Mouse Specifics, Inc
Millions of mice and rats are used annually by academic researchers, biotechnology
companies, and the pharmaceutical industry in studying human diseases and developing
new drugs. The electrocardiogram (ECG) is a key index of the health status of
the animal. The ECG not only reflects cardiovascular performance, but can also
be used to diagnose numerous other conditions, including disease of the central
nervous system, the endocrine system, and metabolic disturbances. In drug development,
moreover, the ECG is widely used to indicate potential toxicities of new therapies.
ECGs in mice and rats are frequently studied to address questions regarding the
ECG in humans, because of their small size, comparable heart morphology, and
genetic similarities to humans. Mouse Specifics, Inc. (MSI) is a Boston-based
company that develops laboratory instrumentation to study mice and rats. Recognizing
the need for improved technologies to record ECGs in conscious mice and rats,
MSI developed non-invasively technology to detect the electrocardiograms passively
through the paws of the animals. MSI needed an electrode configuration to meet
its specifications, which included animal welfare, high signal strength, noise
immunity, and reliability. MSI contacted BioDetek.
MSI had determined that the lead plate had to meet several criteria, the most
important of which was high conductivity and good noise rejection. Since the
animals are conscious and moving, signal artifact from the animals’ motion can
confound interpretation of the signal. The size and spacing of the electrodes
needed to accommodate a wide range of animal sizes, including neonatal mice and
large rats. Since animals urinate and defecate, the design needed to accommodate
this inevitability without compromising the integrity or longevity of the electrodes.
The materials used needed to be safe and non-toxic in case of accidental ingestion
by the animal, and the tactile interface between the electrodes and the animal’s
paws should not irritate the animal.
The development of any new product requires both an understanding of the customer’s need and an understanding of the technology involved in solving the customer’s problem. Bio-Detek initially chose product designs that utilized existing materials. As we, both the customer and Bio-Detek, developed a better understanding of the unique characteristics of monitoring a mouse’s ecg and the shortcomings of our initial designs, creative thinking and new materials were used to define improvements. Through iteration and experimentation, a final solution was defined that met customer requirements and took into consideration manufacturing issues including cost and packaging.
Bio-Detek used a wide variety of tools to deliver the final product. All drawings
were done in SolidWorks and extensive testing was done in-house to ensure that
AAMI standards, which admittedly were written for human ECG and not for mouse
ECG, were being met.
Mouse Specifics, Inc. was granted a patent on its non-invasive technology and approach to recording electrocardiograms in conscious animals. Although the technology is now widely used to record ECGs in mice and rats, the technology is scalable to record ECGs in larger mammals, including guinea pigs, dogs, and humans. Mouse Specifics has granted Bio-Detek exclusivity in providing the “foot-plates” to MSI and its customers. The methodology has been described in nearly 20 publications, including studies of mouse models of heart failure, lysosomal storage disease, and HIV. A study of the ECG in a mouse model of Duchenne’s muscular dystrophy (DMD) has led to the development of a new diagnostic test for infants with DMD and possibly to a therapeutic approach to their cardiovascular complications. Over 10,000 ECGs have now been recorded via the MSI technology, now dubbed “The ECGenie”, and BioDetek continues to provide the electrodes for such experimental and preclinical studies.