Wyss Institute Researchers Take Aim at Replicating the Immune System Onto a Chip

March 30, 2022 by Darshil Patel

Meshing together bioengineering with electronics, Wyss Institute researchers developed a microfluidic organ-on-a-chip (OoC) to mimic human immune functions and study the efficacy of vaccines on a chip.

The world of electrical engineering continues to overlap with other disciplines, especially as technology continues to adapt and evolve. One area attempting to blend electrical engineering with medicine is bioelectronic engineering. 

With that in mind, a recent technology, the Organ-on-a-Chip, has the potential to model complex body disorders by realizing different organ functions on a chip. 


A high-level timeline of OoC technology evolution.

A high-level timeline of OoC technology evolution. Image used courtesy of Cherry Biotech Innovation


Capitalizing on this type of technology, researchers from the Wyss Institute for Biologically Inspired Engineering at Harvard University have used microchip manufacturing methods to create microfluidics culture devices that mimic human organs' complex structures and functions. 

Before delving into their research, it's important to overview what OoC technology is and what technology is actually involved.


A Brief Overview of Organ-on-a-Chip

Generally speaking, an OoC is an integrated circuit that simulates the operations and responses of a body organ. In other words, it is a type of artificial organ.

Currently, OoC technology can mimic various organs, including the liver, kidney, and brain tissues. It aims to accelerate drug development and reduce animal testing. Moreover, the technology also promises to overcome the limitation of high drug failure rates in testing systems like animal models. 

Talking about implementation, the OoCs are made using fabrication techniques from the chip manufacturing industry. As chip fabrication technologies evolve rapidly, there is increasing attention toward implementing OoCs.

These microdevices generally consist of a clear, flexible polymer that contains microfluidic channels lined with human organ cells and blood vessel cells. These channels are 10 to 100 micrometers in size but have a large surface area and high mass transfer, allowing the observer to understand the effects of drugs on them.


An example OoC from Wyss Institute.

An example OoC from Wyss Institute. Image used courtesy of the Wyss Institute


At the center of their research, the researcher's cultured human cells responsible for building the immune system into the microfluidic channels for studying cellular-level activities when exposed to some foreign molecule.


Realizing Organ-on-a-Chip

An OoC generally consists of three major components: 

  • Microfluidics
  • Cell tissues
  • Sensing mechanisms 

The target cells are delivered at a location using microfluidics through its system for fluid input and discharge. 

The cell tissues are components that align a particular cell in a 2D or 3D shape. For 3D arrangements, biocompatible hydrogels help to prevent damage. The sensing mechanisms can help detect and compile the data, and it can be an embedded system or a transparent system for visual evaluation. 

For transparent chips, various imaging techniques can be helpful to assess the cellular-level activity. The embedded systems use biosensors for monitoring models with metabolic activities, barrier functions, and electromechanical properties. 


Example uses of OoC technology.

Example uses of OoC technology. Image used courtesy of Wyss Institute


Biosensors can be used to measure electrical activities in the nervous system. Multi-electrode arrays (MEAs) are helpful in such cases as neurons grow in a densely packed, highly organized, and 3D environment.

However, building artificial organs requires precise cellular manipulation. What's more, a detailed understanding of the organ's responses and characteristics is critical. 

Another limitation is that OoCs need special complex instruments for achieving reliable results.

Dr. Yu Shrike Zhang, Instructor of Medicine and Associate Bioengineer at Harvard, states that a significant challenge for this technology is replicating the complexity of human organs and tissues in vitro, minimizing it, and then linking them within a system to act like the desired organ. 


Developing an Immune System on a Chip

The researchers at the Wyss Institute at Harvard University have cultured human B- and T-cells inside a microfluidic OoC, also known as an LF (lymphoid follicle) chip, to probe the function of the immune system

Human B-cells produce antibodies that attack foreign viruses and bacteria, and T-cells are responsible for destroying the cells that are infected by viruses or are cancerous. 


Image of (a) structure of the LF chip and (b) Cultured B- and T-cells that form 3D structures when flowing.

Image of (a) structure of the LF chip and (b) Cultured B- and T-cells that form 3D structures when flowing. Image used courtesy of the Wyss Institute


These cells are cultured inside different chambers, which helps researchers to observe the cascade of events occurring when these cells are exposed to an antigen. They claim that these LF chips can also predict the response to various vaccines. 

Dr. Girija Goyal, a Senior Staff Scientist at the Wyss Institute, mentions that the shift away from using animals as research models for developing bioengineered technology is necessary. This shift is necessary because animals can have a different immune response than humans and thus yields inaccuracy. 

Goyal believes that their LF Chip can provide a way to model the complex human immune responses to infection and vaccination.

Overall, the LF chip consists of two parallel microfluidic channels separated by a microporous membrane, and the B- and T-lymphocytes are isolated in these channels. 

When the researchers started the medium flow through the other channel, they observed B- and T-cells self-organize into 3D structures within the chip, similar to structures where complex immune reactions occur. They found the production of various chemicals and enzymes responsible for immunity in the human body.


Future of Organ-on-a-Chip Technology

The human body's immune system is obviously very complicated. With that in mind, science still lacks accurate answers to some of the important questions regarding the immune system and its ability to protect the human body. 

Thankfully, the researchers now have a potential new tool to replicate the immune functions and vaccine responses on a chip.

Further development in OoC fabrication techniques could allow more complex biological functions to be modeled with high accuracy and reliability. It will be interesting to see how the fields of bioengineering and electronics continue to work together.