Monday, February 23, 2015

Upgrading from microscope to nanoscope

There is an increasing amount of academic and industrial research and applications development around the nano-scale, and the market of nanoscope is really growing. But these systems are not cheap: the acquisition of a super-resolution system costs several hundred thousands dollars, without mentioning the cost of laboratory real estate and trained personnel.

In addition, what are the real possibilities of optical systems ( who operate with visible light in the 400nm - 800nm range) to resolve nanoscopic features in the 100 nm range ? How can "400nm photons" see features that are smaller than them ?


Sophisticated confocal microscopes can achieve excellent resolution of 250 nm to 500nm depending on their cost (in particular related to the laser system, the optics, the detector and the computing capabilities to capture and "stack" and process many images) in the X and Y dimensions. In the Z dimension, the technology has much less resolution.  The installed base of such microscope is huge, and there are many good manufacturers. Every decent life-science lab has one, plus all the surrounding accessories, trained users and all the related image analysis tools.

In this blog, we would like to show you how two manufacturers are marketing upgrades (or "add-on") systems that use very astute approaches to improve the resolution of a confocal microspcoe by a factor ot 1.5 to 2, hence reaching the ~100nm limit.

Airyscann from Zeiss
In the middle of 2014, the German company Zeiss has launched a "add-on" system that  plugs into the optical port of their confocal microscope (picture to the right).

In addition to an improved laser beam management system, the big idea in this upgrade is to use a totally new concept of detector (camera). Instead of using a full field camera to capture the signal emitted by a sample illuminated by a very narrow light source (pinhole), Zeiss has introduced a detector that has a honeycomb structure (like a bee's eye): each of the  32 channels (each element of the honeycomb detector) collects all light of an pattern simultaneously. Each detector element functions as a single, very small pinhole. Knowing the beam path and the spatial distribution of each AiryScan pattern enables a very light efficient imaging: you can now use all of the photons that your objective collected ! Further signal deconvolution and image treatment enables resolutions in the ~150nm range !

The resulting images show features with much better resolution, enabling users to investigate (basically "see") features and events that they could not see below. For "only" $150k, many new questions can be answered ! ( Another way to look at it: imagine how many new cool internships for high-school can be generated!)


This is an example of the higher (X1.5 times) resolution obtained on the Zeiss confocal microscope equipped with the Airyscann upgrade)


CODIM100 from Bioaxial
The young French company Bioaxial is addressing the same opportunity with a totally different approach. As opposed to Airyscan where the trick resides in a multiplexed detection system, the investors at Bioaxial are using the properties of bi-axial crystals to "split" the light depending on the incoming polarization of the photons.  In short, the upgrade system contains optical elements that can split and shape the laser bean before it goes through the sample. When very high voltages are applied to the bi-axial crystal, several outcomes can be controlled, and the deconvolution, addition, subtraction of the images captured on a conventional detector can resolve features that are smaller to the typical resolution of the confocal microscope.

This is well illustrated in the two figures below:




The company is not fully commercializing its product yet in the US, and we do not know the price of the upgrade, but it will have to be in the $150k range to compete with Zeiss's Aryscan unless it brings significant differentiated value ( seem they are very gentle with the substrate, and do not damage it with the lase beam).

Their images are very nice as well:


In conclusion, we see that the market for upgrades of confocal microscopes to increase their resolution ( to ~100nm- 150nm at best in X and Y) is growing with new players and very astute ideas. This systems will not replace real super-resolution nanoscopes ( ~50nm resolution) , but the ticket to acquire such upgrades ( ~$150k) is VERY attractive. I cannot wait to put my hands on one of these systems.



Monday, February 9, 2015

The Toolbox of Nanotechnology researchers

What is the "toolbox" of a nanotechnologist ? I started tobuild my own list until I found the perfect answer on the webpage of the National Science Foundation's Material Research Science and Engineering Centers (MRSECs) Shared Facilities.

The Materials Research Facilities Network is a nationwide partnership of the Shared Experimental Facilities (SEFs) supported by the MRSECs. The MRFN is designed and operated to provide support to researchers and experimental facilities engaged in the broad area of Materials Research in academic, government and industrial laboratories around the world.

Every line on this list his linked to the related center (U.S. Universities) that can provide access to such tools.


Types of equipment