Hemodialysis Inline Analysis - Senior Design Day

Background
Finding a Resolution
Our Focus
Design Needs, Wants and Specifications
Prototype Designs
Testing Results and Suggested Improvements
Future Works to Optimize Current Prototype
Meet the Team

Background

In 2019, over 700,000 Americans were diagnosed with End-Stage Renal Disease (ESRD), according to the US Renal Data System [1]. ESRD is the most advanced stage of chronic kidney disease (CKD) characterized by complete, irreversible kidney failure, unable to maintain life [2]. ESRD patients must undergo regular dialysis treatments or receive a kidney transplant.

Hemodialysis – the most common form of dialysis in the United States – filters the blood to remove toxins and built-up fluid with a dialyzer filter. Essentially, hemodialysis acts like an artificial, external kidney. Most treatment plans require patients to travel to the clinic 3 – 4 times every week for four hour appointments where they must sit hooked-up to the dialysis machine. This time consuming process reduces the quality of life for patients and limits their independence. Additionally, during the interdialytic period (time between treatments), patients experience a significant buildup of toxins and fluid in their blood, which can result in cardiac complications, such as heart attack or stroke, that can be fatal. Unfortunately, most people on dialysis have only a 40-50% chance of survival for the first five years of treatment [3, 4].

Figure 1: This is a simplified image representing the function of dialysate where the filter in the machine helps remove the uremic toxins from the blood into the dialysate.

Recently, there has been a gradual increase in the number of patients that opt into at-home hemodialysis treatments. At-home treatments provide a more flexible schedule and improved patient outcomes. Current at-home machines have very limited portability and still require patients to remain stationary for multiple hours. Designing a portable hemodialysis system would allow patients a greater sense of independence and could dramatically improve health outcomes and quality of life by eliminating the interdialytic period.

Finding a Resolution

Our customer is working towards developing a portable hemodialysis device, roughly the size of a backpack. The design is intended to filter the dialysate solution through the system as it is used so that it can be recirculated. Creating a component to monitor the concentration of uremic toxins in the dialysate in real time will be critical to ensure that the recirculating dialysate is adequately purified with each pass through the filter. This would be a method to validate the functionality of the filter.

Our Focus

The objective of this project is to develop a benchtop model of an inline analyzer that can measure the concentration of urea in spent dialysate with potential to be introduced into a portable hemodialysis machine in the future.

Figure 2: Overall System Design where the LAHMB device is our customer’s current benchtop model for working on developing a portable hemodialysis machine and the green box is our device. The flow chart to right indicates the general pathway of our DIY Near IR- Spectrophotometer in relation to the rest of the system’s components.

Design Needs, Wants and Specifications

Rank	Needs	Metric	Goal
1	Detects urea in dialysate	Concentration	Urea concentration ≥ 1 mmol / L
2	Detects change in concentration	Percentage (%)	≤ 10%
3	In-line	# of samples removed from system	0
4	Speed of results	# of minutes	obtain measurement every 2 minutes
Rank	Wants	Metric	Goal
1	Portable size	Inches	10 – 20 in for benchtop model
2	Lightweight	Pounds	≤ 2 lbs

Table 1: Our prototyping process depends upon these established needs and wants where both the metric and goals were identified.

Prototype Designs

Desired Layout of Prototype Components for Stagnant Samples

The following images are for the layout of the prototype that should be used for future studies, for it incorporates all the necessary components: light source box, slit, diffraction grating, sample, photodetector circuit and Arduino board. The limitation of this design is that the halogen lamp (the light source) was too weak to create a proper light path through the slit and diffraction grating to hit the sample (cuvette). Thus, we could not continue testing the functionality of this layout.

Figure 3: Bird’s eye view of the set-up inside the box

Figure 4: Another bird’s eye view of the set-up

Figure 5: Close up image of the alignment of the diffraction grating and stagnant sample

Figure 6: Close up of the light source, slit, sample and photodetector circuit

Figure 7: This image replaces the breadboard with a PCB board, but testing this PCB circuit indicated inaccurate values. Hence, all measurements were taking with the breadboard circuit. Future goal would be to utilize a PCB board for a compact design.

Used Layout of Prototype Components for Stagnant Samples

The following two images demonstrate how data was collected for stagnant samples of different urea concentration values. The path includes the light source, slit, sample and photodetector circuit. This layout was chosen after the one suggested above did not seem to work as intended. Results from the data collected here will be shown later below.

Desired Layout of Prototype Components for Flow Samples

The images below indicate the system design for flowing samples. There were some adjustments in the placement of certain components due to a miscalculated error in the tubing alignment. Due to the time constraint, we could not make adjustments to match out initial design (similar to that for the stagnant sample), but we ensured that this design would still have the photodiode line up with the quartz cuvette in the tubing system.

Figure 10: Bird’s Eye View of the Prototype for Flowing Samples

Figure 11: Close-up Image of the Tubing system where the photodiode is aligned with the quartze cuvette

Figure 12: View of Device Integrated with Arduino Code and a Power Source for both the tubing system motor and halogen lamp light source

Figure 13: View of Design Integration and how measurements should be taken to eliminate any other light into the box

Testing Results and Suggested Improvements

Figure 14: Intensity values calculated for different urea concentrations with reference to our control (DI water) from the outputs of our photodetector circuit collected through the Arduino program.

The intensity values for different urea concentrations (2.5 mM, 5 mM, 10 mM, 20 mM, 40 mM) and our control (DI water) were calculated based on the output of our Arduino program. Based on this plot, it is clear that our system can detect a difference between a clear sample and a sample containing urea with implication that it can detect clear high/low values of urea concentrations. Further optimization of our prototype must be performed as there is no strong conclusive trend found from this analysis.

Future Works to Optimize Prototype

The primary goal for future work is switching to a more optimal light range. Based on literature, urea has distinct absorbances in the near infrared range closer to 4000-5000 cm-1 (2000-2500 nm) [5]. This range was not used here due to the scarcity and high cost of light sources and photodiodes in this range, which would have been impractical for early prototyping. In addition, one of the drawbacks of this prototype was the light source because it did not produce the necessary light path for a working do-it-yourself near-IR spectrophotometer.

Given that the cost of an LED in the 2050 nm – 2350 nm range is upwards of $100 [6]. Looking into other light sources, it would be suggested to evaluate the use of a 5W Tungsten Lamp Source ($835). Although this is a rather costly alternative, the specifications of this lamp suggest that it may be the best option. For example, it uses a constant current setting for stable performance, which would be beneficial for meeting the fourth need listed in Table 1- collecting samples every two minutes. In addition, this source would last for 10,000 hours increasing the longevity of the device [7]. Here it is important for the customer to re-evaluate his device’s life cycle and decide if he would prefer to replace certain components of the analyzer, or the entirety of the device. Lastly, the dimensions listed for this particular light source (101 mm x 64 mm x 41 mm) indicates that this may even be applicable when shifting from the benchtop model into a smaller size (for portability). Moreover, our financial constraints made it challenging to test the applicability of these light sources, so we would recommend our customer to look into this alternative as he continues to investigate incorporating a real-time analyzer that detects urea concentration in his LAHMB model.

Another aspect to consider is running multiple trials for the stagnant flows. Due to the limited access to the lab, we were unable to find conclusive results to identify if a trend has been seen. With a higher sample size, it will also make it more efficient to troubleshoot the design if needed. Additionally, it would be better if we use a conventional spectrophotometer to read the absorbance values for each of the samples tested. Then, compare these values to those found from the photodetector circuit. This would be a method to validate whether the prototype produces reliable and accurate results.

Meet the Team

Supervisors

Whasil Lee, Phd – University of Rochester Department of Biomedical Engineering

Julia Schroth – CMTI Biomedical Engineering Graduate Student

Customer

Dean Johnson, PhD – University of Rochester Department of Biomedical Engineering

Citations

[1] United States Renal Data System. “2019 USRDS Annual Data Report: Epidemiology of kidney disease in the United States.” National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2019.

[2] Abbasi, M. A., et al. “End-stage renal disease.” BMJ clinical evidence (2010). Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217820/.

[3] Romagnani, P et al. “Chronic Kidney Disease.” Nature Reviews Disease Primers, vol. 3,no. 1, Nov. 2017. [Online]. Available: doi:10.1038/nrdp.2017.88.

[4] Foley, R. N., et al. “Long Interdialytic Interval and Mortality among Patients Receiving Hemodialysis.” New England Journal of Medicine, vol. 365, no. 12, pp.1099–1107, Sep. 2011 [Online]. Available: doi:10.1056/nejmoa1103313.

[5] Olesberg, J. T., et al. “Online Measurement of Urea Concentration in Spent Dialysate during Hemodialysis.” Clinical Chemistry, Volume 50, Issue 1, 1 January 2004, Pages 175–181, https://doi.org/10.1373/clinchem.2003.025569

[6] Unmounted LEDs. [Online]. Available: https://www.thorlabs.com/newgrouppage9.cfm?objectgroup_ID=2814.

[7] “5W Tungsten Lamp Source (VIS-NIR Range): Edmund Optics,” Edmund Optics Worldwide. [Online]. Available: https://www.edmundoptics.com/p/5w-tungsten-lamp-source-vis-nir-range/13003/.

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