MEMS based Renal Replacement System (Artificial Kidney)

Goutam Rana Roll No: 124070011 Ph.D. Electrical Engineering IIT Bombay

Introduction

Dialysis is one of the oldest biomedical system developed to replace some function of a particular diseased human organ. Kidney failure is one of the common diseases that effect a huge amount of population world wide. The most common and effective treatment is kidney replacement from another donor and a partially effective treatment is dialysis machines. But above all efforts End-Stage Renal Disease (ESRD) has high morbidity rate till now. The reasons behind this is shortage of donors, inefficiency of dialysis systems, and above all cost of treatment. In response to this extreme shortage, the criteria for accepting organs have been modified to include marginal donors such as non-heart beating donors (NHBD). Also, these treatments only provide intermittent filtration and re-absorptive function, and patients are at higher risk for further complications. Moreover, life expectancy drops to less than 20% for patients on renal dialysis treatments for periods of five years or more [1]. The dialysis systems present till now needs severe reformations and redesigning in terms of improved efficiency, smaller size to become portable (wearable or implantable), and affordability in terms of the cost. With the advancements in the field of MEMS micro-fabrication tools and material the sight of a wearable or implantable artificial kidney becoming clear. Several studies have shown improved clinical outcomes when haemodialysis is delivered for several hours every day (quotidian dialysis) compared to the conventional, thrice-weekly therapy [2].

Brief Working Principle of a Renal System

As we are talking about artificial kidney we should have some brief insight about the renal system, more specifically about the principle behind the working of a kidney. The kidney is essentially a microfluidic device that processes and removes wastes while maintaining the proper balance of electrolytes including sodium, potassium, calcium and magnesium, as well as the retention of sugars and blood proteins such as albumin. The waste along with water excreted from body as urine while the fresh waste free blood goes to the venous for

recirculation in the body.

Fig1: Basic block diagram of a kidney Fig2: Working principle of a kidney

The filtration operation is performed by a highly efficient semipermeable membrane which selectively passes molecules from blood. Another important task is to reabsorption of water, protein and other essential into blood. The membrane is consist of 1.2 million nephrons per kidney. A list of some of the typical materials to be excreted Material Urea Creatinine Different salts Uric acid Water Amount 30 g/day 2 g/day 15 g/day 0.7 g/day 1500 ml/day

Some typical reasons for kidney failure is accumulation of waste, acidosis, edema, hypertension, coma etc.

Thus a typical conventional dialysis system should have similar arrangements i.e. a filtration unit connected to the blood flow system.

Fig3.External dialysis machine [3]

Artificial Kidney
The device has two major blocks. Membrane: As mentioned in the previous section that the main functional block of a kidney consists of an efficient network of filtering membrane. Therefore, haemodialysis too requires high rates of blood filtration and well-controlled processing of the blood in order to precisely regulate critical levels of electrolytes, sugars and other blood constituents. Therefore, to produce an artificial kidney one need to realize this semipermeable network of membranes. This membranes is served as the engine of the dialysis system which retains the large and essential molecules in the blood and filters out smaller molecule such as urea, creatinine etc. and channelling them to the excretion route. As the drive to make dialysis systems portable (wearable or implantable) there is a requirement of significant improvements in membrane

properties to achieve the ultra-filtrate flux, solute transport rates, and immune-isolation. Thus the membrane is made of biocompatible material with micro-fabricated well-shaped pores.

Fig4.Membrane cross-section [2]

Conventional polymer filtration membranes usually have poly-disperse and irregular shaped pores, making it difficult to achieve the desired hydraulic permeability while maintaining an absolute barrier to macromolecular passage. Track-etched membranes can largely eliminate poly-dispersity in pore size, but the membranes tend to be fairly thick (approximately 10 m) and they must have low porosity (<2%) to minimize the formation of overlap ping pores (ion tracks) that would compromise immune-isolation. The control of pore geometry can potentially provide novel opportunities to optimize molecular transport rates. A membrane with uniform pores can reduce resistance to fluid flow while maintaining molecular selectivity compared to poly-disperse porous materials. Controlled pore shape, such as elongated or slit-shaped pores, also provide additional reductions in hydraulic resistance when compared with round or irregular pores. Thus, MEMS-based membranes are fundamentally enabling for miniaturization of renal replacement devices to a wearable or implantable size, whether for conventional therapies or for an implantable artificial kidney.

Fig.5. The principle of Haemodialysis [5]

Some Fabrication Aspects:

Silicon Nano pore Membranes (SNM) can be fabricated from silicon substrates by an innovative process based on MEMS technology. The surface micromachining scheme can be employed by introducing a sacrificial layer of SiO2. The sacrificial layer then patterned for pores with precision and after entire fabrication this sacrificial layer is etched out. Thermal oxide growth can give precise thickness down to 5nm which implies lower membrane thickness. Extensive cleaning by Piranha and RCA of the wafers needs to be perform to ensure no organic and inorganic impurities remains in the membrane. Then thermal oxidation is done to grow SiO2 followed by low pressure chemical vapour deposition (LPCVD) growth of a poly-silicon as the membrane. After fabricating the different calibration and test to be performed to make device safe for medical use e.g.
a. Surface Modification

To limit membrane fouling by globular proteins, the surfaces of materials described above were covalently modified with polyethylene glycol (PEG), modified to omit all sonication steps and continuing the PEG deposition for 12 hours. It is well established that attachment of PEG can significantly reduce protein adsorption and improve biocompatibility of a variety of surfaces.
b. Protein Sieving and Hemofiltration

Hemofiltration refers to the removal of an ultra-filtrate of plasma in which there is no solute loss by diffusion, since the plasma flowing through the filter is not exposed to dialysate flowing on the other side of the membrane. Protein Sieving is the ability of a solute to convectively cross a membrane [4]. Membrane arrays has to undergo differential interference contrast light microscopy for defects. Membrane hydraulic permeability to be evaluated using phosphate buffered saline (PBS), with the flow rate evaluated by timed collection over a range of pressures from 3.4 to 13.8 kPa. The data were used to calculate the mean pore size, h, as 12 3 =( )
1

Where L (membrane thickness) and w (long dimension of the slit pore) were measured by scanning electron microscopy, is the viscosity of the PBS, and Q/P is the slope determined by linear regression of the observed flow rate versus pressure data [3].
c. Protein Adsorption

Protein adsorption is process of testing accumulation and adhesion of particular molecules to the membrane surface. [5]
d. Blood Coagulation

The bare Si surface and the modified PEG surface has to tested for blood coagulation as the previous steps goes through several anticoagulant material. The test ensures proper cleaning without any residue.

Degassing Unit: Another important block is the degassing unit that helps to clean blood in terms of filtering out its undesired dissolved gasses. Degassing can be done physically or chemically. Chemical degassing is though useful for lab purposes its impractical for medical use as it can introduce other complexities [6]. For physical degassing the best solution which is being used in dialysers, are diffusion using vacuum pumps, but miniaturisation of this pump is been a real challenge. Though lots of micro-pumps have come up but still now no diffusion pump has not be miniaturised. Another alternative which is used in labs extensively is boiling of water can be thought of but it is unrealizable in medical systems. Thus another schemes of inserting bubble into the blood using ultrasound cavitation method is used. Lead Zirconate Titate (PZT) ceramics are excited to generate and ultrasound. For ultrasound cavitation it is important to maintain a controlled profile of temperature and pressure. The dialysate must be heated up to body temperature and drawn to the degassing chamber using negative pressure. This temperature and pressure profile helps the gasses dissolved in dialysate to form bubble and comes out. The bubble formation reduces the effective exchange surface area. Therefore the concentration of the dissolved gasses should be kept low to ensure efficient osmotic exchange. Some Fabrication Aspects:

The degassing chamber is made of a number of micro-channel curved out of a silicon substrate. The channels are made for venting the bubbles. The inlet and outlet is fabricated by

micromachining a Pyrex glass. Each channel has a typical dimensions of 2.7m2m with a depth of 20m. the entire chamber is encapsulated using a silicon glass via anodic bonding. PZT ceramic is attached to chamber using epoxy resin.

Fig 6. Schematic of Degassing unit [6]

Fig 7. Cross-section of degassing unit along AA [6]

Final Device: Each unit cell of the final device for this haemodialysis approach is a bilayer device with lateral flows of blood and waste in a counter-current fashion, separated by a thin ultrafiltration membrane. As shown in fig each bilayer device contains a planar network of blood-carrying vessels and a compartment for waste (dialysate), sandwiched together with an intervening ultrafiltration membrane. To replace the current dialysis system the portable device should have large filtration capacity, thus approximately 100 layers need to meet the requirements.

Fig8. Bilayer configuration of ultrafiltration device [1]

References:
1. Kaazempur-Mofrad M. R., Vacanti J.P., Krebs N.J., Borenstein J.T. A MEMS-Based Renal Replacement System Solid-State Sensor, Actuator and Microsystems Workshop, South Carolina June 6-10, 2004. 2. William H. Fissell, Anna Dubnisheva, Abigail N. Eldridge, Aaron J. Fleischman, Andrew L. Zydney, and Shuvo Roy High-Performance Silicon Nanopore Hemofiltration Membranes J Memb Sci. 2009 January 5. 3. http://en.wikipedia.org/wiki/Hemodialysis, 1st Nov. 2012, 23.30. 4. http://www.uptodate.com/contents/drug-removal-during-continuous-renalreplacement-therapy, 2nd Nov. 2012, 14.10. 5. http://en.wikipedia.org/wiki/Protein_adsorption, 2nd Nov. 2012, 12.16. 6. Zhen Yang, Sohei Matsumoto, Ryutaro Maeda, A prototype of ultrasonic micro degassing device for portable dialysis system Sensors and Actuators A 95 (2002) 274280.