A Computationally Assisted Approach for Designing Wearable Biosensors toward Non‐Invasive Personalized Molecular Analysis

Abstract

Wearable sweat sensors have the potential to revolutionize precision medicine as they can non‐invasively collect molecular information closely associated with an individual's health status. However, the majority of clinically relevant biomarkers cannot be continuously detected in situ using existing wearable approaches. Molecularly imprinted polymers (MIPs) are a promising candidate to address this challenge but haven't yet gained widespread use due to their complex design and optimization process yielding variable selectivity. Here, QuantumDock is introduced, an automated computational framework for universal MIP development toward wearable applications. QuantumDock utilizes density functional theory to probe molecular interactions between monomers and the target/interferent molecules to optimize selectivity, a fundamentally limiting factor for MIP development toward wearable sensing. A molecular docking approach is employed to explore a wide range of known and unknown monomers, and to identify the optimal monomer/cross‐linker choice for subsequent MIP fabrication. Using an essential amino acid phenylalanine as the exemplar, experimental validation of QuantumDock is performed successfully using solution‐synthesized MIP nanoparticles coupled with ultraviolet–visible spectroscopy. Moreover, a QuantumDock‐optimized graphene‐based wearable device is designed that can perform autonomous sweat induction, sampling, and sensing. For the first time, wearable non‐invasive phenylalanine monitoring is demonstrated in human subjects toward personalized healthcare applications.

A Highly Selective Implantable Electrochemical Fiber Sensor for Real-Time Monitoring of Blood Homovanillic Acid

“…Distinguishing them from HVA is essential for the accurate monitoring of HVA in vivo . The MIP membrane of the HVA sensor is highly selective for target molecules in interferents because it contains binding sites that are complementary to the target molecules. − The binding sites were further characterized by DPV and electrochemical impedance spectroscopy (SI, Figure S11). The subsequent decreased peak current height in DPV and increased resistance in Nyquist plots indicated that the MIP without a target molecule extracted impeded the charge transfer at the electrode–solution interface due to the increased surface coverage by the polymer.…”

Recent Advances in Skin-Interfaced Wearable Sweat Sensors: Opportunities for Equitable Personalized Medicine and Global Health Diagnostics

“…34 Several recent examples demonstrate the use of iontophoresisbased sweat induction for extended and continuous sampling and analysis during physical exercise and at rest (Figure 4A). 56,158,159 of the sweat response for wearable sweat analysis platforms. 34 An alternative approach 160 for achieving long-term sweat collection utilizes a combination of hydrogels with paper microfluidic channels to facilitate passive (i.e., battery-free) osmotic sweat extraction at rest.…”

“…More conventional active sweat generation methods (e.g., exercise, temperature) present additional challenges for continuous measurements owing to inconsistent sweat rates . Several recent examples demonstrate the use of iontophoresis-based sweat induction for extended and continuous sampling and analysis during physical exercise and at rest (Figure A). ,, These efforts illustrate the potential of other cholinergic agonists to modify the duration and physical area of the sweat response for wearable sweat analysis platforms . An alternative approach for achieving long-term sweat collection utilizes a combination of hydrogels with paper microfluidic channels to facilitate passive (i.e., battery-free) osmotic sweat extraction at rest.…”

“…Recent Innovations: (A) Graphene-based wearable device, with material optimized by an automated computational framework, that can perform autonomous sweat induction, sampling, and sensing. Adapted with permission from ref Copyright 2023 Wiley. (B) Superhydrophobic sweat sensor to measure sweat vapor with flexible wireless communication and powering module for a standalone sensing system to continuously monitor insensible sweat rates.…”

Enhancing On-Skin Analysis: A Microfluidic Device and Smartphone Imaging Module for Real-Time Quantitative Detection of Multianalytes in Sweat

“…Wearable sweat sensors offer the remarkable capability to capture crucial physiological parameters in a noninvasive, on-site manner. − These sensors are emerging as promising alternatives to conventional methods, such as those relying on blood, urine, interstitial fluid, and saliva, for comprehensive physiological monitoring. , In the pursuit of in situ biomarker detection, sweat sampling has posed a challenge. However, innovative sampling approaches such as patches, electronic devices, and skin-interfaced soft microfluidic systems have emerged to address this concern. ,, Recent strides in microfluidic technology have ushered in a new era of noninvasive and economically viable diagnostic tools for monitoring sweat biomarkers. − An exemplar of this progress is the utilization of skin-interfaced soft microfluidic systems to discern biomarkers within sweat, offering invaluable insights into metabolic health. ,, An indispensable factor in the advancement of wearable sensors based on skin-interfaced soft microfluidics is the analytical signaling method. These methods play a pivotal role in the effective detection of sweat components, with colorimetric, electrochemical, and fluorometric assays being the forefront contenders. ,− Among these techniques, fluorescence assays stand out for their capability to detect species at remarkably low concentrations visually, providing a complementary approach. , However, conventional device designs necessitate chemical reactions to attain equilibrium, rendering materials like carbon dots, carbon polymer dots (CPDs), and natural chlorophylls .…”