It has been quite some time since our last blog post due to a great deal going on at BMC! Alongside some new product releases, we recently made a few adjustments and updates to our ophthalmic imaging instrument, the Adaptive Optics Scanning Laser Ophthalmoscope (AOSLO) which we are releasing early next year.
This next-generation instrument allows in vivo retinal imaging on a cellular level and is currently undergoing beta testing at the Beetham Eye Institute at Joslin Diabetes Center, led by Dr. Jennifer Sun and her team. There it is being used to directly quantify features such as cone density, microaneurysm size and measure blood flow through the microvasculature in the retina. By pairing a Scanning Laser Ophthalmoscope (SLO) with advanced Adaptive Optics, it offers the advantage of imaging the retina at a resolution 2-3 times that of a standard SLO.
The AOSLO is also capable of measuring various properties of retinal cone physiology. Due to its enhanced imaging and software, it enables evaluation of the following attributes:
- Cone Density
- Nearest Neighbor Distance
- Voronoi Tessellation Tile Area
- Effective Radius
- Packing Factor
The AOSLO’s ability to measure such features allows early stage detection of visual decline due to diabetes. This can be identified by the decrease in cone regularity, cone mosaic changes, cone reflectance and a decrease regularity of cone spacing. This function of the AOSLO can help determine early treatment plans for patients and generate further investigative studies.
When testing out the AOSLO at Joslin, we found something very interesting out about our CEO, Paul Bierden. The pictures below depict his own retina, discovering that he has a microaneurysm! This was unexpected news, since normally it would be undetectable by any other retinal imaging systems. 30% of the microaneurysms imaged using the AOSLO at Joslin were not visible in fundus photos. The AOSLO is able to accomplish this by evaluating the vascular and neural retinal planes in vivo with cell-scale resolution. The pictures below also point out the microaneurysm attributes that can be measured. They are:
- Presence of lumen clot
- Wall reflectivity
Lastly, the AOSLO is able to measure small-vessel blood flow. This is done with the help of its enhanced imaging qualities, instrument optimization and post-processing software. By stopping a horizontal scan over a blood vessel, it can measure the blood velocity by tracking the moving erythrocytes over a scanning line. With this information, researchers can produce a blood velocity profile for retinal vessels. See the video below to see how it’s done!
If you have any interest in using the AOSLO, let us know! Please give us a call and let us know about your research. We are accepting orders for the new instrument and are open to collaborative grant applications to secure funding. If you are interested in seeing the AOSLO in action, we are setting up appointments now for the next few months. We hope to hear from you soon!
In our last blog post (Fast and Precise Laser Pulse Compression with the Linear Array DM) we discussed research being done in the Cui Lab at HHMI’s Janelia Farm Research Campus that used our Linear Array DM for laser pulse compression. In part two we examine a two photon fluorescence microscopy project led by associate Reto Fiolka at Janelia Farm that illustrates the use of the Linear Array’s potential as a pulse compressor for imaging applications using the phase resolved interferometric spectral modulation (PRISM) optimization technique.
The Linear Array pulse compressor setup was used to restore the laser pulse to its transform limited state, thus improving the ability to excite fluorescence by two photon absorption. A sample consisting of 10 micron diameter fluorescence beads (emission: 465 nm) was prepared and spread on a cover-slip. The laser beam first propagated through the pulse compressor and was subsequently focused on the sample using a 20X NA 0.5 Nikon objective. A 2D image was obtained by translating a motorized sample stage. Without spectral pulse shaping, only a weak fluorescence signal could be obtained (See figures a and c). Since the objective adds significant additional dispersion to the laser pulse, the spectral phase correction that had been determined previously using the photodiode could not be used. Therefore PRISM optimization was repeated using the fluorescence signal coming from the beads itself as a feedback signal.
Janelia Farm’s results show a dramatic increase in fluorescence signal for the optimized spectral phase (see figures b and d). The signal strength was increased by a factor of ~6.5
According to Fiolka, “The tested device represents a promising alternative to liquid crystal displays, since the MEMS technology enables high filling factor, high efficiency and operation speed, exceptional phase stability and accuracy and can be used over a very broad wavelength spectrum.”
We're very excited about these results and we are currently working with other groups interested in reproducing these results on tissue samples. Thanks again to Dr. Fiolka and the Janelia Farm group for their efforts in improving two photon imaging techniques!!
More details can be found in our Linear Array white paper which includes an application overview of this exciting project. You can also link to the research directly using the links to the Cui Lab and the scientific publication above.
Ultrafast lasers have been extensively used in ground breaking research including two Nobel Prizes. Applications within spectroscopy, photochemistry, laser processing and microscopy are widespread. However, to capitalize on such short laser pulses, a pulse compressor is required to compensate for the dispersion induced by optical elements. Liquid crystal based spatial light modulators are most commonly used in laser pulse compressors. Although a proven technology in display applications, liquid crystals have drawbacks including phase jitter and a limited fill factor. Researchers at the Cui Lab at HHMI’s Janelia Farm Research Campus looked to Boston Micromachines Corporation’s prototype Linear Array Deformable Mirror (DM) to address these challenges.
To evaluate the performance of the pulse compressor, the laser pulses were analyzed with frequency resolved optical gating (FROG) using a commercial instrument (Grenouille, Swamp Optics, Atlanta, GA). In Figure a and b, the temporal and spectral profile of the pulse is shown when a flat wavefront is displayed on the DM. Evidently, the pulse is distorted and the spectral phase is not flat at all (a flat spectral phase is required for a transform limited pulse). Next, the beam returning from the pulse compressor was focused with a concave mirror onto a GaAsP photodiode and the resulting nonlinear signal was used as a feedback for the correction algorithm. After optimization using a technique called Phase resolved interferometric spectral modulation (PRISM), the temporal profile (Figure c) shows a dramatically shorter, Gaussian shaped pulse. The spectral phase is perfectly flat (Figure d) with less than 0.01 radians phase error and is stable in time. These results suggest that the precision and stability of the Linear Array DM allows close to perfect restoration of transform limited laser pulses. For more information on the optimization technique, you can access a scientific publication here.
In our next blog post, we will discuss the results of the use of the Linear Array DM in an interesting two-photon microscopy experiment.
More details can be found in our Linear Array white paper which includes a more detailed description of this application.
This past summer, Boston Micromachines Corporation conducted a survey of nearly 300 members of the business and scientific community to find out what features were valued in a deformable mirror for adaptive optics and other wavefront correction applications. Respondents came from our three major vertical markets: microscopy, astronomy and laser science. In this survey, we asked some fundamental questions and had respondents choose between three DMs with properties varying in categories of actuator count, stroke, response time and price in various combinations. We were able to drill down to what each respondent valued. Here are some of our key findings:
1) Actuator count was the most valued property
Across all verticals, this was true. Overall, respondents preferred an average of 1000 actuators. While microscopists preferred 140 actuators by almost 2 to 1 over other models, those who identified as laser scientists were looking for an average of 1001 actuators and astronomers preferred, on average, 1800 actuators.
This was very interesting to us considering we are the only player in the market to provide deformable mirrors with these actuator counts as standard products or are developing DM systems which meet these specific needs (we have a 2000 element mirror in the works).
2) High speed is important
The most frequently chosen option for response time amongst laser scientists was 50μs and all other disciplines preferred average response better than 300μs. This is great news for the industry considering that most mirror architectures can respond adequately to meet the needs of the users. Our DM architectures are available with response times up to 22μs and we are able to drive these mirrors with our X-Driver (response time down to 4μs), satisfying high speed requirements as well.
3) Low price is desired
As we hear so often, most users were looking for low-priced devices. This was the second preferred property after actuator count. While those of us in the industry talk about lower prices with higher volumes, the volumes just haven’t been there yet to make this prophecy come true. The hope in the future is that the DMs based on scalable technologies, such as MEMS, will take off and lower-priced devices will be available.
We definitely learned a lot from this survey, above and beyond what is mentioned above. If you have any questions about our methods or are interested in discussing more specifics about the responses, I would be glad to chat further. Just contact me at firstname.lastname@example.org.