Hardware: A Smart Thermo-Responsive Microneedle Patch

A Patient-Friendly Alternative

For patients hesitant about the biological route, the patch offers a painless, minimally invasive method to deliver therapeutic proteins directly through the skin, overcoming psychological barriers.

A Precision Tool for Synergistic Therapy

The patch can work in tandem with the engineered bacteria. While the bacteria maintain a baseline therapeutic level, the smart patch can deliver programmed, on-demand boosts of the drug at critical moments, ensuring the concentration remains within the optimal therapeutic window.

The Pain Points of Conventional Drug Delivery

Traditional drug delivery methods, such as oral administration or intravenous injections, face significant challenges. Oral drugs often suffer from low bioavailability due to the first-pass effect in the liver and degradation in the gastrointestinal tract. Injections, while more direct, are associated with pain, risk of cross-infection, and a high dependency on professional healthcare providers and cold-chain logistics. These issues are particularly acute for patients with chronic diseases and for children, severely impacting treatment efficacy and quality of life.

Microneedles: A Promising Alternative

To overcome these limitations, we focused on microneedle-based transdermal drug delivery technology. Microneedles can painlessly penetrate the skin's stratum corneum barrier, delivering therapeutics directly and efficiently into the dermal layer. For large-molecule biologics like proteins and peptides, this method can increase delivery efficiency by several orders of magnitude compared to conventional patches. This painless, minimally invasive, and self-administrable approach greatly enhances patient compliance and safety while reducing medical waste.

Our Goal: From Passive Release to Active Smart Control

However, we identified that most existing microneedle patches are passive systems, where the drug release rate is dictated solely by the material's dissolution properties. This lack of control makes it difficult to meet complex clinical needs. We recognized a critical unmet need for a system capable of active and precise control over drug release. By actively controlling the dissolution rate of the microneedles, we can achieve programmed, pulsatile, or on-demand delivery profiles, thus maximizing therapeutic efficacy.

Therefore, our hardware project—the "Smart Thermo-Responsive Microneedle Patch"—was born. Our goal is to develop a flexible bioelectronic device that integrates wireless control, a thermal-response module, and a microneedle array to transform the conventional passive delivery paradigm into a next-generation active, intelligent, and controllable system.

Hardware Engineering

The core of our hardware design is modularity and integration. We broke down the complex electronic system into several key modules: a Master Control Unit (MCU), a wireless communication module, a power management module, and a temperature control driver module. This approach allowed us to develop and test each component independently, significantly improving development efficiency and system reliability.

In our V1.0 prototype, we successfully integrated these modules onto a single Flexible Printed Circuit Board (FPCB) and designed an innovative multi-layer structure (FPCB - Flexible Thermal Insulation Substrate - Heater - Microneedles). This architecture not only fulfills functional requirements but also considers the biocompatibility, flexibility, and safety essential for a wearable device. Through precise circuit design, we achieved fine-grained control over the heating power, which forms the physical basis for precise drug release.

Software Engineering

The software acts as the "remote control" and "brain" of our system, with a focus on user-friendliness and robust communication. We developed a mobile application with an intuitive graphical user interface (GUI), allowing even non-professionals to easily program complex delivery schedules (e.g., rapid bolus, linear slow-release, pulsatile delivery).

The app communicates with the hardware via Bluetooth Low Energy (BLE), ensuring stable connectivity and low power consumption to extend the device's operational life. On the firmware side, we implemented efficient algorithms to parse commands from the app and translate them into precise PWM control signals. Crucially, we integrated a PID temperature closed-loop feedback control algorithm based on an NTC thermistor. This ensures the heating process is accurate and safe, preventing temperature overshoots that could cause skin damage. The seamless integration of hardware and software is what ultimately translates user intent into precise physical action.

Overall Architecture

To achieve our goal, we designed a multi-layered, highly integrated flexible bioelectronic patch. Our V1.0 prototype, shown below, consists of four core synergistic layers:

1. Flexible Printed Circuit Board (FPCB): The "brain" of the system, housing the microcontroller (MCU), Bluetooth module, power management unit, and driver circuits. Its flexibility ensures conformal contact with the skin for user comfort.
2. Flexible Substrate: Positioned between the FPCB and the heater, this layer provides critical thermal and electrical insulation, protecting the sensitive electronics from heat.
3. Heater: The "heart" of our active control system. It generates precise Joule heat based on commands from the FPCB to modulate the microneedle's microenvironment.
4. Microneedle Patch: The drug delivery effector, where therapeutics are encapsulated within a biodegradable polymer matrix that dissolves at an accelerated rate upon thermal stimulation.

Workflow & Electronics Design

Our system establishes a complete closed-loop control pathway, from user command to precise drug release:

The user sets the desired delivery profile via a mobile application. This command is transmitted via Bluetooth Low Energy (BLE) to the MCU on the patch. The MCU then generates a specific Pulse-Width Modulation (PWM) signal, which drives the heater via a MOSFET switch circuit. An integrated NTC thermistor provides real-time temperature feedback, ensuring the temperature is precisely maintained, which in turn allows for dynamic control over the drug release rate.

Core Components Table:

Module	Model / Solution
MCU	ATmega328P
Bluetooth Chip	ECB02C
Power Management IC	IP5306
Serial Driver IC	CH340C
Buck Converter	AMS1117
Temperature Control	MOSFET Switch Circuit + NTC Thermistor

V0 - The Initial Attempt

We began by trying to replicate a method for creating a MWCNT/PDMS nanocomposite film from existing literature [1]. However, due to equipment limitations, we had to modify the protocol (e.g., using natural sedimentation instead of vacuum filtration).

Result: The CNT film formation was extremely poor, leading to a failed attempt. This taught us that direct replication is not always feasible and we needed to develop our own method from the ground up.

V1 - A New Approach

We hypothesized that directly mixing CNTs into the PDMS matrix before curing might yield a better result.

Result: The film formation was excellent, creating a flexible material. However, it was almost an insulator. The conductivity was far too low for effective Joule heating.

V2 - Introducing a Conductive Network

To solve the conductivity issue, we embedded a copper mesh into the V1 CNT/PDMS composite.

Result: This version was conductive, but the heat distribution was highly uneven, concentrating around the mesh wires. This would lead to inconsistent drug release.

V3 - Exploring Alternative Fillers

We went back to the V1 formulation and tried adding copper powder instead of a mesh, hoping for a more uniform dispersion of conductive particles.

Result: The film quality was good, but like V1, it remained nearly non-conductive. The copper particles did not form an effective percolating network.

V4 - The Synergistic Solution

Learning from our past attempts, we combined the ideas from V2 and V3. We hypothesized that the copper powder, while not providing conductivity, could act as an excellent thermal conductor to distribute the heat generated by the copper mesh. We fabricated a film by embedding the copper mesh into a PDMS matrix filled with copper powder.

Result: Success! The copper mesh was fully embedded, and the heat distribution was significantly more uniform across the surface. This synergistic design became our final, optimized heater film.

Heater Performance Characterization

We characterized the performance of our final (V4) heater film. The results demonstrate its capability for stable and uniform heating.

Temperature Control Accuracy

We tested the system's ability to regulate the heater's temperature at different PWM duty cycles. Our data shows that the system can rapidly reach and maintain the target temperature within a ±0.5°C range, demonstrating the precision and stability of our temperature control loop.

Temperature-Controlled Drug Release

This experiment validates the core function of our hardware. We integrated our device with microneedle patches loaded with a model drug (Rhodamine B) and measured the release kinetics at different temperatures. The results clearly indicate a significant positive correlation between temperature and release rate, proving that our hardware can actively modulate drug delivery.