3D-printed capillaric ELISA-on-a-chip with aliquoting

Lab Chip. 2023 Mar 14;23(6):1547-1560. doi: 10.1039/d2lc00878e.

Abstract

Sandwich immunoassays such as the enzyme-linked immunosorbent assay (ELISA) have been miniaturized and performed in a lab-on-a-chip format, but the execution of the multiple assay steps typically requires a computer or complex peripherals. Recently, an ELISA for detecting antibodies was encoded structurally in a chip thanks to the microfluidic chain reaction (Yafia et al. Nature, 2022, 605, 464-469), but the need for precise pipetting and intolerance to commonly used surfactant concentrations limit the potential for broader adoption. Here, we introduce the ELISA-on-a-chip with aliquoting functionality that simplifies chip loading and pipetting, accommodates higher surfactant concentrations, includes barrier channels that delay the contact between solutions and prevent undesired mixing, and that executed a quantitative, high-sensitivity assay for the SARS-CoV-2 nucleocapsid protein in 4×-diluted saliva. Upon loading the chip using disposable pipettes, capillary flow draws each reagent and the sample into a separate volumetric measuring reservoir for detection antibody (70 μL), enzyme conjugate (50 μL), substrate (80 μL), and sample (210 μL), and splits washing buffer into 4 different reservoirs of 40, 40, 60, and 20 μL. The excess volume is autonomously drained via a structurally encoded capillaric aliquoting circuit, creating aliquots with an accuracy of >93%. Next, the user click-connects the assay module, comprising a nitrocellulose membrane with immobilized capture antibodies and a capillary pump, to the chip which triggers the step-by-step, timed flow of all aliquoted solutions to complete the assay in 1.5 h. A colored precipitate forming a line on a nitrocellulose strip serves as an assay readout, and upon digitization, yielded a binding curve with a limit of detection of 54 and 91 pg mL-1 for buffer and diluted saliva respectively, vastly outperforming rapid tests. The ELISA chip is 3D-printed, modular, adaptable to other targets and assays, and could be used to automate ELISA in the lab; or as a diagnostic test at the point of care with the convenience and form factor of rapid tests while preserving the protocol and performance of central laboratory ELISA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies
  • Antibodies, Immobilized
  • COVID-19* / diagnosis
  • Collodion
  • Enzyme-Linked Immunosorbent Assay / methods
  • Humans
  • Lab-On-A-Chip Devices
  • Printing, Three-Dimensional
  • SARS-CoV-2

Substances

  • Collodion
  • Antibodies
  • Antibodies, Immobilized