Organs-on-a-Chip (Synthetic Biology)... Devices to Replace Animal Testing.
   Donald Ingber (Wyss Institute Biological Engineering at Harvard) being frustrated with animal model in clinical research set out to create in vitro models using processes to manufacture computer microchips, which could maintain a surface topology at nanometer resolution. The chips have hollow channels the size of a cell and using microfluidics would allow one to manipulate processes at a cellular level.
     In 2005 they were able to to create channels small enough to simulate a small lung airway that, when liquids flowed through the channels, recreated fluid sounds akin to a physicians stethoscope. (a Lung-on-a-Chip).
Lung chip
     By 2010 (Science DOI: 10.1126/science.118830) they were able to incorporate cells creating a chip-tissue interface to monitor responses of live cells to different microfluidic drugs of chemicals (the Lung Chip). The Lung-on-a-Chip contains a vascular channel through which a blood-mimicking medium flows (red) and airway channels through which air flows (blue), each lined by living human cells. Connecting the chip to a pump can imitate the physical forces that breathing exerts on lung tissue.
     In 2021 Ingebr's group created a CF-chip. The Cystic Fibrosis AIrway Chip shows higher cilliary activity and enhanced bacterial growth in mucus (greater than seen in “healthy lung chips”), including the presence of the pathogen Pseudomas aeruginosa, which causes CF lung infections. The CF Airway Chip replicates at CF patient’s micro environment and its pathophysiology that may lead to better treatments and even cures? JCF (2021)
     Ingber’s laboratory has a $37 mil grant from DARPA to develop up to 10 different human organ chip models including, Lymphoid Follicle Chip to asses human vaccination responses and a Lung Aleveolus Chip to identify drugs that might be repurposed to treat Covid-19. DARPA announced it was seeking a system incorporating 10 organ chips that could be used to evaluate medical countermeasures, such as those for exposure to chemical or biological weapons, for which human trials would be impractical or unethical.
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