Organ-on-a-chip Biosensor Mimics Human Body for Drug Development

A synthetic biosensor that mimics properties found in cell membranes and provides an electronic readout of activity could lead to a better understanding of cell biology, the development of new drugs, and the creation of sensory organs on a chip capable of detecting chemicals, similar to how noses and tongues work. A study published in the Synthetic Biology journal of the American Chemical Society describes the technology that allows the studying of body proteins in ways that would be incredibly impossible with current technology.

The bioengineering feat uses synthetic biology to recreate a cell membrane and its embedded proteins, which are gatekeepers of cellular functions. A conducting sensing platform allows for an electronic readout when a protein is activated. Being able to test if and how a molecule reacts with proteins in a cell membrane could generate a great many applications.

But embedding membrane proteins into sensors had been notoriously difficult until the study’s authors combined bioelectronic sensors with a new approach to synthesize proteins.

Proteins within cell membranes serve many important functions, including communicating with the environment, catalyzing chemical reactions, and moving compounds and ions across the membranes.

When a membrane protein receptor is activated, charged ions move across a membrane channel, triggering a function in the cell. For example, brain neurons or muscle cells fire when cues from nerves signal charged calcium-ion channels to open.

Organ-on-a-chip Biosensor Achieves the Human Avatar in Silicon

The researchers have created a biosensor that starts with a conducting polymer, which is soft and easy to work with, on top of a support that acts together as an electric circuit that is monitored by a computer. A layer of lipid (fat) molecules, which forms the membrane, lies on top of the polymer, and the proteins of interest are placed within the lipids.

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In this proof of concept, the researchers have created a cell-free platform that allowed them to synthesize a model protein directly into this artificial membrane. The system has a dual readout technology built in.

Since the components of the sensor are transparent, researchers can use optical techniques, such as engineering proteins that fluoresce when activated, which allows scientists to study the fundamentals via microscope, and observe what happens to the protein itself during a cellular process.

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Currently, researchers have used proteins grown and extracted from living cells for similar applications, but given this advance, users won’t have to grow proteins in cells and then harvest and embed them in the membrane platform. Instead, they can synthesize them directly from DNA, the basic template for proteins.

Coming of Age of organ-on-a-chip Technology

With such a system, a drug chemist interested in a particular protein implicated in disease might flow potentially therapeutic molecules across that protein to see how it responds. Or a scientist looking to create an environmental sensor could place on the platform a particular protein that is sensitive to a chemical or pollutant.

Researchers may now take the proteins that are activated when we smell something and translate the results into this electronic system to sense things that might be undetectable with a chemical sensor.



Source-Eurekalert