This is my Final Project for the HTGAA2022 course 🧬🧫🤖
Patients living with chronic diseases need a routine check-up in order to have control over their health. Today there are limited portable medical devices that allow patients with chronic diseases to routinely monitor their values. For patients with phenylketonuria, this is a milestone of real importance, as this is a treatable disease. Good control can allow patients to live a full life without major complications. However, patients with diseases that require the control of analytes that are difficult to diagnose, such as amino acids, are often limited to good control due to the lack of access to these tests. Either for economic reasons or for geographical reasons. Therefore, this project proposes the creation of medical devices for urinary analysis, for the routine control of two amino acids (phenylalanine and tyrosine). These devices will be based on the use of the TyrR protein that acts as a transcription factor. The armed circuit will also count as chromo-protein reporters, which avoids the need for more specialized equipment to read the result. Furthermore, this circuit will be positioned as a freeze-dried cell-free system, which will be coupled to paper-based microfluidic devices designed for this study. The use of this type of device is expected to help improve the quality of life of these patients with orphan diseases.
Medical devices involve on Point-care have been explore for management of different diseases and physiological states of human body. Nonetheless, their integration on global markets has not reached all possible consumers. For some devices prices tend to be hight, while others are nonexistent in terms to meet the needs of consumers. The creation of medical devices and their application on point care diagnosis for chronic diseases, has proven to be a positive intervention on patients health. Perhaps the best example would be the AccuCheck device, which brings the ease that diabetes patients have today to monitor their blood glucose . This device has allowed timely and routine controls to be carried out, making possible real time intervention on environmental factors or other variables like drug dose readjustment, which have allowed better control. Results has prove a better evolution of the patient illness.
SFig1. Accu-Chek device used for control in glycemia levels
An important issue when designing a home take test should be the accessibility to patients’ sample, for instance will patients feel confident enough to perform any interventions to their own body? Some will not feel confident enough to perform any kind of extraction no matter how slightly painful it is like a prick with a lancet. That is why we should focus on using different body fluids that present an easy and 100% secure intervention when sampling. Urine is one of the most representative fluids for analysis of diseases  (Rifai et al., 2014). This fluid is a time related representation of the physiologic state of a a living organism since urine is an ultrafiltered of blood.  Urine normally carries what is in excess in the body or need to be excrete. In an altered state of physiology, we can find some different molecules (analytes) that could help identify or control a particular disease (Liao & Churchill, 2001). The collection of the samples and their analysis is relatively simple, making this body fluid a perfect candidate for use in a sensing device.
SFig 2. Renal filtration process.
Patients’ whit phenylketonuria (PKU) an innate error of metabolism, present an altered physiological cycle of phenyl alanine (phe) and tyrosine (tyr) inside their bodies. Malignancy caused by a lost function mutation present inside the phenylalanine hydroxylase (PHA) gene. This enzyme normally converts phe into tyr by introducing a hydroxyl group inside the aromatic group of phe. Loss of function on this enzyme change the normal ratio of phe:tyr, leading to an abnormal rise of phe and a decrese of tyr in body fluids. Malignancy of this disease is caused by this abnormal ratio, that disturb cellular development, especially on nervous system tissues (De Lucca et al., 2017; Ministerio de Salud Pública, 2013; van Spronsen et al., 2021). Chronic states of the disease often guide to high levels of mental disability and are related to the appearance of other severe characteristics. Patients that are involve on routinary quantifications of their body fluids ratio present better outcomes. This, combined with the use of pharmacological, dietary, and other hi-tech interventions that enhance their metabolism (Cunningham, 1971; Goodwin et al., 2016; Kennedy, 1973; Matalon & Michals, 1991)
SFig 3. PKU infirmative sheet