Approach 1. Sub-channel for Smaller Droplets that are INVISIBLE
ESI performance is improved by generating Initial charged droplets (ICD) with smaller sizes. Traditionally this have been achieved by using smaller emitter tip opening, which encounters practical problems (clogging) when entering the nanoscale.
Our new approach is to create small (nanoscale) dynamic meniscus inside large (micrometer-scale) tip opening. In the above case, low flow rates (50 pL/min) and extremely small droplets (invisible) were produced using a micron-sized emitter tip. These small droplets (estimated to be 16 nm in diameter) have avoided the formation of most NaCl salt cluster ions. (READ MORE)
But, what is the lowest limit for ESI flow rate and droplet size? Hope our research will help to answer these questions.
Our new approach is to create small (nanoscale) dynamic meniscus inside large (micrometer-scale) tip opening. In the above case, low flow rates (50 pL/min) and extremely small droplets (invisible) were produced using a micron-sized emitter tip. These small droplets (estimated to be 16 nm in diameter) have avoided the formation of most NaCl salt cluster ions. (READ MORE)
But, what is the lowest limit for ESI flow rate and droplet size? Hope our research will help to answer these questions.
Approach 2. Native Protein Charge States without Buffering Agent
Proteins exhibit distinct charge states, non-specific adducts, etc. that are sensitive to ESI conditions. We are using model protein standards to investigate the charged droplets produced under novel ESI conditions.
Left spectra show that the femtoamp mode (fA) ESI generates native protein charge states without any buffering agent. This indicates the charged droplets produced in the fA ESI are significantly different than those produced by regular nanoESI. (READ MORE) The methods and knowledge gained in this type of research are also applied in the analysis of manufactured protein products, such as the mAbs and glycan samples in collaboration with industry partners. |
Approach 3. Ionization Current and Flow Rate in Femto Units
Ionization current and sample consumption rate are two fundamental characteristics of an ion source. We are developing methods to measure flow rates and ionization current down to the femto range!
In 2021, we have discovered the femtoampere ionization. This has set the record of lowest ionization current for electrospray ionization, which is conventionally known to have onset current in the nanoamp (nA) range. This also demonstrates, for the first time, an ionization current that is lower than what the MS detectors can handle.(READ the IJMS Article) In 2022, we reported the measurement of femto flow (240 fL/min) electrospray ionization. Using flow rate and ionization current, an equation was derived to calculate the size of nanoscale initial charged droplet. MS signal suggest flow rate as low as 16 fL/min and initial droplet as small as 34 nm. (READ the Analyst Article) We expect these dim ion beams to have a bright future in addressing some of the decade long challenges in mass spectrometry. |
Approach 4. Ionization Efficiency to be Tamed
Taming ions is a romanticized description of mass spectromists' endeavors. Ionization efficiency is one of the least tamed and least understood behavior of ions. Non-uniform ionization efficiency is also one huge limitation in quantitative mass spectrometry. We are exploring experimental parameters that may lead to new understandings or solutions for this problem.
In a recent published work, data from ~3000 scans (on the left) show a trend to equal responses (100%±10%) for maltoheptaose and neurotensin when using pico flow sub-channel ESI. A trend toward more uniform ionization was also observed for a peptide mixture, (READ MORE). At this point, methods developed in my group are producing 1-2 orders of magnitude more charged droplets than the number of analytes. We are investigating the physics and chemistry that may ensure the ionization of each and every analyte. |
Approach 5. Charge and Chemistry on the Surface
We investigate the behaviors of charge on surfaces. In collaboration with the Zi group at CUHK, we realized adjustment and polarity inversion of triboelectric charge by external electric field. For Kapton, one insulating material, surface charge density was controlled from -600 to 600 μC/m2. (READ MORE)
The maximum charge density is equivalent to +-0.1% monolayer (10E15/cm-2). In comparison, a 100 nm water droplet at Rayleigh limit has a surface charge density of ~0.4% monolayer. |