We've all been at the point where you keep working on a project and not getting the results that you want, so you keep trying. With more and more chemicals available all the time, (and more literature to read too), it's pretty tough to completely run out of ideas and call it quits. If you ever do throw in the towel, there will always be that nagging thought that if you had just given it one more try, it might have worked out. Or worse yet, if someone else had come along, they might have tried something that we overlooked. [*]
But I managed to find a true "deader than a vampire with a silver stake in it's heart" solution to one such nagging project last week.
For reasons that will remain largely unnamed, I was trying to use UV light to crosslink a protein with the hope of achieving a certain rheological result. After trying endless amounts of photosensitive chemicals and failing to achieve what I wanted, I was starting to get the feelings I stated above: is this ever going to work and how would I know when to stop. Then it hit me: go for the acid test; go for the throat; let's pin this guy to the mat and see if it still can get up.
Glutaraldehyde is well known for crosslinking proteins with a vengeance.
It's fast (enough), effective and has been used since the '50s for this purpose. And now you might see where I was going: I used glutaraldehyde to crosslink the protein. At that point, I still didn't see the rheology results I wanted, so I knew that there was no hope from the UV approach.
Why didn't I used glutaraldehyde in the first place? Well it is a rather dangerous material to untrained personnel. It doesn't really care whether the protein is dead or alive, so proper handling of the chemical is essential, and that's why I never used it in the first place - our client was just not set up to handle such a material. Adding UV crosslinking agents (and crosslinking them) is different - the chemicals are a much lower health risk and UV lights can be effectively shielded against with minimal PPE and training.
So in the end, I got the result I wanted; well, not really. I would have loved to see the project succeed, but in this case, I could confidently walk away from it and know that it would never work - and I have the proof I needed. That is something all to rare in this profession.
[*] We certainly have plenty of clients who have said "we tried that approach and it didn't work". I love hearing that, as what it really means is that "we tried whatever we could think of and it didn't work". And it is amazing how many times we (Aspen research) can get it to work.