One-droplet saliva detection on photonic crystal-based competitive immunoassay for precise diagnosis of migraine

Abstract

Migraine exhibits a substantial prevalence worldwide. The current diagnostic criteria rests exclusively on clinical characteristics without any objective and reliable means. The calcitonin gene-related peptide (CGRP), as a biomarker for distinguishing migraine, undergoes swift degradation, featuring a half-life of under 10 min, which poses a significant challenge to the point-of-care testing of CGRP in clinical application. Here, a photonic crystal (PC)-based biochip has been developed to detect CGRP via the fluorescence competition assay. The chip integrates the functionalities of fluorescence enhancement and hydrophilic–hydrophobic patterning enrichment, enabling rapid and sensitive detection of CGRP. After investigating the optimal enhancement distance of fluorescence near PCs, the chip allows CGRP detection using <30 µL of saliva at room temperature within 10 min. A minimum detection limit of 0.05 pg/mL is achieved. Furthermore, CGRP concentrations in the saliva of 70 subjects have been tested by PC biochips. The results exhibit strong concordance with the enzyme-linked immunosorbent assay (ELISA), demonstrating a linear correlation coefficient of R² of 0.97. This sensitive detection of markers within such a short duration surpasses the capacities of ELISA, which paves the way for establishing a precise diagnostic framework integrating clinical phenotypes and biomarkers for migraine.

Keywords

calcitonin gene-related peptide / migraine biomarkers / photonic crystals / point-of-care testing

References

[1] Ailani J, Burch RC, Robbins MS, Board of Directors of the American Headache Society. The American Headache Society Consensus Statement: update on integrating new migraine treatments into clinical practice. Headache: The Journal of Head and Face Pain. 2021; 61(7): 1021-1039.

[2] GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019; 18(5): 459-480.

[3] Yu S, Liu R, Zhao G, et al. The prevalence and burden of primary headaches in China: a population-based door-to-door survey. Headache. 2012; 52(4): 582-591.

[4] Liu R, Yu S, He M, et al. Health-care utilization for primary headache disorders in China: a population-based door-to-door survey. J Headache Pain. 2013; 14(1): 47.

[5] Edvinsson L. The CGRP pathway in migraine as a viable target for therapies. Headache. 2018; 58(suppl 1): 33-47.

[6] Charles A. The pathophysiology of migraine: implications for clinical management. Lancet Neurol. 2018; 17(2): 174-182.

[7] Ashina M. Migraine. N Engl J Med. 2020; 383(19): 1866-1876.

[8] Russo AF, Hay DL. CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond. Physiol Rev. 2023; 103(2): 1565-1644.

[9] Lassen L, Haderslev P, Jacobsen V, Iversen H, Sperling B, Olesen J. CGRP may play a causative role in migraine. Cephalalgia. 2002; 22(1): 54-61.

[10] Ashina M, Bendtsen L, Jensen R, Schifter S, Jansen-Olesen I. Olesen J. Plasma levels of calcitonin gene-related peptide in chronic tension-type headache. Neurology. 2000; 55(9): 1335-1340.

[11] Cernuda-Morollon E, Larrosa D, Ramon C, Vega J, Martinez-Camblor P. Pascual J. Interictal increase of CGRP levels in peripheral blood as a biomarker for chronic migraine. Neurology. 2013; 81(14): 1191-1196.

[12] Zhang W, Cunningham BT. Fluorescence enhancement by a photonic crystal with a nanorod-structured high index layer. Appl Phys Lett. 2008; 93(13): 1-3.

[13] Baker JE, Sriram R, Miller BL. Two-dimensional photonic crystals for sensitive microscale chemical and biochemical sensing. Lab Chip. 2015; 15(4): 971-990.

[14] Wang J, Pinkse PWH, Segerink LI, Eijkel JCT. Bottom-up assembled photonic crystals for structure-enabled label-free sensing. ACS Nano. 2021; 15(6): 9299-9327.

[15] Wang Y, Shang L, Bian F, et al. Hollow colloid assembled photonic crystal clusters as suspension barcodes for multiplex bioassays. Small. 2019; 15(13): e1900056.

[16] Inan H, Poyraz M, Inci F, et al. Photonic crystals: emerging biosensors and their promise for point-of-care applications. Chem Soc Rev. 2017; 46(2): 366-388.

[17] Su M, Song Y. Printable smart materials and devices: strategies and applications. Chem Rev. 2022; 122(5): 5144-5164.

[18] Lian Z, Wu T, Wang H, et al. At-home COVID-19 rapid antigen test down to 0.03 pg/mL of nucleocapsid protein. Small. 2023; 19(28): e2301162.

[19] Joh DY, Hucknall AM, Wei Q, et al. Inkjet-printed point-of-care immunoassay on a nanoscale polymer brush enables subpicomolar detection of analytes in blood. Proc Natl Acad Sci U S A. 2017; 114(39): E7054-E7062.

[20] Wu P, Wang J, Jiang L. Bio-inspired photonic crystal patterns. Mater Horizons. 2020; 7(2): 338-365.

[21] Zhang X, Chen G, Bian F, Cai L, Zhao Y. Encoded microneedle arrays for detection of skin interstitial fluid biomarkers. Adv Mater. 2019; 31(37): e1902825.

[22] Tan H, Lyu Q, Xie Z, et al. Metallosupramolecular photonic elastomers with self-healing capability and angle-independent color. Adv Mater. 2019; 31(6): e1805496.

[23] Kuang M, Wang J, Bao B, et al. Inkjet printing patterned photonic crystal domes for wide viewing-angle displays by controlling the sliding three phase contact line. Adv Opt Mater. 2014; 2(1): 34-38.

[24] Wang Y, Li Y, Zhang Y, Ren K, Ju H, Liu Y. Express and sensitive detection of multiple miRNAs via DNA cascade reactors functionalized photonic crystal array. Sci China Chem. 2020; 63(5): 731-740.

[25] Chi J, Wu Y, Qin F, et al. All-printed point-of-care immunosensing biochip for one drop blood diagnostics. Lab Chip. 2022; 22(16): 3008-3014.

[26] Chi J, Su M, Xue B, et al. Fast and sensitive detection of protein markers using an all-printing photonic crystal microarray via fingertip blood. ACS Sens. 2023; 8(4): 1742-1749.

[27] Alpuente A, Gallardo VJ, Asskour L, Caronna E, Torres-Ferrus M. Pozo-Rosich P. Salivary CGRP and erenumab treatment response: towards precision medicine in migraine. Ann Neurol. 2022; 92(5): 846-859.

[28] Alpuente A, Gallardo VJ, Asskour L, Caronna E, Torres-Ferrus M. Pozo-Rosich P. Salivary CGRP can monitor the different migraine phases: CGRP (in)dependent attacks. Cephalalgia. 2022; 42(3): 186-196.

[29] Brossard FSF, Pecunia V, Ramsay AJ, Griffiths JP, Hugues M, Sirringhaus H. Inkjet-printed nanocavities on a photonic crystal template. Adv Mater. 2017; 29(47): 1770335.

[30] Qin M, Huang Y, Li Y, et al. A rainbow structural-color chip for multisaccharide recognition. Angew Chem Int Ed. 2016; 55(24): 6911-6914.

[31] Hou J, Zhang H, Yang Q, Li M, Song Y, Jiang L. Bio-inspired photonic-crystal microchip for fluorescent ultratrace detection. Angew Chem Int Ed. 2014; 53(23): 5791-5795.

[32] de Vries Lentsch S, Verhagen IE, van den Hoek TC, MaassenVanDenBrink A, Terwindt GM. Treatment with the monoclonal calcitonin gene-related peptide receptor antibody erenumab: a real-life study. Eur J Neurol. 2021; 28(12): 4194-4203.

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