Diabetes is a significant global health concern, and one of its life-threatening consequences is diabetic ketoacidosis (DKA), which is identified by increased acetone levels in perspiration. Current monitoring methods are invasive, requiring many blood draws that are uncomfortable and regular testing. It also requires regular user input, I plan to overcome these limitations through my project idea Broad Objectives: The broad objectives are to focus on fully non-invasive and passive detection and eventually try to integrate the detection system into a continuous monitoring mobile application interface Hypotheses: My hypothesis is that acetone, like other chemical inducers, can operate as a trigger by attaching to a designed riboswitch and activating gene expression. The specific goal is to create a riboswitch that activates in the presence of a volatile organic compound such as Acetone (like an ON switch), activating a reporter gene such as GFP when acetone is detected, giving fluorescence and giving indication of a metabolic condition like diabetes Specific Aims: My specific aims definitely correlation with my Aim 2 of the project i.e. making this system as full proof, sensitive and work on its shortcomings to increase its relevancy. Methods to be employed: I plan to design a Acetone detecting riboswitch using appropriate aptamer sequence, then analyze the behavior of the aptamer and acetone binding with computational softwares, verify if there is a conformational changes also analyze the binding affinity. This will include a circuit design, docking simulation, visualization of the binding, RNAFold analysis.
Diabetes is a chronic condition caused by either insufficient insulin production by the pancreas or ineffective insulin utilization by the body. Insulin is a hormone that regulates blood glucose levels. Hyperglycemia, commonly known as elevated blood glucose or blood sugar, is a common complication of untreated diabetes that causes catastrophic damage to many of the body's systems, particularly the neurons and blood vessels.
Humans are a continuous source of VOCs, emitted through both breath and skin. Studies like the ICHEAR project have shown that these emissions vary with temperature, humidity, and exposure to ozone. VOCs can persist indoors even after a person leaves, reacting with surfaces and air oxidants. Some of these byproducts are harmful, underscoring the need for reliable detection.
Many illnesses, including diabetes, obesity, hunger, and exercise, have been linked to hyperketonemia. An increase in blood,urine, breathe or sweat ketone body concentrations in diabetic patients indicates that the current treatment technique is unsuccessful, and diabetic ketoacidosis, a potentially fatal illness, may result.
Current (common) screening of diabetes relies on invasive, minimally invasive as well as non- invasive methods.
Gaikwad, A., Gauns, S., Borkar, M., Rodrigues, R., & Raykar, S. (2024). Comparative analysis of invasive and non-invasive methods for blood sugar measurement. International Journal of Creative Research Thoughts (IJCRT), 12(4). https://ijcrt.org/papers/IJCRT24A4706.pdf
All these screening methods are majorly based on glucose detection and come with their own limitations
| Invasive | Current Non-invasive methods |
|---|---|
| Painful, chances of infection | painless but can be inconsistent |
| Requirement of sample collection, mainly glucose | sweat,tear or saliva also interstitial fluid beneath the skin |
| Low to moderate sensitivity | Higher sensitivity |
| Integration into wearables is a challenge | complex optics can make the integration into wearables difficult |
| Also requires active user input like fasting, regular clinical checking or even pricking | can be expensive also low customizability |
Non-invasive diagnostics is a growing discipline that aims to eliminate patient discomfort and permit continuous monitoring. However, current non-invasive approaches, such as optical sensors, NIR spectroscopy, and glucose patches, have significant limitations, including low sensitivity to trace biomarkers, sensitivity to skin tone and hydration levels, motion aberrations, and expensive device prices. These disadvantages reduce its dependability and accessibility, particularly in low-resource or real-world environments.
My project idea presents a synthetic biology-based technique for detecting VOCs such as acetone from sweat via a genetically modified riboswitch circuit. This system combines biological amplification, modularity, and low-cost flexibility, making it a viable tool for accurate, real-time diabetes monitoring with sweat as a sample
Some of the challenges I faced would be mainly around the nature of acetone as a molecule, it being a small molecule, low sensitivity of VOCs in sweat, calibration and standardization as well as my third aim that is integrating this into a wearable.