MIT engineers have developed three-dimensional arrays of antibodies that could be used as sensors to diagnose diseases such as malaria or tuberculosis.
The sensors, which contain up to 100 stacked layers of antibodies, offer much more sensitivity than existing antibody-based sensors, which have only a single layer of antibodies.
“The more antibodies you put on a surface, the lower the concentration of molecules you can detect,” said Bradley Olsen, an associate professor at Massachusetts Institute of Technology (MIT) in the US.
“You can have a big impact on biosensors by potentially improving the sensitivity by several orders of magnitude,” said Olsen.
The team’s new design approach relies on a phenomenon known as self-assembly, which occurs when thermodynamic interactions drive molecular building blocks to take on certain configurations.
In this case, the researchers discovered that they could force antibodies and other proteins to form layers by attaching each protein to a polymer tail.
The proteins and polymers repel each other, so the molecules arrange themselves in a structure that minimises the interactions between the protein and polymer segments.
“Because the protein and polymer are bonded together, they can’t separate like oil and water. They can only get apart from each other by a distance about the size of one molecule,” Olsen said.
“If you do this in three dimensions, then you get things like cylinders of protein surrounded by polymer, or alternating layers of protein and polymer,” he said.
Olsen and colleagues attached each protein to a polymer chain known as a PNIPAM. When they coated a solution of these molecules onto a surface, they formed a thin film containing between 10 and 100 layers of the protein-polymer structures.
The traditional method for creating large arrays of antibodies on a surface is to chemically or physically bond them to the surface. However, this technique only creates a single layer of antibodies.
A thermodynamic principle holds that the more antibody molecules there are on a surface, the lower the concentration of molecules they can detect.
Therefore, stacking layers of antibodies on top of each other offers a way to dramatically improve the sensors’ sensitivity, researchers said.
Using their new self-assembly strategy, the researchers created three-dimensional arrays of IgG antibodies, the main type of antibodies found in human blood.
These densely packed arrays, which have the potential to be 100 times more sensitive than existing antibody sensors, also featured nanoscale channels that allow the sample to flow easily through the entire sensor.