Integrating Low-Voltage Microfluidics With On-Chip Electrospray Ionization for Miniaturized Protein Analysis

Area of Science:

• Analytical Chemistry
• Biotechnology
• Microfluidics

Background:

• Low-input proteomics demands analytical methods minimizing sample loss and dilution.
• Electrokinetic microfluidics provides precise control over sample manipulation in compact platforms.
• Integrating microfluidics with mass spectrometry is key for sensitive protein analysis.

Purpose of the Study:

• To review the integration of electrokinetic microfluidics with on-chip electrospray ionization (ESI) for low-input proteomics.
• To discuss electric-field-driven sample handling combined with mass spectrometric detection.
• To highlight advancements and future directions in miniaturized protein analysis.

Main Methods:

• Review of fundamental electrokinetic mechanisms: electroosmotic flow (EOF), dielectrophoresis (DEP), electrowetting-on-dielectric (EWOD), electrohydrodynamic (EHD) flow, isotachophoresis (ITP), and electrothermal flow (ETF).
• Analysis of on-chip ESI interfaces, emitter design, buffer management, and voltage-domain separation.
• Comparison of mechanisms' strengths and limitations for low-input proteomic workflows.

Main Results:

• Electrokinetic microfluidics enables controlled transport, separation, and concentration of minute sample volumes.
• On-chip ESI interfaces are crucial for stable coupling with mass spectrometry (MS) detection.
• Various electrokinetic mechanisms offer distinct advantages for specific proteomic tasks.

Conclusions:

• The combination of electrokinetic microfluidics and on-chip ESI is a promising strategy for miniaturized, low-input proteomics.
• Technical factors governing the interface between microfluidic manipulation and MS detection are critical for stable and sensitive analysis.
• Future developments in materials, automation, and intelligent control are needed to enhance robustness and reproducibility.