KidneyX Innovation Accelerator Interview 1

Kidney News interviewed Christian Schafmeister, PhD, Department of Chemistry, College of Science and Technology, Temple University, about his KidneyX Prize, “Atomically Precise Membranes for High-Flux and Selective Removal of Blood Toxins” during hemodialysis. Schafmeister presented the work for the Phase I Redesign Dialysis Prize at the inaugural KidneyX Summit in Washington, DC, on April 29, 2019.

You learned about the KidneyX Prize through a nontraditional route. Please describe it.

I was looking for applications where small, atomically precise membranes—a few hundred square centimeters—with very high selectivity and flux could be valuable. I was talking with a group developing a home hemodialysis system about applications of our membranes to dialysis, and was doing some research and wrote a white paper. I then spoke with my colleague Avner Ronen and asked if there was a need for better dialysis membranes and he told me about the KidneyX Prize contest, which was closing the next day. So, I sent in the white paper I had been writing.

How did your work with macromolecules and membranes lead you to look at potential solutions to dialysis?

We are creating large molecules with programmable shapes and looking for applications. These molecules can reach the size of small proteins. Proteins can do amazing things and we hope to develop similar capabilities but in a more “designable” way. There are a class of proteins called “membrane proteins” that act as channels to allow useful molecules to pass in and out of cells. I have thought about making artificial membrane channels for many years.

Your aim is to replicate kidney function by creating chemically synthesized, atomically precise membranes as thin as a single molecule to better replicate the selective membranes in human cells. How does your approach accomplish this?

The thinner a membrane is, the higher the flux will be because there is less resistance for small molecules that pass through the membrane. If channels are constructed that have pores about the size of the molecules and ions we want to pass through the membrane, then the pores will selectively pass their target molecules and nothing else. This is exactly what the membrane channels in the cells in our kidneys (and all cells) do. Very roughly, the kidney is a tube. At the top of the tube, everything in your blood less than about 60 kilodaltons enters the tube. As this fluid (pre-urine) passes down the tube, water, salts, glucose and some other small molecules are drawn back into the blood by highly selective membrane channels. If we can mimic what membrane proteins do, then we can replicate the most sophisticated function of the kidney, which is to pull back from the pre-urine those components that were thrown out in the glomerular capsule.

Please tell us about the “molecular Lego” approach your lab has developed over the past 15 years.

We have designed molecular building blocks that are small rings (molecular Lego bricks). These rings carry two pairs of groups (two amino-acid groups). Each of these amino-acid groups can connect through two bonds to another amino-acid group on another building block. This lets us assemble ladder molecules made up of fused rings. To each building block we can attach other chemical groups that can do things when they are brought together on the ladder backbone. We can assemble short segments and then link those together to create complex three-dimensional structures with enormous control over their shape and what they do.

What is your ultimate goal, and what are the next steps?

We are developing a variety of applications for these molecular Legos. For filtration, we are working to create membranes made out of molecular Lego nanostructures that separate molecules and ions from each other. The ultimate goal is to create membranes that can pull specific small molecules and ions out of mixtures. We are also developing catalysts, molecular Lego nanostructures that build other molecules. This would let us create valuable feedstock molecules in a more environmentally friendly way.

How can the KidneyX partnership between ASN and the US Department of Health and Human Services better encourage and capture the interest of innovators beyond the kidney space?

I don’t think a pool of innovators exist that can mimic kidney functions beyond what we have today, without new technologies that let you build things that look like biological membrane channels and integrate them into macroscopic objects. Why? The kidney carries out its most important function at the molecular scale. It must filter large molecules and cells from small molecules without damaging them in the glomerular capsule and then it must pull back valuable molecules from the pre-urine in the tubules. This is as opposed to an organ like the heart—that to a simple approximation is a pump for blood. Wearable dialysis machines, internal artificial kidneys, and home hemodialysis—all of these approaches require better liquid treatment technologies that I believe have to be engineered from the molecules up.

The best way to capture innovators is to engage people, and to ensure funding is available.

June 2019 (Vol. 11, Number 6)