6.3 Nanofluidic devices for drug discovery and delivery

Nanofluidic devices are revolutionizing drug discovery and delivery. These tiny systems, with channels smaller than 100 nanometers, allow precise control of fluids and molecules. They enable single-molecule detection, mimic body conditions, and speed up drug screening.

These devices are changing how we develop and deliver drugs. They help create targeted therapies, study drug interactions at the molecular level, and design smart delivery systems. This tech is paving the way for personalized medicine, making treatments more effective and tailored to each patient.

Nanofluidic devices for drug discovery and delivery

Principles and advantages of nanofluidic devices

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• Operate at nanoscale with channel dimensions below 100 nm allowing precise control and manipulation of fluids and molecules
• High surface-area-to-volume ratio enhances surface-dependent phenomena (adsorption and desorption) crucial for drug interactions and delivery mechanisms
• Enable single-molecule detection and analysis providing unprecedented sensitivity for drug screening and pharmacokinetic studies
• Precisely control fluid flow and molecular transport allowing more accurate drug dosing and targeted delivery to specific cells or tissues
• Mimic physiological conditions more accurately than traditional in vitro methods improving relevance of drug discovery experiments and reducing need for animal testing
• Miniaturization of drug discovery and delivery processes leads to reduced reagent consumption, faster analysis times, and higher throughput screening capabilities
• Integrate with other technologies (microfluidics and lab-on-a-chip systems) enabling comprehensive drug development platforms with enhanced functionality and efficiency

Applications in drug discovery and delivery

• Facilitate high-throughput screening of drug candidates against target proteins or cells
• Enable detailed studies of drug-target interactions at the molecular level
• Allow for precise control over drug release kinetics in controlled delivery systems
• Support development of targeted drug delivery strategies by manipulating nanoparticle-drug conjugates
• Provide platforms for studying drug metabolism and pharmacokinetics at the nanoscale
• Enable creation of artificial cell membranes for drug permeability studies
• Assist in formulation development by studying drug-excipient interactions in confined spaces

Fabrication techniques for nanofluidic devices

Lithography and etching techniques

• Photolithography and electron beam lithography pattern nanofluidic channels with e-beam lithography offering higher resolution for sub-10 nm features
• Reactive ion etching (RIE) and deep reactive ion etching (DRIE) transfer patterns from resist layers to substrate materials creating high-aspect-ratio nanofluidic structures
• Soft lithography techniques (replica molding and microcontact printing) utilized for rapid prototyping and mass production of nanofluidic devices using elastomeric materials (PDMS)
• Nanoimprint lithography (NIL) enables high-throughput fabrication with precise control over channel dimensions and surface properties
• Focused ion beam milling creates complex 3D nanofluidic structures for enhanced functionality
• Two-photon polymerization allows for direct writing of intricate 3D nanofluidic networks
• Interference lithography produces large-area periodic nanostructures for parallel nanofluidic channels

Materials and surface modification

• Common materials include silicon, glass, and polymers (PDMS, PMMA, COC) offering specific advantages in optical properties, chemical resistance, and biocompatibility
• Surface modification techniques (plasma treatment, chemical vapor deposition, self-assembled monolayers) tailor surface properties of nanofluidic channels for specific biological applications
• Atomic layer deposition enables precise control of surface chemistry and channel dimensions
• Nanoparticle-based coatings enhance surface functionality and introduce novel properties
• Biomolecule immobilization techniques (covalent attachment, affinity-based capture) create biorecognition surfaces
• Stimuli-responsive surface coatings (pH-sensitive, temperature-sensitive) incorporated for on-demand drug release or capture
• Nanostructured surface topographies (nanopillars, nanogrooves) engineered to enhance drug adsorption, cellular interactions, and controlled release kinetics

Challenges of nanofluidic devices

Fabrication and characterization challenges

• Maintaining precise nanoscale dimensions and avoiding channel collapse or deformation impacts device reproducibility and performance
• Integration of nanofluidic devices with macroscale systems for sample introduction and analysis presents challenges in interfacing and flow control across multiple length scales
• Limited throughput of some nanofluidic devices may hinder application in high-volume drug screening processes requiring parallelization or alternative strategies
• Characterization and validation of nanofluidic devices for drug discovery and delivery applications challenging due to small sample volumes and need for specialized analytical techniques
• Achieving uniform surface properties and channel dimensions across large-area nanofluidic devices
• Developing reliable and cost-effective mass production techniques for commercial applications
• Ensuring long-term stability and performance of nanofluidic devices under various environmental conditions

Operational and biological challenges

• Scaling effects lead to unexpected fluid behavior (increased viscosity and surface tension) affecting drug transport and interaction kinetics
• Surface fouling and biomolecule adsorption in nanofluidic channels alter device performance over time potentially affecting drug discovery assays and delivery efficiency
• Regulatory hurdles and standardization issues may slow adoption of nanofluidic devices in clinical drug discovery and delivery processes requiring extensive validation and quality control measures
• Maintaining cell viability and functionality in nanofluidic environments for long-term studies
• Addressing potential nanotoxicity concerns associated with nanofluidic materials and structures
• Overcoming limitations in sample preparation and handling for nanoscale volumes
• Developing robust and user-friendly interfaces for operation by non-specialists in clinical settings

Surface chemistry in nanofluidic devices

Electrokinetic phenomena and surface charge

• Surface charge density and distribution in nanofluidic channels significantly influence electrokinetic phenomena exploited for drug separation, concentration, and delivery
• Chemical modification of channel surfaces with functional groups (-COOH, -NH2, -OH) enables tuning of surface properties for specific drug interactions and controlled release mechanisms
• Zeta potential manipulation allows for control of electroosmotic flow and electrophoretic transport of charged drug molecules
• Double layer overlap in nanochannels leads to unique ion transport phenomena affecting drug behavior
• Surface charge patterning creates localized electric fields for drug trapping and concentration
• pH-responsive surface coatings enable dynamic control of surface charge for smart drug delivery
• Charge-based separation of drug molecules or nanocarriers in nanofluidic channels

Functionalization and biomolecule interactions

• Biomolecule immobilization techniques (covalent attachment, affinity-based capture) allow creation of biorecognition surfaces for drug screening and targeted delivery applications
• Stimuli-responsive surface coatings (pH-sensitive, temperature-sensitive) incorporated for on-demand drug release or capture in response to environmental cues
• Nanostructured surface topographies (nanopillars, nanogrooves) engineered to enhance drug adsorption, cellular interactions, and controlled release kinetics
• Surface functionalization with antifouling materials (PEG, zwitterionic polymers) helps maintain long-term device performance by reducing non-specific adsorption
• Integration of catalytic surfaces or enzyme-functionalized regions enables in situ drug activation or metabolism studies
• Molecularly imprinted polymers create specific binding sites for targeted drug capture and release
• DNA-based surface modifications enable sequence-specific drug interactions and programmable release mechanisms

Nanofluidic devices and personalized medicine

Personalized drug screening and analysis

• Enable rapid and sensitive analysis of individual patient samples facilitating personalized drug screening and selection based on genetic and molecular profiles
• Integration with wearable or implantable technologies allows continuous monitoring of drug levels and real-time adjustment of dosing regimens
• Manipulate and analyze single cells enabling study of drug responses at individual cell level potentially leading to more precise treatments for heterogeneous diseases (cancer)
• Facilitate development of organ-on-a-chip models accurately mimicking patient-specific physiology enabling personalized drug efficacy and toxicity testing
• Support high-throughput screening of patient-derived cells against drug libraries
• Enable real-time monitoring of drug-induced cellular responses at the molecular level
• Provide platforms for studying patient-specific drug metabolism and pharmacokinetics

Advanced drug delivery and monitoring systems

• Nanofluidic platforms used to develop and test novel drug delivery systems (nanocarriers and stimuli-responsive materials) for improved targeting and controlled release
• Miniaturization and automation capabilities lead to development of point-of-care diagnostic and drug monitoring systems improving accessibility to personalized medicine
• Enable creation of smart drug delivery implants combining sensing, decision-making, and controlled release functions for autonomous, patient-specific therapeutic interventions
• Support development of closed-loop drug delivery systems with integrated biosensors
• Facilitate creation of multifunctional nanoparticles for combined imaging and drug delivery
• Enable precise control over drug release kinetics based on individual patient needs
• Provide platforms for studying drug-drug interactions in patient-specific contexts