Emerging open-channel droplet arrays for biosensing

Abstract

Open-channel droplet arrays have attracted much attention in the fields of biochemical analysis, biofluid monitoring, biomarker recognition and cell interactions, as they have advantages with regard to miniaturization, parallelization, high-throughput, simplicity and accessibility. Such droplet arrays not only improve the sensitivity and accuracy of a biosensor, but also do not require sophisticated equipment or tedious processes, showing great potential in next-generation miniaturized sensing platforms. This review summarizes typical examples of open-channel microdroplet arrays and focuses on diversified biosensing integrated with multiple signal-output approaches (fluorescence, colorimetric, surface-enhanced Raman scattering (SERS), electrochemical, etc.). The limitations and development prospects of open-channel droplet arrays in biosensing are also discussed with regard to the increasing demand for biosensors.

Keywords: liquid marbles; mini-pillar platform; multiple biosensing; open-channel droplet; wettable pattern.

Figure 1.

Open-channel microdroplet array toward multiple biosensing.

Figure 2.

Open-channel droplet array for fluorescence sensing. (a) Protocell arrays for multiple clinically relevant biomarker sensing. Reproduced with permission from ref. [46]. Copyright 2021 Springer Nature. (b) Paper-based device toward human serum albumin texting. Reproduced with permission from ref. [15]. Copyright 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (c) Biogenic amine detection on the paper-based sensor array. Reproduced with permission from ref. [47]. Copyright 2021 Elsevier. (d) Multiple metal-ion recognition on the photonic-crystal microchip. Reproduced with permission from ref. [48]. Copyright 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (e) Superwettable wells toward trace DNA sensing. Reproduced with permission from ref. [49]. Copyright 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (f) Open-channel droplet transportation for biosensing. Reproduced with permission from ref. [50]. Copyright 2020 American Chemical Society.

Figure 3.

Fluorescence signal-based cell analysis. (a) Experimental procedure of the mini-pillar TeamChip for toxicology screening. Reproduced with permission from ref. [29]. Copyright 2014 Springer Nature. (b) Micropillar/microwell chip platform toward screening analysis of anticancer drug efficacy. Reproduced with permission from ref. [33]. Copyright 2014 American Chemical Society. (c) Surface-assembled microdroplets for facile production of cell arrays. Reproduced with permission from ref. [55]. Copyright 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (d) Biofilm bridge formation on patterned lubricant-infused surfaces. Reproduced with permission from ref. [56]. Copyright 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (e) Programmable merging of cell spheroids using the miniaturized droplet microarrays. Reproduced with permission from ref. [57]. Copyright 2021 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Figure 4.

Electrochemical sensing in an array of open-channel droplets. (a) Superwettable chip for cancer-biomarker electrochemical sensing in an individual droplet. Reproduced with permission from ref. [61]. Copyright 2018 American Chemical Society. (b) The sweat capture device for glucose sensing. Reproduced with permission from ref. [62]. Copyright 2019 American Chemical Society. (c) Additively manufactured biosensor toward ion-selective detection. Reproduced with permission from ref. [63]. Copyright 2019 American Chemical Society. (d) High-density droplet array toward addressable electrochemical measurement. Reproduced with permission from ref. [64]. Copyright 2017 American Chemical Society.

Figure 5.

Droplet management for colorimetric detection. (a) 96-well microtiter array for detection of saccharides. Reproduced with permission from ref. [70]. (b) Liquid marbles for colorimetric enzymatic process monitoring. Reproduced with permission from ref. [71]. Copyright 2021 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (c) Droplet precise self-splitting for simultaneous multi-detection. Reproduced with permission from ref. [72]. Copyright 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (d) Open-channel droplet manipulation for multiplex bioassay. Reproduced with permission from ref. [73]. Copyright 2018 American Chemical Society. (e) Superwettable and flexible bands toward sweat sampling and monitoring. Reproduced with permission from ref. [74]. Copyright 2019 American Chemical Society. Copyright 2021 American Chemical Society. (f) Microchamber bandages toward multiplexed rapid urinalysis. Reproduced with permission from ref. [75]. Copyright 2020 Elsevier.

Figure 6.

Open-channel droplet SERS signal acquisition. (a) High-throughput droplet array for breast-cancer-marker sensing. Reproduced with permission from ref. [80]. (b) Droplet-guiding platform toward real-time SERS detection. Reproduced with permission from ref. [24]. Copyright 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (c) Liquid marbles for multiple molecular detection. Reproduced with permission from ref. [81]. Copyright 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (d) The SERS diagnostic platform for urine metabolite sensing. Reproduced with permission from ref. [82]. Copyright 2020 American Chemical Society. Copyright 2020 Elsevier.

Figure 7.

Open-channel droplet array for mass spectrometry. (a) Swan-shaped MS probe for sample separation and analysis. Reproduced with permission from ref. [84]. Copyright 2020 American Chemical Society. (b) Smart MALDI-MS plate for protein purification and analysis. Reproduced with permission from ref. [85]. Copyright 2018 American Chemical Society. (c) Droplet microarray toward liquid extraction surface MS analysis. Reproduced with permission from ref. [86]. Copyright 2018 American Chemical Society. (d) MS imaging of nanoliter-scale cell assays. Reproduced with permission from ref. [87]. Copyright 2021 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Figure 8.

Multi-technology coupling toward biosensing in droplets. (a) 3D plasmonic liquid marble for molecular-level spectroelectrochemical investigation. Reproduced with permission from ref. [13]. Copyright 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (b) ‘On-line’ detection based on magnetic liquid marble. Reproduced with permission from ref. [39]. Copyright 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (c) Nanodendritic gold/graphene-based droplet biosensor for tri-modal miRNA sensing. Reproduced with permission from ref. [91]. Copyright 2019 The Royal Society of Chemistry. (d) Jigsaw-like mini-pillar platform for multi-mode biosensing. Reproduced with permission from ref. [92]. Copyright 2021 Elsevier.