different shapes
Chem. Phys. Lett.
(2007)
Osmium organosol on DNA: application in catalytic hydrogenation reaction and in SERS studies
Ind. Eng. Chem. Res.
Monitoring 2,3',5,5'-tetrachlorobiphenyl with a rapid and sensitive environmental aptamer sensor
Analyst
Construction of long narrow gaps in Ag nanoplates
J. Am. Chem. Soc.
Preparation of gap-controlled monodispersed Ag nanoparticles by amino groups grafted on silica microspheres as a SERS substrate for the detection of low concentrations of organic compounds
Ind. Eng. Chem. Res.
Chiral AuCuAu heterogeneous nanorods with tailored optical activity
Adv. Funct. Mater.
Magnetic SERS strip for sensitive and simultaneous detection of respiratory viruses
ACS Appl. Mater. Inter.
Quantifying the numbers of gold nanoparticles in the test zone of lateral flow immunoassay strips
ACS Appl. Nano Mater.
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