Argon Enclosed Droplet Based 3D Microfluidic Device Online Coupled with Time-Resolved ICPMS for Determination of Cadmium and Zinc in Single Cells Exposed to Cadmium Ion

Abstract

Time-resolved (TRA)-ICPMS has become a booming subfield of single-cell analysis tools in recent years, while generation of single cells remains the major challenge. Microfluidic devices reveal their great capability and potential in encapsulation of single cells into water droplets. However, current strategies to pinch off droplets require a specific oil phase, which is not compatible to conventional ICPMS and makes the signal of cells in the water phase susceptible. Herein, we built a 3D water-in-gas microfluidic device (3D W/G MFD) with commercially available components, producing single cell droplet enclosed by argon gas. By simply tuning the flow rate of gas and water, the droplets were generated to encapsulate single cells, which significantly reduced the probability of the single signal coming from multiple cells by 1 or 2 orders of magnitude compared to direct injection. The developed oil-free 3D W/G MFD was more friendly to online coupling with TRA-ICPMS than water-in-oil devices. The effect of Cd2+ on HepG2 cells was studied by single cell detecting total Zn with 3D W/G MFD-TRA-ICPMS, and the variation of labile Zn was explored by flow cytometry with an N-(6-methoxy-8-quinolyl)-p-toluenesulfonamide probe. To the best of our knowledge, this work pioneered the exploration of variation in cellular metal content and speciation at the single-cell level, compensating for the deficiency of speciation analysis based on TRA-ICPMS and providing new insights into exploring the complexity of biology.

Filter-Assisted Separation of Multiple Nanomaterials: Mechanism and Application in Atomic/Mass Spectrometry/Fluorescence Label-Free Multimode Bioassays

“…Atomic spectrometry (AS) (atomic absorption spectrometry, atomic emission spectrometry, and atomic fluorescence spectrometry (AFS)) and inductively coupled plasma mass spectrometer (ICP-MS) have been widely applied in environmental monitoring, food safety testing, and other industries. , In view of the many advantages of AS and the need for precise detection methods in biomedicine, AS has been widely used in bioassay. − Within this field, Zhang et al pioneered the ICP-MS-based bioassay for a sensitive and accurate determination of proteins using antibodies as recognition probes. , Subsequently, researchers introduced biorecognition probes such as nucleic acid aptamers and peptides into AS, and developed various biomolecule detection methods, which greatly expanded the application of AS in bioanalysis. , Although these AS bioassay methods hold the advantages of high sensitivity, good specificity, and accuracy, labeling and signal molecule separation are still required, which adds complexity and thus puts them at a disadvantage …”

Standard-free single magnetic bead evaluation: a stable nanoplatform for prostate disease differentiation

“…Endowed with high throughput and resolution, single particle ICP-MS (sp-ICP-MS) has gained great attention in multiplex biological practice and single-cell analysis. [18][19][20][21][22][23][24] Based on the theory in a typical sp-ICP-MS analysis, nanoparticles are injected one by one into the detector where only one nanoparticle is measured during each reading period. Beneting from ample metal content in one nanoparticle, sensitivity is largely improved in heterogeneous bioassays where absolute quantications can be easily achieved by measuring the total numbers of target-specic nanoparticles.…”

Negative Magnetophoresis Focusing Microchips Online-Coupled with ICP–MS for High-Throughput Single-Cell Analysis

“…The above approaches demonstrate that the droplet microchip/microdevice is capable of encapsulating single cells in droplets for online ICP–MS detection and exhibits good application potential in accurate single-cell analysis. However, the sample throughput for droplet microchips/microdevices in single-cell analysis is about several dozens of cells per minute, − and further improvement is limited under the conditions of a low cell density, which guarantees no more than one cell encapsulated in one droplet. In addition, the oil phase with a high carbon content is incompatible with ICP–MS detection; thus, the available water-in-oil droplet system is also very limited.…”