humanizing animal studies with less invasive microsampling methods

Gathering important data in general preclinical research and pharmaceutical research for drug development and discovery often requires testing on living organisms and cells, or in vivo. Some data simply can't be gathered via tests on dead organisms or tissue.

Animal studies allow scientists to conduct investigations that aren't possible in humans or to develop drugs that need to be tested before administering in humans to ensure they are safe. Many scientific studies rely on animal research for good data, but quality of life for research animals has long been a concern. In recent years, researchers have sought methods that reduce the discomfort or stress that research animals may experience.

Animal research methods typically involve collecting blood from one animal frequently, sometimes as many as 2-4 times in a day at different time points. Frequent blood sampling can cause smaller research animals, such as mice and rats, to be depleted of too much blood, leading to diminished health or early death.

A principle called the 3Rs of animal research has provided a structured and ethical way for scientists to use less invasive sampling methods in their animal studies. This principle is intended to reduce the negative impact of testing on animals.

The concept of creating a principle for more humane treatment of research animals originated with Charles Hume and others at the Universities Federation for Animal Welfare (UFAW) in the 1950s. This principle was formally launched in the early 1960s by biologists William Russell and Rex Burch, who published a book outlining a process for animal research that advocated for:

1. Replacement alternatives – Seeking other ways to perform experiments without using animals. It explains the molecular level research performed using in vitro samples.
2. Reduction alternatives – The book recommends reducing the number of animals used during animal testing. Scientists are encouraged to use past data to estimate the number of animals they need for research.
3. Refinement options – Researchers are encouraged to reduce stress associated with traditional blood sampling methods.

The 3Rs principle has led to using certain microsampling blood collection methods to make animal studies more humane. Microsampling techniques involve the use of smaller sample volumes to assess chemical and drug exposure in the plasma, blood, or serum. Since the microsamples are less than 50 µl, the smaller sample volume has a reduced impact on the animals' health, and a less invasive collection process is less stressful for the animals.

How Microsampling Works

Improvements in molecular analysis have led to the development of a range of microsampling techniques, including dried blood spot (DBS) cards, plasma microsampling, and volumetric absorptive microsampling (VAMS^®).

Volumetric absorptive microsampling is a novel approach that allows researchers to collect a very small, but precise volume of capillary blood on the absorptive tip of a specimen collection device called a Mitra^® microsampler. The blood dries on the Mitra^® tips after collection. In the lab, the blood samples on the tips are processed and analyzed as dried blood samples. VAMS technology has been found to more consistently deliver the correct sample volume needed for analysis over some other microsampling methods, such as DBS cards. 

Achieving the "3Rs" with Mitra Microsampling 

The Mitra device collects small drops of blood from animals at 2-4 time points. The collection process involves using a small lancet to prick the animal and gather the drop of blood on the absorbent tips. The amount of blood drawn with this method is significantly reduced, increasing the animal survival rate. The samples are dried, stored, and transported for analysis, an advantage not possible with traditional blood collection methods.

The goal of the 3Rs of animal research and similar ethical guidelines for the United States, European Union, and other countries is to require scientists to abide by humane principles that ensure greater quality of life for animals used in research studies. More advanced and minimally invasive microsampling technologies, such as the Mitra microsampler, make it possible for researchers to achieve that goal.