Longer description of your proposed project

End stage renal failure means that you are no longer an organism that can get rid of its own waste. You, as a human, feel robbed from your dignity, dependent on machines and external connections to sustain your life, at a much reduced quality. You constantly fear the loss of your capabilities to provide for your partner, your family and to be there for them. Such is the nature of this illness. And in the rest of the developing world, dialysis is sometimes altogether unaffordable, condemning those with ESRD to death. Current dialysis technologies haven’t changed much, owing in part due to the vested interests of pharmaceutical companies in propagating the currently very lucrative status quo that equates to $50B per year, which is about 10% of Medicare spending. And in others due to then yet needed advances in membrane science.

I want to create a technology that will once and for all end the suffering of dialysis patients and reduce the costs associated with treating end-stage renal disease. Most costs incurred in this are those of the consumables, which includes very large quantities of pure water, dialysate, energy as well as dialysis clinics (medical centers), nursing and other such care. I want to do this in the form of an implantable bio-artificial kidney.

As you might have read my comments online. I first thought a biological solution was more in order, and more permanent. I still believe this. But the time horizon is uncertain, and a lot of effort is being spent already in organoid technology from all sorts of institutions for all sorts of diseases. Progress in one, will naturally lead to progress in others. But this technology is uncertain, when it will come to fruition is also very uncertain. It still relies on a lot of fundamental research. It may come to be that, we really need the embryological niche for artificial organ development, which can stopper the progress if not technologically certainly legislatively.

I therefore wish to pursue this hybrid route of artificial blood filtration membranes and kidney cells seeded on artificial membranes. I think here we have a lot less exotic research to do, but more applied research, merging technologies that are more mature.

One of the challenges I currently face is getting enough blood to filter through the artificial membranes. The pores of the membranes need to be very small, around 7nm, this is to block albumin leaking freely in to the filtrate. These small pores have a lot of resistance to flow. To get adequate filtration, we are still 3 orders of magnitude away. Each membrane (currently from silicon, but I am working to synthesize titanium dioxide nanotubes in Tu Delft) yields 40 ul/min filtration rate. To end dialysis we need 10 ml/min, ideally 30 ml/min (GFR equivalent). If I can increase the pore size by a factor of 2, I can decrease the resistance to flow by a factor of 16. This is due to hydraulic resistance decreasing as a fourth pore of pore radius, which is huge! But I must do this without albumin leakage. Albumin is negatively charges. The glomerular basement membrane in the healthy kidney is also negatively charged, so repels albumin. I want to emulate this by applying a small negative charge (think pacemaker kind of charge) to my membrane, be it silicone or titanium dioxide. I can make these conductive by applying thin metal coating in grid-like fashion in the case of silicon, or leave thin titanium support fins for the titanium oxide (which is synthesized by anodizing titanium foil). This would keep my pores large, and hence allow good filtration whilst allowing for albumin rejection.

All in all, this would mean that I need to pack less membranes in to my implantable device and also have less surface area for fouling and thrombosis of the device. I see this technology as an essential piece of the puzzle to get the form factor of the kidney, to a heart driven implantable artificial kidney, otherwise things really become hard when we try to get the same filtration from an artificial device.

Describe why you think you're qualified to work on this

I don’t have references or citations in this field yet. But I feel that the most important thing to succeed is a good motivation and aptitude. I have much of the former, and I hope I will show that I have the latter. My supervisor and everyone involved with my hiring in University Medical Centre Utrecht took a huge risk in hiring me. Someone that wasn’t in the field, if I messed up, they’d had to answer. But thankfully so far, they are happy. I have forged a relationship with my collaborators at TU Delft, who also seem to be happy. So other people have believed in me, and so far, I have not let them down. And I am certain that I won’t. Because for me, this is not a pursuit of a life in academia. Rather, I want to make sure that I don’t have to hold my children with a catheter attached to my belly ever again. I am really after this device that will set me and others like me, free, nothing else. If I find in 5 years time, that such a device is infeasible, I will set my eyes on another approach. And I will loudly proclaim it such so that not a single cent is spent anymore on it.

Aside from my motivation. I am a mechanical engineer with a PhD from TU Delft. I did some notable work in my previous field, and besides this I find that my current work is very multidisciplinary. So far I have designed and milled the microfluidic flow cell where the membranes are tested. I have built the sensorisation for pressure, for flow and the amplification circuits as well as the code. I will start the electrochemical etching of my own titanium dioxide membranes in January. These should be stronger than the current silicon ones and have higher porosity. I have a master-student that I am co-designing the blood filtration part of the implantable kidney. Here we are looking at how we might pack as many membranes in to the device as possible. I have also built some computational models regarding strength and clearance of these membranes. I don't think there are many persons that from the start could be competent in all these areas.

Overall, I do lack any formal qualifications, aside my mechanical engineering masters, in this area. But I feel like in a short time, I have shown myself to be competent in the hands on work also.

Other ways I can learn about you

I have my themotte account, I am sharing this in hopes that it will not discourage you. It mainly details my dialysis journey

https://www.themotte.org/@Panem

And here is my ACX handle

https://substack.com/profile/176926287-tugrul-irmak

How much money do you need?

$80,000 I am currently fairly alone in this work. I want to work with a fellow post-doc. I will not supervise the post-doc but really work beside them. My aim is to produce the metallic coating/fins and the testing setup (flow cell) and the post-doc to test how to charge it, perhaps model how the coating/fins should be i.e. the spacing between them etc. 80,000 would be enough funds for 1 year of post-doc salary according to the regulations for scientific personal in the Netherlands and I think the project can conclude in 1 year. One thing I don’t like about the post-doc contracts is that they are usually short, so offer little long terms stability. But our group is currently applying for other grants which should hopefully extend this, if he/she choses to stay.

Links to any supporting documents or information

No response.

Estimate your probability of succeeding if you get the amount of money you asked for

0.8 I think the method is novel, but feasible. We are emulating the kidney, and there the charge selective barrier does have a large effect.

Success is defined as, acceptable albumin leakage at pore size of 14-20nm diameter. Where acceptable leakage would be 1-2g per day (this is still on the high side, but I don't expect it to be too clinically relevant as long as the device overall works well).