Micro-Physiological Systems for COVID19

The National Institute of Health (NIH) recognized the dire need for efficient testing of vaccines and treatments for COVID19 during the beginning of the pandemic. In April 2020, the NIH announced an SBIR grant for the use of micro-physiological systems (MPS). MPS tools simulate the human physiology for studies of toxicity and efficacy of compounds that may be used to prevent or treat diseases. Several commercial models can be found on our marketplace here!

One of the major reasons the process of vaccine development typically takes between 10 and 15 years is due to the length of clinical tests for vaccines. [2] The process of testing the safety and efficiacy of a treatment or a vaccine to prevent the spread of COVID-19 are being done on patients. This is a very risky and inefficient process in the biomedical world. For many reasons, testing in model systems that replicate physiology would be much better.

PerfusionPal from Lena Biosciences

There are few micro-physiological systems available commercially, and few of those can apply to this challenge. One of the suitable platforms is PerfusionPal from Lena BiosciencesPerfusionPal is a system that perfuses 3D tissues, oxygenating them efficiently. The ingenious principle behind the technology is fluorocarbon fluid. Fluorocarbon fluid has a much greater capacity to carry oxygen than water, and the fluid is completely immiscible. The fluid acts as a flexible and sterile piston. The fluorocarbon fluid drives media solutions through the porous inserts holding the cells, delivering nutrience throughout the 3D tissue.

This system can be used to grow tissue for days with minimal attendance in high-throughput on 12- or 48-well plates. This may be applied to COVID19 studies because lung cells express the ACE2 receptor. SARS-CoV-2 uses ACE2 to gain entry to cells in both lower and upper respiratory tracts. PerfusionPal from Lena Biosciences may help researchers study the infection and create better models of the infected system in the lungs.
 

The substitute blood fluorocarbon fluid has a very interesting property which could be of interest for researchers studying respiratory infections such as COVID19. The flurocarbon fluid is breathable; it can be breathed like amniotic fluid in the womb. Therefore, animals that breath air are able to breathe fluorocarbon fluid - This is called liquid ventiliation. Since the fluid is heavy, it descends through the lungs to open the areas of atelectasis and could potentially help people breathe. The use of fluorocarbon fluid would also reduce the possibility of the COVID-19 infection spreading through the lungs. These techniques are used to save neonates (under-term babies with under-developed lungs), so there is a possibility that this technique could have an impact on COVID-19 respiratory failure. [3,4]


Another area of interest in the impact of COVID-19 on human neurology or the nervous system. There is strong evidence that suggests SARS-CoV-2 has neuro-invasiveness aspects. [5] Many scientists believe that greater efforts should be directed to study the neurological complications that are products of patients with COVID-19. In many COVID-19 patients, it is clear that the human body's nerve cells clearly have a tropism (an innate response to the virus) within their nerve cells. This would include testing the receptors that are being used for the virus to gain entry to nerve cells in humans. 
 
In summary MPS are enabling tools that are able to test toxic or ineffective medicines on people who need them most. The goal of using MPS in the drug development life cycle is to create a process with higher throughput that uses miniaturized and efficient microfluidics platforms rather than animal or 2D models.

References

1. “NOT-TR-20-017: Notice of Special Interest (NOSI) Regarding the Availability of Emergency Competitive Revisions to Existing NIH Grants and Cooperative Agreements for Tissue Chips Research on the 2019 Novel Coronavirus.” National Institutes of Health, U.S. Department of Health and Human Services, grants.nih.gov/grants/guide/notice-files/NOT-TR-20-017.html. 
2. Han, Seunghoon. “Clinical Vaccine Development.” US National Library of Medicine National Institutes of Health, Jan. 2015, pp. 46–53., doi:10.7774/cevr.2015.4.1.46. 
3. The Children's Hospital of Philadelphia. “Neonatal Liquid Ventilation.” Children's Hospital of Philadelphia, The Children's Hospital of Philadelphia, 7 Mar. 2018, www.chop.edu/research/neonatal-liquid-ventilation. 
4. UpToDate, www.uptodate.com/contents/liquid-ventilation. 
5. Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. 2020 Jun;92(6):552-555. doi: 10.1002/jmv.25728. Epub 2020 Mar 11. PMID: 32104915; PMCID: PMC7228394.