Inspiration
This is a real story!
Just when we were waiting for the second time brainstorm start in a day on March this year, we shared some news happened in our school. At that time, a team member told us that a schoolmate, who was in class2, grade10, had dropped out of school because of depressive disorder. That piece of news was astonishing, making us be upset immediately. Most of us know that student.
We knew she often felt depression, but we didn’t know she was too suffering from this disease to go to school. It was this event that made us to start searching for the resources of depressive disorder (we want to help her).
And at that brainstorm time, we found a video news reporting that about 24% children in primary and secondary school in China, according to the survey, have some extent of emotional or psychological problems, and some schools had set a rule that depressive disorder detection is requisite for students’ entrance. The problem is serious, so our project was decided to focus on the depressive disorder.
Fig.1 A video news reporting that about 24% children in primary and secondary school in China, according to the survey, have some extent of emotional or psychological problems.
Description
1. What is the situation of depressive disorder or MDD in the world?
Major depressive disorder (MDD), a serious problem for society, is a common emotional disorder and characterized by gloom, hypobulia, physical impairment, low mood, disproportionate situation, pessimism, world-weariness, and suicidal behavior [1].
According to a 2017 WHO survey, the number of people suffering from depression worldwide has reached 322 million, which means 4.3% of the world's population is affected [2]. MDD is a key factor for suicidal ideation and attempts, and the suicide rate in people suffering MDD is about 20 times that of the general population [3].
The average age of such mental illnesses has long been declining, as more and more teenagers are suffering from these diseases recently. Such serious mental illnesses require in-depth investigation and research to find more effective treatments.
Fig.2 The situation of MDD in the world.
2. What problems exist in diagnosis and therapy of depressive disorder or MDD?
The situation of depressive disorder is not optimistic. However, current diagnosis of this disease is mainly based on the patients' description of symptoms, assessment of mental status and evaluation of clinical behaviors, which are very subjective, increasing the rate of misdiagnosis that maybe develop to major depressive disorder (MDD), even leading to suicide.
It is reported that the misdiagnosis rate of MDD is more than 65%; the medical treatment rate of depressive disorder is very low; and 50% of patients are recurrent within 2 years after recovery. If the early depressive disorder patients could be diagnosed rapidly and intervened properly, or the MDD patients could be diagnosed correctly and objectively, they may receive appropriate medical treatments, preventing the occurrence of suicide.
So, it is urgent to find a sensitive and specific diagnostic method to increase the accuracy and objectivity of MDD diagnosis, helping clinicians make early screening and early intervention for MDD. This is a challenge to everyone. And we are ready to accept the challenge!
3. How to solve this problem?
To establish an objective diagnostic method for MDD, with the guidance of Dr. Liu, a professor in Shandong University, we read lot of literatures. And we found that miRNA, serving as a biomarker, could be used in the diagnosis of MDD [4,5]. Some miRNAs, such as miR-34a-5p, miR-221-3p and let-7d-3p, are upregulated in the serum, as well as in the Cerebral Spinal Fluid (CSF) of MDD[6].
So, we constructed the toehold switch reporter gene (for example LacZ gene) plasmids using pET-28a as a vector, which can express reporter proteins triggered by specific miRNA upregulated in MDD to detect the amount of miRNA [7]. At the presence of miRNA, the expression of report gene is switched on to express the reporter protein, which is easily measured, making the objective diagnosis of MDD is possible.
Fig.3 The mechanism of toehold switch plasmid.
4. How to achieve our goal?
To facilitate the reaction, storage and transportation, cell free system based on filter paper was used in our project. The cell free system with some other materials were lyophilized on the filter paper, on which a certain miRNA could be detected to make a biosensor[8]. It is conducive to long-distance transportation and storage, providing a portable biological reaction platform.
In order to develop a convenient and portable detector with the filter paper based biosensor to diagnose MDD, we have designed and printed a 3D device model to show how this detector works, which is shown in the follows:
Fig.4 3D printed device model, optical filter and filter paper biosensor.
To know the workflow of this detector, please refer to the hardware in the contribution section.
References
[1] Kennedy SH, Lam RW, McIntyre RS, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments. Can J Psychiatry. 2016;61(9):540-560. doi:10.1177/0706743716659417 [2] Bachmann S. Epidemiology of Suicide and the Psychiatric Perspective. Int J Environ Res Public Health. 2018;15(7):1425. doi:10.3390/ijerph15071425 [3] Fries GR, Zhang W, Benevenuto D, et al. MicroRNAs in Major Depressive Disorder. Adv Exp Med Biol. 2019;1118:175-190. doi:10.1007/978-3-030-05542-4_9 [4] Zhou X, Mao AQ, Wang XB, et al. Urine and serum microRNA-1 as novel biomarkers for myocardial injury in open-heart surgeries with cardiopulmonary Bypass. PLoS One. 2013; 8: e62245. doi: 10.1371/journal.pone.0062245 [5] Müller M, Kuiperij HB, Claassen JA, et al. MicroRNAs in Alzheimer's disease: differential expression in hippocampus and cell-free cerebrospinal fluid. Neurobiol Aging. 2014; 35:152-158. doi: 10.1016/j.neurobiolaging.2013.07.005 [6] Wan Y, Liu Y, Wang X, et al. Identification of differential microRNAs in cerebrospinal fluid and serum of patients with major depressive disorder. PLoS One. 2015;10(3):e0121975. doi:10.1371/journal.pone.0121975 [7] Green AA, Silver PA, Collins JJ, et al. Toehold switches: de-novo-designed regulators of gene expression. Cell. 2014;159(4):925-39. doi: 10.1016/j.cell.2014.10.002 [8] Yakoh A, Pimpitak U, Rengpipat S, et al. Paper-based electrochemical biosensor for diagnosing COVID-19: Detection of SARS-CoV-2 antibodies and antigen. Biosens Bioelectron. 2021; 176:112912. doi:10.1016/j.bios.2020.11291