Ion sources are the unsung heroes of mass spectrometry. They do more than create ions, they set the limits on sample throughput, automation potential, and data quality. Ionization is simply turning a neutral sample (the analyte) into charged particles (ions) so the mass spectrometer (MS) can measure them. Whether your platform is a tightly integrated LC-MS, an automated sample processing system, or a manual interface, the ion source is the first and often decisive point of contact between your sample and the mass analyzer.

The principal and chief engineer of ZEDion, Josh Zarecky, has designed 5 distinct ion source products over the last 13 years. The developed instruments included several variations to interface with different mass spectrometers and supported ESI, PSI, LESA and APCI applications. In addition to those ground up developments Josh contributed to design improvements to the DESI platform prior to Waters acquisition in 2019. We build custom ion sources to meet real-world constraints: variable solvents, high-duty cycles, tight footprints, and seamless interactions or integrations with autosamplers, fluidic systems and other automation modules.

Ionization Technologies

Selecting an ion‑source format locks in more than ionization physics. Solvent limits, voltage parameters, maintenance considerations, and even licensing fees all cascade from this choice. The table below compares established and emerging atmospheric/ambient sources, highlighting where they excel and the integration pitfalls most often cited in recent literature and vendor notes.

Core Design Considerations

Once the ion‑source type is chosen, a different layer of engineering begins. Materials must survive aggressive solvents; flow paths must avoid dead‑volume precipitation; high‑voltage traces require dielectric clearance; heaters must hold temperature without leaking heat into neighboring electronics. Below are some considerations our team understands and evaluates during concept reviews and throughout the development process.

Materials

When developing an ion source every aspect of the design has critical characteristics and the one characteristic that transcends all elements of design is materials. A mass spectrometer is basically the world’s most sensitive nose. If you put something in front of it that has a chemical signature it will smell it.

Polymers

PEEK and PTFE are staples in MS applications. Any other plastic anywhere near the MS inlet can contribute to background noise due to outgassing, especially if exposed to solvent.

Metals

Any metals in the sample / solvent path must be stainless steel, ideally 316L for optimal corrosion resistance and minimal risk of contamination. Aluminum is great for base structures but should not come anywhere near the sample.

Ceramics

In high heat applications, especially over 300C, where even PEEK approaches its glass transition temperature, ceramics are king. Ceramics offer superior thermal stability, can handle extreme temperatures and provide excellent insulation for the rest of the system. However, they are expensive and require careful design for machining and consideration to the application when specifying the type of ceramic.

Fluidics

There are generally two forms of fluids used in three ways. Liquids that carry or extract an analyte and gasses that assist ionization. Interfacing with external fluid systems or integrating fluidic systems within an ion source it is important to consider the source, flow path and delivery scheme.

Source

Solvents should be HPLC grade or better, almost without exception. Similarly, gasses, most commonly N₂ are delivered from a tank or dewar and should be extremely high (99.9%) purity. Additional pure zero grade air can be used to shield the ionization interface from the ambient environment which can contribute to background noise.

Flow Path

The flow path, primarily referring here to liquid solvents, is perhaps the most critical sub-system of an ion source. The level of concern varies with application. When delivering pure solvents materials are your primary concern. PTFE is the go-to for tubing and PEEK or stainless steel for fittings. When the flow path also contains sample which may contain salts especially when working with tissue the flow path should also have near zero dead volume to prevent carryover between samples. Salts can also precipitate out of solution and cause clogging in the system especially in ESI emitters which are usually polyamide coated fused silica and can have internal diameters under 50 µm in some applications.

Delivery Scheme

Gas flow is often regulated to a specific pressure and/or flow rate. In the case of DESI as a nebulizing gas nitrogen is regulated to between 100psi and 180psi and flows at a rate of <1L/min to ~2L/min. In some applications, like LESA, the gas flow is actually used to drive solvent flow carrying analyte from the extraction interface via a venturi effect at the ESI interface where the analyte is introduced into the mass spectrometer.

Most use cases incorporate a positive displacement pump to drive liquid solvent flow through the system. As is common in most analytical applications smooth pulse free flow with exceptional rate and volume resolution is paramount which is what makes syringe pumps the ideal choice. However, in some applications like PSI where solvent is used for both sample re-wetting and elution the critical performance characteristic is discrete dispensing of small aliquots of solvent in the 10µL to 50 µL per dispense range. For those applications I have seen success with both rotary piston and positive displacement solenoid pumps.

High Voltage

High voltage (HV) is the mechanism by which an analyte is ionized when aerosolized hence electrospray ionization (ESI) and is commonly supplied by a high voltage power supply integrated into the mass spectrometer. The integrated HV supply is intended for use with the native MS ion source. Aftermarket ion sources need to connect to the MS high voltage interface, usually adjacent to the inlet where the ion source would mount and then connect to where the HV is needed within their source. Alternatively, some sources may use their own internal HV supply.

High voltage for MS typically ranges in the 3kV DC to 8kV DC range. Fortunately, the peak current is in the µA range. It won’t kill you, most likely, but doesn’t feel good and is very much considered hazardous. When working with high voltages you need to consider creepage (distance across a surface energy can travel) and clearance (distance through air energy can travel) for adequate insulation / isolation at levels most electrical engineers who focus on PCB design have never even considered. Material characteristics like dielectric strength, pollution degree and surface tracking index factors into the design. The best thing to do is pick up a copy of IEC 61010 – Safety Requirements for Electrical Equipment for Measurement, Control and Laboratory Use. Specifically get to know section 6 – Protection Against Electric Shock and the associated insulation tables in the appendices.

Thermal Control

There are two factors to consider for thermal control. First is the interface to the mass spectrometer. The inlet interface is heated usually to around 300ºC. You need to be aware for your own safety but also you don’t want to directly touch it with your ion source which will conduct heat away from the inlet and into your device unnecessarily.

Second and more relevant to ion source design is thermal control of heaters within the ion source, if any. Most ion source applications run under ambient conditions and have no need for a heater. The ones that do use a heater need to get hot (300ºC to 500º) and stay there with minimal fluctuations. At temperatures above 300ºC polymers melt and metals will conduct heat where you want it and everywhere you don’t too. Ceramics are your friend and enemy. They work great but cost a lot, are difficult to machine and are extremely notch sensitive so they fracture and break easily. Once the physical design is sorted an excellent PID loop is needed to maintain the temperature within a narrow range of +/- 2% or less ideally. Changes in temperature can have an immediate and direct impact on ionization efficiency resulting in broadening peaks or total loss of signal. In some applications where the heated portion of the system is more like an oven with more significant hysteresis a PID loop can be difficult to tune, and I have seen success with bang bang control, but the result is not as stable and less ideal.

One last note on thermal controls regarding heaters and temperature sensors. Assuming you are running in the 300ºC plus range I recommend cartridge heaters or custom ceramic heating elements and RTD temperature sensors. For ion source applications you are less concerned about response time because the goal is to hold a constant temperature and an RTD offers long term stability and highly linear response not common in thermocouples or thermistors.

Contamination & Service

The nature of high end analytical and life science instruments is they need to be cleaned and maintained to continue to function as a high-end instrument, Common ion source maintenance and service intervals range from per sample and daily to quarterly, annual and as needed. A good rule of thumb would be anything that needs service more frequently than once a quarter should be designed to be completed without the use of tools. Emitters and tubing are easy wear items and standard chromatography fitting make this easy.

Contamination and carryover are the invisible killers of good data. One preventative design element to be included on fluid-based systems that carry analyte in a solvent is having some valving and a rinse routine to flush the sample path between samples to prevent or at least minimize carryover. Some samples are extremely sticky, and some applications require tubing or other components be replaced for each sample.

The other element to consider is the MS inlet capillary. Most ion sources use the inlet capillary supplied with the MS. Others have a custom inlet capillary. While a tool may be needed it is important to plan for the eventuality that this needs to be removed and cleaned or replaced with variable frequency depending on the samples being analyzed.

Manufacturing & Modularity

When you move from concept to production, the goal is to make every new ion-source behave exactly like the last one. Take it off for cleaning, put it back on, and the spray lands in the same place without a calibration dance. The key to good design for manufacturing and assembly (DFMA) is good drawing practices. Define the critical surfaces and datums that control alignment but keep tolerances realistic so any competent CNC shop can hit them without exotic tooling. Build in locating features like pins or keyed flanges so the components self-align. A technician should never need to “dial it in by eye.”

Modularity is an art in and of itself. Facilitating changes between operating models like ESI / APCI without a completely different source increases the potential use cases for your ion source. Similarly, when it comes to overall system architecture a good modular design mindset means that sub systems are swappable and revisable without cascading impacts to the rest of the system. This is great for R&D and long-term support.

Automation Hooks

Controls are often an afterthought in the grand scheme of hybrid instrument development. That doesn’t really make sense considering one of the core elements of hybrid instrumentation, like an ion source is automated and integrated controls, yet it happens, likely because without the hardware what controls are there to develop.

We know that good design plans the entire architecture, hardware and controls, from the beginning. This is especially important for ion source development. The interface to the mass spectrometer has multiple electrical and IO connections for source ID, type of ion source, high voltage, ready and trigger signals, power for heaters and other ancillary systems, and interlocks.

1. Beyond that there can be APIs and SDKs to directly interface with the MS control software or peripheral device connections for coordinating the MS and ion source workflows.

Proprietary Interface Hurdles

This is the real kicker to ion source development…Most commercial spectrometers lock source geometry and firmware to their own ecosystem. If you plan to retrofit or design a drop‑in source, budget for hidden barriers. The major MS instrument manufacturers include: Thermo Fisher, Waters, SCIEX, Bruker, Agilent, Shimadzu etc. They all have their own proprietary interfaces, and the details of the interface specifications are not publicly available. You need to have connections, sign NDAs and have a little luck in your back pocket to get details and CAD is even harder to come by. If you are fortunate, like I have been, you develop an ion source in collaboration with the major manufacturers and have at a minimum skeleton CAD depicting key mounting interfaces on the MS and some documentation to fill in the gaps. If not expect to spend a lot of time in the lab reverse engineering the interface before you can design a new ion source. Even with all the data every use case is different and there are challenges to overcome, and modifications needed to accommodate the application to ensure a robust and reliable connection to the MS.

Key Questions Before You Commit

Clarifying these six points early prevents months of redesign:

1. Chemistry: What’s the toughest solvent or buffer you’ll use, and will the sample carry grit or salt that can clog tiny lines?
2. Speed: How many samples per hour or is it a steady flow? Design tolerance jumps between batch work and continuous duty.
3. Control signals: Does the source just need an ON/OFF line, or must it change voltage or flow on command from a robot or PC?
4. Mass-spec model: Triple-quad, QTOF, Orbitrap—each has its own limits on pressure and ion current.
5. Service plan: Will users pop in a pre-aligned cartridge or call a tech for a bench rebuild?
6. Vendor data: Do you have the OEM drawings and pin-outs, or will you be figuring them out yourself?

Lock these answers in writing first to save weeks or months of rework later.

ZEDion Development Workflow

Our multidisciplinary roadmap reduces risk and calendar time:

1. Scope + Regulations – Define user needs, target markets and design requirements, then map them to IEC 61010, ISO 9001/13485, CE and other applicable standards. Even if your end goal is research use only (RUO) depending on target market and the application regulations apply and we want you to be ready.
2. Architecture Development – Lay out system in diagram form. Define the liquid path, gas lines, and high-voltage route; pick standard parts where they fit; rough in high level design to align vision and goals
3. Preliminary Design – Do the heavy lifting and factor in all the details needed to get from concept to first pass functional prototype. This is an iterative and collaborative process.
4. Bench Prototype – Assemble a working prototype, wire heaters and sensors, and capture first test data. Focus is function, not finish. Learn, iterate, refine, repeat.
5. Design Freeze – Tighten the model for real machining, add test points, call out traceable materials, and lock the tolerance stack.
6. Pilot Lot – Build a small run with the final processes, run safety-and-performance checks, and update the risk file, drawings, and user docs.
7. Release Package – Deliver the full BOM, drawings, QC plan, test reports, and a ready-to-submit regulatory dossier. Manufacturing can start without another engineering pass.

Want to further accelerate development and derisk your project? Ask us about the FlexRail modular embedded control platform and how it can be leveraged for your ion source or hybrid instrumentation development project.

Ready to Talk Ion Sources?

If you have an idea for a novel ion source product or your current source is blocking automation or limiting sensitivity, let’s architect one that fits your workflow, no compromises.

Book a complimentary design consult → HERE 

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*** Images shown depict ion sources we are permitted to show designed by Josh / ZEDion over the last 13 years ***

References

[1] FossilIonTech nano‑ESI overview (2024)

[2] National MagLab: APCI technique note (2023)

[3] National Library or Medicine: Current Scenario and Challenges Using MALDI TOF MS (2021)

[4] Journal for the American Society of Mass Spectrometry: Deconstructing DESI (2012)

[5] International Journal of Mass Spectrometry: Paper‑spray substrate/solvent study (2021).

[6] JEOL USA: DART Applications Notebook, Rev. EN002 (2023)

[7] International Journal of Mass Spectrometry: LESA for Native MS (2017)

[8] Analytical Science Journals: Ion Chemistry in DBDI (2024)