Body-on-a-chip technology has many names, it is also called human-on-a-chip technology or a microphysiological system.
Image Credit: Nature.com
Fundamentally, it is a network of miniature in vitro organs that link together to create bodily systems. To date, many different systems have been made including, a lung-heart-liver model, an ovary-fallopian tube-uterus-cervix-liver model, and a cardiac-liver-neuron-skeletal muscle model.
These body-on-a-chip models are used for pharmacokinetics as they provide cheap high-throughput models that are carefully designed to replicate a bodily system.
As these models use human tissues, they have greater accuracy over traditional animal models while increasing the possibility for personalized medicine, where the tissues could be derived from patient stem cells.
How does it work
The body-on-a-chip systems are composed of multiple different organ-on-a-chip models that are linked together. Each organ-on-a-chip is the size of a memory stick and is specially designed to recreate an organ analogous to its in vivo counterpart. All this is accomplished using a combination of structure, microfluidics, and stem cells.
Previously, in vitro tissues have struggled to maintain function because of the reliance on diffusion to supply nutrients to the cells. Consequently, the organ-on-a-chip models use microfluidics to supply nutrients, this is more efficient and realistic providing both shear stress on the cells and a medium through which signaling molecules can travel.
By providing an environment that has greater fidelity to the in vivo environment it creates an organ with morphology similar to its in vivo counterpart.
The exact structure of each organ-on-a-chip depends on the organ’s function. However, there are commonalties across organ chips. Each organ is encased by an outer structure, within this there is are two microtubes separated by a porous membrane on which the tissue has been grown.
On one side, the microtube supplies the microfluid, whereas the contents of the other microtube depend on the organ’s function. In the lung-on-a-chip, this second tube was made to mimic air whereas in the intestine-on-a-chip it represented the gut lumen.
To create the organ tissues, the appropriate stem cells are carefully selected. These stem cells can either be multipotent or induced to pluripotency, these are guided to differentiate to form the desired tissues.
Additionally, tissue stress is an important factor to ensure the correct tissue morphology. The lung tissue was placed under periodic strain, simulating the expansion and contraction of tissue, replicating the act of breathing.
From organ-on-a-chip to body-on-a-chip
Moving from a single organ-on-a-chip to a body-on-a-chip introduces greater complexity. Firstly, the system has to be linked together. For this there are two major methods, using a micropump or a pumpless gravity-driven system.
The micropump allows for precise control over the microfluid and its constituents but there is the risk of air bubbles whereas a pumpless gravity-driven system reduces the control over the microfluid but creates a self-contained environment.
Another major consideration is how to scale the system to faithfully recreate the in vivo environment. In allometric scaling the scaling is based on organ size or tissue density, in contrast, residence-time scaling is based on the amount of time the blood spends in each organ.
The advantage of body-on-a-chip technology is that it is high through-put miniaturization. This miniaturization reduces the number of materials needed to make and keep the system running. These materials have to be carefully considered; materials used to make the device may interact with drugs thereby distorting the results.
Consequently, efforts have to be made to ensure that the construction materials are inert. On the other hand, body-on-a-chip technology uses human cells which confers a greater accuracy on pharmacokinetics. This use of human tissues rather than animal tissues reduces erroneous results thus accelerating drug discovery and reducing attrition.
In drug development, organs-on-a-chip have been suggested for use in the early stages of drug development and body-on-a-chip models for latter stages. These body-on-a-chip uses could include checking for side-effects in other organs or working out the dosage.
These systems could also be used in personalized medicine if combined with induced pluripotent stem cells. By creating a body-on-a-chip from patient stem cells, the efficiency of the drug, side-effects, and appropriate dosage could be observed before treatment.
There are applications beyond pharmacokinetics, with a functional neuromuscular junction being developed to study motor neuron diseases. Body-on-a-chip technology could also be used to measure different exposures either, chemical exposure, food ingredients, or cosmetics.
Body-on-a-chip technology produces bodily system models that can be easily used to test pharmacokinetics. A body-on-a-chip provides a contained environment where chemical effects on human tissue can be easily studied, as such, it is providing innovation in drug discovery that can speed up the discovery of new drugs.
However, the downside is that each organ has to be designed, grown, and combined in a functioning system. Each of these steps initially requires time and effort. Once these steps have been achieved, then it provides a good basis for testing how chemicals interact with the body.
However, most body-on-a-chip systems only contain a few organs and therefore these systems do not yet have the complexity of in vivo systems.
- Abaci, H. E. and Shuler, M. L. (2015) ‘Human-on-a-chip design strategies and principles for physiologically based pharmocokinetics/pharmacodynamics modeling’, Integrative Biology, 7(4), pp. 383–391. doi: doi:10.1039/c4ib00292j.
- van Duinen, V. et al. (2015) ‘Microfluidic 3D cell culture: From tools to tissue models’, Current Opinion in Biotechnology. Elsevier Ltd, 35, pp. 118–126. doi: 10.1016/j.copbio.2015.05.002.
- Kimura, H., Sakai, Y. and Fujii, T. (2018) ‘Organ/body-on-a-chip based on microfluidic technology for drug discovery’, Drug Metabolism and Pharmacokinetics. Elsevier Ltd, 33(1), pp. 43–48. doi: 10.1016/j.dmpk.2017.11.003.
- Shrestha, J. et al. (2019) ‘A rapidly prototyped lung-on-a-chip model using 3D-printed molds’, Organs-on-a-Chip. Elsevier Ltd, 1, pp. 1–11. doi: 10.1016/j.ooc.2020.100001.
- Sontheimer-Phelps, A. et al. (2020) ‘Human Colon-on-a-Chip Enables Continuous In Vitro Analysis of Colon Mucus Layer Accumulation and Physiology’, Cellular and Molecular Gastroenterology and Hepatology, 9(3), pp. 507-526
- Sung, J. H. et al. (2019) ‘Recent advances in body-on-a-chip systems’, Analytical Chemistry, 91(1), pp. 330–351. doi: 10.1021/acs.analchem.8b05293.