As the largest generation in history enters their senior years, research into muscle pathologies has come into greater focus. These can include rare conditions like muscular dystrophy or more commonly, muscle atrophy due to cancer or disuse after injury. To develop drugs and therapies that combat this broad group of myopathies, functional measurements of muscle are often required in animal models. Aurora Scientific has worked with researchers in this community to provide tools that allow the study of muscles like the diaphragm as well as non-invasive assays to perform longitudinal tests on an individual animal as a disease or therapy progresses. We are proud of our long history working with the leading researchers and academics in this field and proud of the role our muscle pathology research instruments have played.
Muscle Atrophy Through Disease, Disuse or Chronic Injury
Duchenne muscular dystrophy (DMD), cachexia & sarcopenia, gerontology & aging, muscle atrophy, Spinal Muscular Atrophy (SMA), myotonia, glycogen storage disease type II (Pompe Disease), myotubular myopathy
Dr. Leo Ferreira – University of Florida
The equipment and customer support I have received from Aurora Scientific is amazing. Their engineers and software developers have spent countless hours tailoring protocols, software, and apparatuses to meet my needs. Their support and assistance have strengthened my research tremendously. I consider my relationship with Aurora Scientific to be a true partnership.
Dr. Coen Ottenheijm – Vrie Universitet
Several Aurora Scientific systems are in use in my lab. Their equipment has allowed us to generate precise, publishable data for many years. Their local support team has a good relationship with my lab workers, allowing us to resolve issues quickly and with a minimum of disruption. I consider them to be a valued collaborator in our work.
1200A – Easy To Use System Is an Invaluable Tool for Lab
In 2013 Aurora Scientific was approached by Dr. Espen Spangenburg at the University of Maryland about our 1200A test system for working with isolated EDL and soleus muscle taken from mice.
Dr. Spangenburg studied the mechanisms of muscle metabolism and intended to make use of in-vitro techniques to perform his research. While Dr. Spangenburg was familiar with these types of experiments from his work with similar home-built equipment used in graduate school, he needed something easy to use and reliable for his own lab.
Though the system was essentially a standard configuration, the 1200A proved that it is an easy to use, turnkey system for measuring mechanics of intact excised muscle. Aurora Scientific provided Dr. Spangenburg with a robust, accurate system that was capable of being configured to fit his specific needs. The system was engineered to include an adjustable tissue bath and mounts to simplify experimental setup. In addition, we included our flagship Dual-Mode muscle lever, enabling the control of both force and length for a gamut of experimental protocols. Aurora Scientific provided further technical support to Dr. Spangenburg’s students covering software use and best practices for using the system.
Dr. Spangenburg was easily able to set up and configure the equipment to his lab’s needs and obtained high quality contractile data immediately with the first muscle tested using the system. The ability to adjust the tissue bath and mounts to suit their needs provided an avenue for straightforward tissue attachment and Lo measurement for accurate and reproducible experimentation. Control and measurement of force and length allowed the lab to go beyond isometric measurement to test more complex muscle mechanics, such as eccentric and concentric contractions. The test system proved to be easy to use by both professor and student alike and was used by the lab for several subsequent studies. The 1200A enabled them to expand their research, resulting in a number of publications, and remains an essential piece of equipment for the lab to date.
1300A – 3-in-1 Test System Helps Major Pharmaceutical Companies Dramatically Improve Throughput
Several large Fortune 500 pharmaceutical companies sought a way to quickly screen large groups of mice that had been treated with new experimental compounds/therapies.
Existing equipment in house was either unavailable or difficult to use and lacked the capabilities needed to meet throughput demands. The precision of any in house equipment was also questionable.
With the 1300A 3-in-1 system, Aurora Scientific provides researchers with a cost effective alternative, enabling quick, easy measurement of intact and isolated muscle function. Designed for in-vivo, in-vitro and in-situ testing, the 3-in-1 system is ideally suited for experimental protocols which require quick transitions between configurations. Combined with the ability to assess aggregate skeletal muscle function without surgery, sample throughput is further enhanced and scientists are able to meet the testing demands of large animal colonies. The system’s high throughput analysis module continues to improve productivity following experiments by providing batch processing of a large number of data files in seconds.
Researchers at these pharmaceutical companies saw immediate benefit from using the 1300A 3-in-1 test system, in some cases testing up to 50 mice per day and limiting the number sacrificed. Switching between the in-vitro and in-situ configurations when necessary, took only a few minutes, saving the researchers time and money, which allowed them to re-invest from their budget into additional systems, further improving throughput. The high precision system permitted small but significant therapeutic changes to be resolved and potentially used in life saving human medication. Furthermore, batch processing provided time saving analysis, enabling researchers to quickly formulate conclusions. Their work led to the publication of many studies which were presented at major international conferences. The system itself played a significant role in allowing drug DPU’s at major pharmaceutical companies to meet their goals and targets.
1305A – Footplate Configuration for Rats Invaluable to the Study of Muscle Damage
In 2012, Marius Locke at the University of Toronto had been studying skeletal muscle damage and the role that heat shock proteins (HSPs) play in protecting the muscle from stress-induced damage, such as exercise.
Dr. Locke was looking for equipment that could reliably and repeatedly induce muscle damage in his rats while accurately quantifying force production and recovery.
Our 1305A system was suggested for the job as it had the ability to perform the kinds of repeated contractions that Dr. Locke was looking to accomplish. It was first implemented piecemeal to integrate with some existing equipment in the laboratory, but because of its ease of use, the remaining Aurora Scientific pieces were added for a complete system. Aurora Scientific technical support helped craft the best protocols for Dr. Locke’s experiments and soon thereafter the first cohort of rats was tested.
The system has helped Dr. Locke and his graduate students publish valuable findings about the protective role of HSPs in damaged muscle. In addition, Dr. Locke established an important rat model of standard human exercise protocols to gain valuable, physiologically relevant data which may one day be applicable to athletes and people alike.
1310A – A Custom Apparatus for Larger Animal Models
In 2011 Aurora Scientific was approached by Dr. Christopher Cardozo at the VA Medical Center to assist with researching the mechanisms of muscle atrophy in rats.
Dr. Cardozo planned to use in-situ methodology to test certain muscles of interest; however, his rat model was very large and he expected that they would produce large forces. Aurora Scientific’s existing 1305A system and 806D platform could .accommodate the measurement of forces up to 10N, which the animals were expected to well exceed. Larger transducers existed but they were too big to fit on the existing 806D.
Aurora Scientific had recently redesigned most of their in-situ apparatus and had spent a great deal of R&D time on building large animal apparatus. As a result, Aurora Scientific had the experience and expertise to design a solution that would meet the needs of Dr. Cardozo and deliver at an affordable price. A new apparatus was designed, more robust and easily able to withstand the higher forces and loads of large animals, yet still compatible with existing clamps and accessories for small animal use.
The Aurora Scientific solution worked well in Dr. Cardozo’s lab and provided an easy way for him to measure muscle force in large animals. He was able to collect large amounts of useful experimental data. The unit would later go on to find a minor niche for in-situ testing in lizards and also squirrels and other less conventional animal models. The redesign ultimately became the centerpiece of our 1310A Complete System.
1400A – Durable System Helps Researcher Study Thousands of Fibers
In 2004, Dr. Hans Degens was studying changes in skeletal muscle function and morphology. Dr. Degens was looking to use permeabilized fibers as his test samples as they represent a pure system for studying cross-bridge mechanics without bias and artifacts.
Dr. Degens was familiar with the experimental methodology of using skinned fibers but lacked the resources to build a system from scratch that could handle the higher throughput demands of testing human samples.
Aurora Scientific had recently released the 1400A system. This system featured an automatically indexing chamber enabling maximization of fiber throughput. The design also eliminated any manual bath movement, commonly found in designs at the time, thereby protecting the sensitive transducer from breakage. Dr. Degens’ system was also the first to feature peltier driven temperature control, allowing for extremely stable and precise bath temperatures, critical to these measurements. The powerful 600A digital controller has allowed for nearly every experimental protocol conceived to be executed by the instruments themselves.
The system has been in nearly constant use in Dr Degens’ lab for the last 11 years and has helped him collect data required for many influential and fascinating studies in exercise physiology, comparative biology and cardiovascular health amongst countless others. This initial partnership with Aurora Scientific has led to other projects in whole muscle physiology as well.
300C Series Custom Modification Facilitates Genetic Therapy Research for Rare Myopathies
A group of researchers in North Carolina had several colonies of specially bred dogs as a model for muscular dystrophy and other rare myopathic disorders.
To test experimental therapies and learn about the disease progression, the researchers required an instrument to test whole animal muscle function. The researchers had used the Aurora Scientific 300C series for other applications previously and approached us about a special in-vivo modification for our largest model in the series, the 310C-LR. Although similar modifications had been made for other models in the series, the sheer size of the animals and the modifications required posed a number of engineering challenges. The first prototypes caused vibrations to appear on the signal and rendered the instrument effectively useless.
After a number of conventional prototypes made from aluminum failed to perform consistently, and with deadlines looming, the R&D team at Aurora Scientific needed to design an unconventional prototype quickly. To lighten the mass of the modified lever, and to make it stiffer and stronger, a carbon fiber material was used on a conventional aluminum holder. Materials were sourced from a local aerospace company with a long history of using carbon fiber material on rockets. The first prototypes were machined and shipped to the laboratory in time to perform mechanics experiments. Aurora Scientific engineers were on site in the lab to assist with initial testing and measurements.
The carbon fiber prototype proved to work successfully and the vibration was eliminated. This allowed the researchers to perform all the measurements required for testing the muscle function of their specially bred animals. These researchers and many of their collaborators have successfully utilized our custom equipment for nearly eight years, facilitating the characterization of disease progression, advancement of life saving research and enabling promising therapies to reach FDA approval. The design has since been refined and become a standard Aurora Scientific product, which has provided researchers studying other large animals such as pigs, sheep and monkeys the ability to characterize muscle mechanics in-vivo.
300C – Dual-Mode Muscle Lever Enables Myonecrosis Research in Injured Muscle
Dr. Cliff Bayer has been studying myonecrosis induced by Group A streptococci (GAS) bacteria at V.A. Medical Center in Boise Idaho. Interestingly, this necrotizing infection develops in sites of muscle injury and is thought to be exacerbated by anti-inflammatory drugs (NSAIDs).
Dr. Bayer was interested in assessing the role of NSAIDs in this process, but had no reliable or reproducible way of inducing hindlimb eccentric injury in mice to test this mechanism. Furthermore, this process needed to be performed in-vivo as injection of GAS needed to be done 48h post-injury.
Dr. Bayer consulted with Aurora Scientific about his needs. We determined that our 300C Dual-Mode Muscle Lever would be an ideal solution. The 300C has the unique ability to control and measure length and force in a reliable and precise fashion. This was crucial as Dr. Bayer needed to lengthen the muscle repeatedly during stimulation while simultaneous measuring force to induce sufficient muscle injury prior to injecting GAS. In addition, Aurora Scientific’s footplate design permitted in-vivo hindlimb testing that was crucial to his studies.
The dual-mode lever allowed Dr. Bayer to perform reliable and reproducible eccentric injury in murine hindlimb muscle. Furthermore, the footplate attachment allowed him to perform in-vivo experiments increasing throughput and permitting injection of GAS 48h post-injury. This led to numerous publications describing the mechanisms involved in necrotizing infections following muscle injury and more effective treatments to replace use of NSAIDs. Dr. Bayer has successfully utilized this motor for nearly a decade and has recently integrated Aurora Scientific’s 1300A 3-in-1 muscle test system along with peripheral equipment and software to further his research.
400A – Studying cancer cachexia in mouse models
In 2011 Dr. Theresa Guise and her colleague Dr. Andrew Marks approached Aurora Scientific seeking help in functionally characterizing muscle from their mouse tumor model. They were looking to assess the progression of muscle loss and weakness in these mice and investigate potential therapies.
Because the pathology in these mice was incredibly aggressive, many animals would need to be tested in a short period of time. This would necessitate the use of multiple rigs and a robust transducer that allowed for high throughput. Because Dr. Guise was only looking to perform basic isometric strength and fatigue measures, a dual-mode lever system would have been prohibitively expensive for its capabilities.
Enter the Aurora Scientific 407A. As the transducer in the 400A series with the greatest force measurement capacity, it was suitable for making isometric force measurements in whole skeletal muscle from mouse. The unit is the most robust out of the whole 400A series, lessening the risk of accidental damage. The 407A was effectively paired with a modified 800A in-vitro muscle apparatus, as well as our 701C electrical stimulator and 615A DMC/DMA software.
The 407A transducer helped the labs of Dr. Guise and Dr. Marks to test many mouse models of cancer cachexia and performed so well that several more units were required in both labs to keep up with demand. Using the Aurora Scientific 407A, these researchers were ultimately able to determine the mechanisms and pathways that cause muscle weakness associated with various cancers. These results and many others were recently published in Nature Medicine.
900B – Sarcomere Length in Zebrafish Larvae
In 2011 Dr. Dennis Claflin approached us to try out our 900B Video Sarcomere Length system. Dr. Claflin was a long time user of Aurora Scientific equipment and an expert in single fiber measurements. He had been using a simple laser diffraction method to quantify SL in his permeabilized fibers, however, this method was not compatible with another one of his chambers.
This chamber would be mounted on an inverted microscope and used to test the mechanical forces of single, living zebrafish larvae. Because of their relative ease of rearing and their transparent body, these larvae can be used as an inexpensive model for a variety of human myopathies.
Since our 900B Video Sarcomere Length system uses a c-mount camera, it is compatible with virtually all inverted microscopes. Additionally, there are no complicated procedures for calibration of different tissues. A simple reticule to correlate camera pixels to distance and 5 minute calibration was all that was required. As long as the sample presents a remotely visible sarcomere pattern the software would converge to the dominant solution. All of these attributes made the 900B the right choice to study zebrafish larvae.
The video sarcomere length system was put to work on a variety of different tissues such as lumbrical muscle and ultimately zebrafish. The camera proved quite successful for setting resting SL in the zebrafish larvae despite the overlapping of tissue and skin. The lab’s results using these methods have been extensively published and were recently featured in a JoVE video publication.