Combined instruments - The future's here

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Wouldn't it be great if you had another way to analyse your sample without the need to move it to a different instrument?

Hello friends. Sort of following on from my previous posts which looked at what can happen if you're bold enough to tinker with an older microscope, I've a few thoughts to share on a recent observation. As an analytical scientist there is nothing more frustrating than not having the right technique available when you need it. I'm sure you can identify with what I'm saying from personal experience. You prepare a sample for a particular analysis and then realise that you could benefit from another (or more than one) type of analysis technique. Wouldn't it be great if you had another way to analyse your sample without the need to move it to a different instrument? This especially true for the microscopist, who may be looking at a unique, tiny site just a micrometer or less in size, that could be impossible to locate on another instrument.

I’m sure that you are aware in recent years there has been a focus on correlative microscopy that is linking the two major worlds of electron and light microscopy. However, what I’m talking about is the second revolution, which is linking two techniques (or more) to provide multiple analysis modes in the same instrument. What I’m saying isn’t new, since I’d bet that some of you have previously done some other sort of multitechnique microscopy such as confocal-Raman or SEM-EDS. What instrument manufacturers (perhaps inspired by users) have realised is that there is a real demand for new instruments that provide more than one type of information, that hasn’t been thought of before.

From an EM point of view, the trend is not new, as many of us are familiar with elemental analysis (EDS/WDS) that can relate spatial distribution of the atoms to an acquired image. Recently I noticed an advert for a 5-in-1 detector and it got me thinking that between accessories manufacturers (you know who they are) and dedicated developers of fusion techniques that things are on the up!

One of the many Tricorders used in the StarTrek series, image from of Memory Alpha

So what’s not to like? As human beings, we’ve always been keen to do more with less and develop machines to perform multiple tasks, so this seems to be little different. Taking inspiration from science fiction (specifically Star Trek) we need look no further than the Tricorder, a device which was able provide detailed analytical information in just a few scans (in most cases). If this proved ‘inconclusive Captain’, and further work was required on the Enterprise it wasn’t long before the secrets of whatever it was would end up splashed onto the wall of the science bay, no doubt courtesy of a different multianalytical instrument. In looking for an image of a tricorder, I discovered that there is actually a Tricorder Project to design a multidiagnostic device.

Although I digress, I think my point is still valid; it is more convenient to have multiple analysis techniques on one instrument. This is not only a practical analytical point, but also an administrative one. As we move to multiuser, multidiscipline centres/units and facilities, in which space may be at a premium and running costs a defining factor, the hybrid instrument makes sense yet again.

So let’s take a look at some of these new kids on the block. I know some of these will be familiar, as I’ve mentioned them before, but this issue has got me so excited I just had to throw them in, in case you missed them before. They all serve to unite two or more analysis modes in the same instrument, thereby saving time, being very convenient and what’s especially powerful is to add value to the sometimes greyscale images the EM provides. High resolution is great, but often one grey blob looks like all the rest. What’s on offer here is a little more information about what makes the blob different to the rest! 

Images from an AFM tip, with Raman signal form the same area, courtesy of HybriScan

The one area that caught my attention recently was the combination of Raman and SEM. To my knowledge there are three options, the first is RISE microscopy (Raman imaging and scanning electron microscopy), which is displayed on a Tescan instrument in the link highlighted. The second comes from Renishaw and seems to be called Structural Chemical Analyser (SCA) and it seems this can be added to any microscope (SEM of FIB). The third offering is from HybriScan who offer a convenient bolt-on to fit SEM or FIB instruments.  

RISE Microscopy: SEM and colour-coded Raman images of a diorite sample overlaid (top). Raman Image: 100 µm x 100 µm, 300 x 300 pixels = 90,000 spectra, integration time: 34 ms/spectrum. Corresponding Raman spectra (bottom): Each spectrum displays a molecular component of the sample. Courtesy of Tescan and WITec

Continuing with Raman-based methods, you may be interested to hear about AFM-Raman from Renishaw or Bruker. Both (there may be others) allow the acquisition of both AFM and Raman information with the precision of AFM but chemical mapping of Raman.

LV-SEM5 from Delong – In my post on desktop microscopes, I mentioned this, but I’m so impressed with the concept of four microscopes in one (TEM, SEM, STEM and AFM), that I couldn’t leave it out in this post. The whole system is a desktop, houses a field-emission source and runs at only 5 kV!

SECOM – Two worlds collide in this modification to the SEM, by replacing the door and equipping the stage with an optical microscope. Now you get the combination of fluorescence and SEM. The recently released i-Corr is FEI’s combo of TEM and fluorescence. These are being used today to advance correlative light and electron microscopy (CLEM).

CLEM: Localization of diacylglycerol using GFP in ultrathin sections using combined  fluorescence and EM (scale bar 25 µm). From Peddie et al., Ultramicroscopy, 2014.

FIB-TOF-SIMS – This combines a FIB-SEB with a mass spectrometer (secondary ion mass spectrometer) to allow the chemistry of surfaces to be analysed as the FIB removes material. I’m not sure what uptake has been like for this, but I’d definitely give it a go against EDS analysis as I know that SIMS is very sensitive to chemistries.

JEOL JASM 6200 Clairscope – This instrument offers a solution for those interested in correlative imaging and houses a confocal fluorescence microscope and an inverted SEM column. Samples are prepared on a special slide that has a SiN window, thus allowing the SEM to view the same features as the light microscope. Pretty neat!

I’m 100% sure that these are not the only combined instruments that are available and this was not meant to be a list of them, more a flavour for what’s happening and where we’re going (also maybe where we’ve been already). Hope to see you back here soon!

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