Lab-on-a-chip: an advanced technology for the modernization of traditional Chinese medicine

Abstract

Benefiting from the complex system composed of various constituents, medicament portions, species, and places of origin, traditional Chinese medicine (TCM) possesses numerous customizable and adaptable efficacies in clinical practice guided by its theories. However, these unique features are also present challenges in areas such as quality control, screening active ingredients, studying cell and organ pharmacology, and characterizing the compatibility between different Chinese medicines. Drawing inspiration from the holistic concept, an integrated strategy and pattern more aligned with TCM research emerges, necessitating the integration of novel technology into TCM modernization. The microfluidic chip serves as a powerful platform for integrating technologies in chemistry, biology, and biophysics. Microfluidics has given rise to innovative patterns like lab-on-a-chip and organoids-on-a-chip, effectively challenging the conventional research paradigms of TCM. This review provides a systematic summary of the nature and advanced utilization of microfluidic chips in TCM, focusing on quality control, active ingredient screening/separation, pharmaceutical analysis, and pharmacological/toxicological assays. Drawing on these remarkable references, the challenges, opportunities, and future trends of microfluidic chips in TCM are also comprehensively discussed, providing valuable insights into the development of TCM.

Keywords: Active ingredient screening; Compatibility of traditional Chinese medicine; Microfluidic chip; Pharm-lab-on-a-chip; Quality control; Traditional Chinese medicine.

Fig. 1

Illustration of this review profile

Fig. 2

Some advanced theories and strategies in characterizing TCM’s efficacy mechanism. A Traditional Chinese medicine chemomics [4]; B Spectrum-effect relationships [33]; C Chinmedomics [39], Copyright, 2020, Elsevier; D Network pharmacology [43], Copyright, 2013, Elsevier; E Integrative pharmacology-based TCM [44]

Fig.3

Typical structures and fabrication of microfluidics. A Droplet simulation [51]; B Droplet microfluidics for single cell analysis [65]; C Laminar flow on chips [66], Copyright, 2022, Elsevier; D Christmas tree model [67]; E PDMS chip fabrication [68], Copyright, 2022, Elsevier; F Six typical glass microstructure fabrication techniques [55]; G 3D Printed microfluidic chip [69]

Fig.4

The organ/tissue mimic achieved by microfluidics. A Single-cell capture and analysis [110]; B Cells co-culture [123], Copyright, 2020, Elsevier; C Mimicking intestine on a chip [124], Copyright, 2017, Elsevier; D Biomimetic of blood vessels [80], Copyright, 2017, John Wiley and Sons; E Biomimetic of 3D glomerulus [125]; F Multi-organoids culture model [107]

Fig.5

Proposed elucidation pattern of TCM compatibility theories using Pharm-on-a-chip

Fig.6

Demonstration of microfluidic chips in TCM. A Ligand fishing and quality control chip [108]. B Concentration gradient chip [144], Copyright, 2019, Elsevier; C Simulating of tumor microenvironment to evaluation of antimetastatic effects of TCM [147], Copyright, 2014, American Chemical Society; D Efficacy evaluation of TCM by biomimetic BBB chip [133], Copyright, 2023, Elsevier. E Endogenous and exogenous metabolites of cells were identified and monitored in real-time by the Chip-MS system [157], Copyright, 2022, American Chemical Society; F Cells co-culture chip for efficacy assay of TCM metabolites [106]

Fig.7

Application framework of microfluidic chips for TCM