Team:Worldshaper-Shanghai/Description

Inspiration and Description

Inspiration

Our project was inspired by one gout patient around us who is also one of our instructors. When it comes to the pain and inconvenience caused by gout, we suddenly find that there are so many gout patients or people have hyperuricemia around us. Through further investigating, we draw the trouble out that the main troublesome the patient feel is the regular blood uric acid level detecting and the long waiting list for the results. So the idea of designing a portable and convenient uric acid monitoring device came into our mind.

Background

Definition & causes

Gout is a progressive, painful, debilitating form of inflammatory arthritis that has been affecting man since antiquity[1–3]. It is caused by factors that elevate the concentration of SUA (serum urid acid), leading to hyperuricemia[2,4]. Continued elevated SUA can result in MSU (monosodium urate) crystal deposition throughout the body, including joints, soft tissues, cartilage, and organs (e.g. kidneys)[5]. MSU crystals trigger the periodic occurrence of painful, acute, inflammatory flares[1,2]. If hyperuricemia persists, the acute gout flares may be superseded by long-term, chronic, tophaceous gout with bone and cartilage destruction[1,2]

Figure 1 Uric acid crystal in joint
Figure 1 Uric acid crystal in joint

The level of SUA is the net effect of dietary intake of purine sources, endogenous cell turnover, and UA excretion. Purines are converted to hypoxanthine, xanthine, and ultimately uric acid (UA) via the xanthine oxidase enzyme. Based on an average purine content diet, 800-1000mg of UA is produced daily. 500-600mg is produced endogenusly while the remaining 200-300mg is produced from dietary sources of purines. Approximately 70% is excreted by the kidney while the remainder is eliminated via the gastrointestinal tract, where it is degraded by bacterial uricase[6-11].

Figure 2 Purine Metabolism and Disposition of Uric Acid
Figure 2 Purine Metabolism and Disposition of Uric Acid

The imbalance between UA production and excretion is the hallmark of hyperuricemia and progenitor for monosodium urate crystal formation. Defective renal elimination of UA, known as UA underexcreters, accounts for 80%-90% of gout cases. Hyperuricemia and gout are also highly heritable with estimates of up to 45% and 65%, respectively. 24 inherited genetic disorders such as Lysch Nyhan Syndrome, which accounts for 10% of gout subtypes.[1,6,7,8]

Prevalence& Current situation

The prevalence and incidence of gout remain substantial for decades and show an increasing trend on a global scale. For example, the prevalence of gout in the US was 3.9% in 2007-2008. China had a pooled prevalence of 1.1% in 2010-2016. In the UK, the prevalence of gout was 2.49% , with a 63.9% increase during 1997-2012. In addition, the prevalence of gout in Italy increased from 6.7 per 1000 inhabitants in 2005 to 9.7 per 1000 inhabitants in 2009. The prevalence in Korea also increased from 3.49 per 1000 persons in 2007 to 7.58 per 1000 persons in 2015[12-16]. According to our public survey, among 2073 samples, 54% of the respondents have been exposed to or suffered from gout, which points out that gout has a high incidence in China. This indicates that there is a high demand for gout related products (Figure3). Additionally, we learned from Dr. Kong, the vice chief physician of the department of rheumatology and immunology in Changhai hospital, gout affects 100 million people in China, and 10 to 15 percent of people with hyperuricemia will turn to gout. Detecting urid acid becomes the most necessary and effective way for analyzing gout. Therefore, there is a large number of patients in the society and there is an impressing need for our project.

Figure 3 The gout coverage according to our public survey
Figure 3 The gout coverage according to our public survey

Current diagnosis measure

  1. Joint fluid test. A specialist uses a needle to draw fluid from your affected joint. Urate crystals may be visible when the fluid is examined under a microscope. Joint aspiration can be technically difficult and painful to the patient and is often deferred, to be conducted by a specialist (e.g., a rheumatologist or orthopedic surgeon)[17]. In addition, the accuracy of synovial fluid analysis may be affected by a number of factors (both patient-, practitioner-, and analyst-related)[18].
  2. Blood test. This is the most common way that doctor recommend to measure the levels of uric acid and creatinine in patients’ blood. It utilizes the chemical analysis of mildew in most hospitals. The result of high uric acid does not necessarily means the patient has gout, but it can be a primary warning index.
  3. X-ray imaging. Joint X-rays can be helpful to rule out other causes of joint inflammation. Accompanied with DR’s ubiquitous, the quality of scanned picture is improved. However, disadvantages still remain. During the early gout, using x ray can only present swelling of soft tissues. When x ray can truly reveal whether the patient has gout or not, it is usually late gout. Patients already lost the best opportunity for treatment[19].
  4. Ultrasound. Ultrasonography might show features of monosodium urate crystal deposition, such as the double contour sign, which is thought to represent monosodium urate crystals overlying articular cartilage. Also, the advantages are obvious: zero radiation, low expenses, multi-section inspection, high resolution and available for Dynamic assessment. Instead of X ray, ultrasonography is more sensitive but lack of specificity[20,21].
  5. Dual energy CT scan. Dual energy CT usually function distinguish between urinary calculi which gives priority to with uric acid or calcium salt. The results are really satisfying while the vivid color and 3D imaging are utilized in the picture. Definitely, CT has high rate of identifying gout nodules. This type of imaging can detect the presence of urate crystals in a joint even when it is not acutely inflamed. This test is not used routinely in clinical practice due to the expense and is not widely available[21].
  6. MRI. This method stands for nuclear magnetic resonance imaging, is dominant in tissue resolution and discover gout nodules, bone erosion. MRI is pretty helpful to doctors to evaluate the comorbid disorders. ƒHowever, high price is required and MRI itself has low specificity in identifying gout arthritis[22].

Our project goals

We made several professional interviews to decide our make our project direction. Dr. Zhang, the doctor in diagnosis department of 463 Hospital. She said that measurement of the concentration of SUA is the only method to diagnose gout in clinic so our project is meaningful. Dr. Kong, the vice chief physician of the department of rheumatology and immunology in Changhai, hospital told us that it is easy for hyperuricemia to develop into gout, so it is important for hyperuricemia patients to test their blood uric acid level. We know that patients spend much time, average 3 hours apiece, in blood uric acid level test in hospital in the interview with Ms. Huang who is from the marketing department of Abbott. In addition, our Human Practice also shows that 79% of the surveyed samples think it is troublesome about regular blood test in hospitals. In Human Practice, we learn that people score average 7.51 (the total score is 10) in their expectation for the portable test device, leading to the conclusion that our project is useful and promising. As a result, we plan to develop a portable test device.

Figure 4 public attitudes towards visit doctors and portable devices
Figure 4 public attitudes towards visit doctors and portable devices

In hospital one of the means that is used in practical indicating the chemical measure. This kind of way using chemical analysis is the best we can do. The main difficulty it faces is its time consuming and inconvenient. If someone involves in a formal urid acid diagnosis process, which means from lining up to get oneself report. The time differs from hospitals to hospitals depending on what quality your hospital is. In general, the time consumes from 1-3 hours. Therefore, for most of the time what patients and doctors can do is staring at each other and wait. Because this kind of diagnosis nowadays can only be taken in hospital, travelling can add inconvenience as well.

This year, we luckily found the uric-acid related Hypothetical uricase regulator (HucR) and pHucO promoter from Deinococcus radiodurans, association of HucR to uric acid leading HucR leave pHucO[23]. Our goal is to inspect the blood uric acid in patients with gout by using HucR and pHucO. In organisms, HucR inhibits the translation of downstream gene due to the combination with pHucO which controls the translation process of downstream gene. When there is some uric acid, HucR immediately combines with urid acid, make a conformational change and loses function. Then, the downstream gene can be translated. In our project, we take advantage of this phenomenon of binding and dissociation and put it into our portable detective devices. In order to establish the mathematical relationship between uric acid and HucR, our team decided to use the red fluorescent protein---mcherry as the reporter, we made it as a fusion protein with HucR and established a linear relationship between fluorescence and uric acid successfully by using cellulose acetate membrane method. We also did our efforts to finished the future applicated design, called “easy (blood) uric-acid monitering kit” that can be taken home by gout patients, and its volume will not be larger than a medium-sized handbag. Patients only need to take a small amount of blood and seperate serum by using a simple tools, then put the sample into portable device and got results. we hoping it can provide gout patients with a efficient&fast way to monitor uric acid in the future.

References
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