In recent years, hyperuricemia in China has shown a significant increase and a younger trend. The overall prevalence rate of hyperuricemia in China is 13.3% [1], and the number of patients is about 177 million [2]. Hyperuricemia has become the fourth "habit disease" after diabetes, hypertension and hyperlipidemia.

Hyperuricemia refers to the disorder of purine metabolism, excessive uric acid secretion or renal excretion dysfunction, which makes uric acid accumulate in the blood. [2]

Therefore, various factors affecting uric acid level include:

1. Uric acid excess synthetic type. It is mainly due to single gene mutations such as ribose phosphate pyrophosphate syntheses and guanine ribose phosphate transferase, high purine diet, alcohol and fructose intake, which directly or indirectly affect purine anabolism, resulting in excessive uric acid production.

2. Uric acid excretion obstruction type. The change of transporters involved in the excretion and reabsorption of uric acid causes the disorder of uric acid excretion in the blood.

Hyperuricemia is the basis of gout. [5] If the increase of uric acid is not controlled, hyperuricemia will progress to gout.

Gout is a very painful disease. "At night, it was like a flash of lightning that suddenly struck my foot and hurt like a knife." When we interview a gout patient, we will hear him describe his painful symptoms like this. In fact, in China, the overall incidence rate of gout has reached 1.1% [1], and there are about 14.66 million patients suffering from gout [2].

Gout is a crystal related arthropathy caused by the deposition of monosodium urate (MSU), which is directly related to the metabolic disorder of purine and/or hyperuricemia caused by decreased uric acid excretion, and belongs to the category of metabolic rheumatism.

People with hyperuricemia have no obvious symptoms at the early stage, but when they feel joint pain and seek medical advice, they often have progressed to gout stage. At this time, gout stone has been deposited in the body and developed into arthritis, causing damage to bone and joints.

The common site of gout is the first metatarsophalangeal joint, but the joint of gout is not limited to this, but also includes other joints such as the foot back and knee joint. The joint of gout will eventually appear red, swollen, severe pain and other symptoms. [3]

Gout patients often have gout stones. It can be seen subcutaneously around the patient's ear, joints, tendons, soft tissues, etc. Gout stones formed in various parts of the body, especially in the limbs, not only seriously affect the shape of the limbs, but also lead to joint deformity, dysfunction, nerve compression, skin ulceration, and sinus failure, which requires surgical treatment. [4]

Gout can be complicated with kidney diseases, and in severe cases, joint destruction and renal function damage can occur, often accompanied by hyperlipidemia, hypertension, diabetes, arteriosclerosis and coronary heart disease. [3]

It is an indisputable fact that it is difficult to treat patients with hyperuricemia after they develop gout. At the same time, however, the development of high uric acid into gout takes a long time to accumulate. If we can use certain technologies to help patients detect uric acid and make them realize that they have hyperuricemia, we can effectively prevent this disease from developing into gout.

According to the Chinese Guidelines for the Diagnosis and Treatment of Hyperuricemia and Gout (2019), the diagnostic criteria for hyperuricemia are: the level of fasting blood uric acid twice on a different day exceeds 420 per liter for both men and women μ mol.[1]

According to the Guidelines for the Diagnosis and Treatment of Hyperuricemia and Gout in China (2019), it is recommended that all patients with hyperuricemia and gout should know and pay lifelong attention to the influencing factors of blood uric acid level, and always control the blood uric acid level within the ideal range. The increase of serum uric acid level is the fundamental reason for the occurrence and development of hyperuricemia and gout and their related complications. Long term compliance of blood uric acid can significantly reduce the frequency of gout, prevent the formation of gout stone, prevent bone damage, reduce the risk of death and improve the quality of life of patients, which is the key to prevent gout and its related complications. [1]

Among the many predisposing factors of hyperuricemia and gout, genetic factors, age composition, gender differences and other objective factors have different effects on gout. From the perspective of living and eating habits, the risk of hyperuricemia and gout is easily increased by liking high purine meat such as seafood and meat, drinking, smoking, obesity and irregular work and rest. [1]

Learn your uric acid level through daily monitoring, and improve your living and eating habits, which will help you have a "painless" healthy life.

At present, the most common method to detect uric acid level is through blood collection. According to the survey data in the 2021 White Paper on the Trend of Hyperuricemia and Gout in China, detection in hospitals is still the main way for online patients with hyperuricemia and gout to monitor uric acid. [7]

However, this method is not convenient for patients to realize daily monitoring. Nearly 20% of online patients began to choose household uric acid analyzer to find a more convenient detection way. [7]

We counted 27 brands of household uric acid detectors sold on China's largest online shopping platform, all of which tested the uric acid level by piercing the skin to take blood. We believe that this increases the pain of users and is not conducive to the popularization of daily monitoring of uric acid.

It is well known that the uric acid test in a regular hospital requires patients to arrive at the hospital in the morning and draw blood on an empty stomach. However, a large number of patients live near the hospital, so it is not easy for them to go to the hospital regularly. In addition, blood test, the detection mode of collecting samples, will also bring some pain to patients. Therefore, we consider that if we can design more convenient detection methods without trauma, we can improve the experience of patients and bring them a better quality of life.

This design should be able to prompt people whether their uric acid level exceeds the health standard, and prompt those who exceed the standard to go to the hospital for further careful examination and treatment.

So we thought that we could design a hand-held instrument to sense and prompt the level of uric acid by collecting urine. In this way, we can avoid the painful experience and fear brought by regular blood collection, and help people establish the habit of daily monitoring the uric acid level. 

We consider using the method of synthetic biology to design a uric acid sensor, which can conveniently monitor the uric acid level by collecting urine.

Initially, we assumed that the uric acid concentration detector has a sensing system, which works like this: we use the transcription factor HucR to sense the uric acid concentration. HucR from d.radiodurans strain belongs to MarR family. When the concentration of uric acid molecules in the urine is low, the transcription factor HucR binds to the promoter hucO, preventing RNA polymerase from binding to the promoter region, making gene transcription impossible. When the concentration of uric acid in urine is high, the binding of HucR and hucO is inhibited by uric acid molecules, so HucR cannot interact with hucO, RNA polymerase reaction proceeds normally, and gene transcription proceeds normally. 

Then, we designed a luminous system for this sensor. If the uric acid content in the urine sample exceeds the standard, after gene transcription of the previous system, there is a red fluorescent protein. After transcription and translation, the red fluorescent protein RFP converts the amplified uric acid concentration signal into a light signal, and judges the uric acid concentration by observing the luminous brightness.

However, in our experiment, we found that when gene transcription occurs in the sensing system, if there is less uric acid in the urine sample, the fluorescence signal output of the engineered bacteria will be weak. In order to ensure people's health and safety as much as possible, we hope that the detection limit of the sensing system is low enough, and the signal output level is as high as possible. Therefore, we designed an amplification system to amplify the uric acid concentration signal.

The amplifier system is mainly composed of two modular input and output terminals, which are constructed using hrp operons. The natural hrp contains two genes, HrpR and HrpS, which can be transcribed and translated into two proteins, R and S, which combine to form a high-order covalent complex HrpRS with high sensitivity. Through ATP hydrolysis, the hrpL promoter is activated, thus realizing the role of signal amplification. This part will be mentioned in the following pages.

So, finally, the uric acid detection device we designed includes three parts: sensing system, amplification system and luminous system. The first is a uric acid sensing system. When the uric acid content in urine is high, genes can be successfully transcribed and release signals. Then there is an amplification system, which is used to amplify the fluorescence signal of engineering bacteria. Finally, there is a luminous system, which will emit red light when the concentration of uric acid is high.

here are videos demonstrating how the system works