I have gotten a couple of misfires over the last 4 months on cylinders 1 (twice) and 4 (once). Codes were the misfire codes (p0301) and I also got P050B (cold start ignition timing) at the same time. On all 3 scenarios I replaced the spark plug and the problem went away. Since cylinder 1 came back a second time I just ordered a new coil pack to replace the old one. Unlike you, I have NOT replaced my manifold yet as I have not seen a reason. I have a 2010 e350 with 138k miles. Runs great. Only other thing I see is that my LTFT are running lean about +25 to +35%. So not sure if that is connected to the misfires.

There you go: LTFT+30 ... great job gathering data - Your repair will soon be done:
Your ignition is fine but fuel is not

Next you'll want to read the fuel rail pressure and tank pump pressure. Low pressure forces lean supply.

At 138kMi... you can have a plugged up dirty fuel filter and if GDI in addition also a worned out HPFP.

Thanks - I actually put in a new fuel filter about 3 weeks ago for 2 reasons: 1) it was 15 years old which is the recommended replacement by MB (non-GDI) 2) with the hopes of fixing the LTFT problem. I also replaced my fuel pump about a year ago. I am started to think vacuum leak somewhere

I got reminded recently that our MAP engines don't care about vacuum leaks the way MAF do.

You are dealing with non-GDI, new tank filter and new pump with an +30 rich trim on a lean engine.

the parts you've replaced were overdue

The only question is what's going on then ?
Read the ECU fuel rail sensor with a scanner**.

The next possible big leaker at 138kMi is the PCV at the rear of bank1. "A lot of air calling for a lot of gas"

** MB Fuel sensors do go bad.

I replaced the oil separator cover and the oil drip pan Jan 2025. Plus I did the expansion plugs. I have an Innova 5512 scanner - what would I be looking for on the fuel rail sensor? - thank you very much

The fuel rail sensor pressure readout needs to hold nearly steady pressure under load.

Non GDI in-tank pump: 60Psi
(GDI secondary pump: 2800Psi)

These values are available in the ECU module live data.

If you see pressure is significantly low or collapses... that's bad.

@RWagz Any updates? Have you had a chance to swap that ECU with a cloned version?

Thank you - according to my scanner my fuel pressure is at 55 psi consistently (Non-GDI) under load.

that proves perfect fuel rail pressure.

Based on all the prior roll up... this is aiming towards an injector issue which may be a bad ECU output MOSFET. Any chance you can listen to your injectors?

We're not talking new injectors until we're sure they are getting pulses with low spray output.

You can't really measure high-frequency pulses to get a significant number but for our purpose here: you can rule out good/bad ECU output using AC (limited to near 60Hz range).
There may be a bad +12V power source fuse (ECU switches the Gnd side circuit)

thanks again - I am really not sure what to listen for. For the power source fuse, where can I locate that?

one might guess in the fusebox the so called SAM, located under the hood on the driver side.

This thread freaked me out - last weekend in about two hours, maybe two and a half I put a new top end on one of my cars. Other than having to reset the throttle, and forgetting the cable to the MAS....smooth as can be (not to rub salt in a wound). I think that something more was going on before the new air intake system was put on.