From finger prick sampling to wearable and implantable chem/bio-sensors

At a Glance

Metadata	Details
Publication Date	2017-02-09
Journal	Dublin City University Open Access Institutional Repository (Dublin City University)
Authors	Dermot Diamond
Analysis	Full AI Review Included

Technical Documentation & Analysis: Active Fluidics for Implantable Chem/Bio-Sensors

This analysis connects the requirements for advanced, long-term functional biosensor platforms—specifically those leveraging light-actuated microfluidic valves—to the superior material properties and customization capabilities of 6CCVD’s MPCVD diamond products.

Executive Summary

Problem Statement: Conventional biosensors (e.g., glucose monitoring) rely on disposable elements or short-term wearables (2 weeks), failing to meet the long-term goal of reliable, implantable platforms (target 10 years).
Core Innovation: The research demonstrates the use of Bioinspired Fluidics—soft polymer actuators (hydrogels) triggered by light (UV/Vis) to create fully integrated, reusable microvalves for Lab-On-A-Chip (LOAC) systems.
Material Science Focus: Poly(N-isopropylacrylamide) (PNIPAAM) hydrogels are utilized, exploiting the Lower Critical Solution Temperature (LCST, 30-35 °C) and volume change for actuation control. Spiropyran photo-switches enable precise, light-based control of the collapse/expansion cycle.
Achieved Performance: Demonstration of fast and reversible microfluidic flow control, achieving stable flow rates of ca. 4.0 µL/min, with robust durability confirmed over > 50 repeat actuations.
Relevance to 6CCVD: Realizing truly implantable, autonomous chemical sensors requires ultra-stable, fouling-resistant, wide-potential-window electrode materials, making Boron-Doped Diamond (BDD) the optimal choice for the integrated detector element within the active fluidic platform.
Future Direction: The pathway leads toward 3D ‘Soft’ Self-Aware Fluidics, demanding hybrid material integration, high-precision machining, and stable electrode surfaces.

Technical Specifications

The following parameters relate to the performance of the light-actuated microvalves for fluidic control, highlighting the operating requirements for integrated sensor components.

Parameter	Value	Unit	Context
Target Lifespan (Implantable)	10	Years	Required reliability for implanted devices (vs. 2 weeks for external patches).
Actuation Mechanism	Photo-switching	UV / Vis Light	Utilized to switch spiropyran between ‘Off’ (spiropyran) and ‘On’ (merocyanine) states.
Actuator Material	PNIPAAM Hydrogel	N/A	Polymer exhibiting inverse solubility; collapses above LCST.
Lower Critical Solution Temperature (LCST)	30-35	°C	Temperature range where PNIPAAM volume change occurs.
Controlled Flow Rate (Steady State)	ca. 4.0	µL/min	Achieved steady flow rate demonstrated by photovalve control.
Flow Rate Measurement Cycle (Fast)	60	Seconds (LED On)	Demonstrating quick response and flow generation.
Flow Rate Measurement Cycle (Pulsed)	1s On, 2s Off	N/A	Demonstrating highly controlled, oscillating flow.
Repeatability	> 50	Actuations	Verified reusability of the polymer valve structure.
Microstructure Fabrication Technique	2-PP (Two-Photon Polymerization)	N/A	Used to create micro-scale pillar arrays (Endo-Skeleton control).
Current Glucose Sensing Standard	2	Weeks	Lifespan of current external patch sensors (Abbott Libre).

Key Methodologies

The research utilizes a hybrid approach combining microfluidic chips (LOAC) with soft actuator materials to achieve active, controllable fluid transport.

Material Selection: Use of smart hydrogels, specifically PNIPAAM, which demonstrates a reversible volume change in response to thermal or chemical stimuli near its LCST (30-35 °C).
Photo-Switch Integration: Incorporation of spiropyran compounds into the polymer structure. Spiropyran provides optical control, converting UV or Vis light exposure into a structural change that locally alters the polymer environment or temperature, inducing the collapse/expansion necessary for valve actuation.
Microfabrication (LOAC): Utilizing techniques like 2-PP (Two-Photon Polymerization) to create highly resolved 3D microstructures, such as pillar arrays and flow channels, often embedded in materials like PMMA or PDMS.
Valve Operation: The valve functions by modulating the effective cross-sectional area of a microchannel. Light is pulsed onto the actuator, causing the polymer to collapse (expelling water) and block or restrict flow. Cessation of light (or change in wavelength/temperature) allows the polymer to rehydrate and open the channel.
Performance Verification: Measuring the cumulative volume and instantaneous flow rate (µL/min) through the microchannel over time under various pulsed light sequences (e.g., 60s continuous light vs. 180s pulsed light).

6CCVD Solutions & Capabilities

This research demonstrates a critical step toward integrated, long-term biosensing. 6CCVD’s ultra-pure diamond materials are essential for providing the robust, stable, and highly sensitive detector interface required to convert the chemical sample (processed by the active fluidics) into a reliable electronic signal, especially for applications targeting 10+ years of operation.

Applicable Materials

To replicate and advance the research presented, particularly in electrochemical sensing within the reaction manifold, 6CCVD recommends the following specialized CVD diamond materials:

Heavy Boron-Doped Polycrystalline Diamond (BDD):
- Requirement: Ideal for the integrated detector element within the LOAC. BDD offers the widest electrochemical potential window of any solid electrode, combined with exceptional chemical inertness and resistance to biofouling—critical features for long-term implantable devices processing complex biological fluids (blood, interstitial fluid, sweat).
- 6CCVD Capability: We provide high-conductivity BDD wafers/plates (PCD), enabling robust, stable sensing interfaces where polymer-based microfluidics can be bonded or integrated.
Optical Grade Single Crystal Diamond (SCD):
- Requirement: If the microfluidic system relies on internal or embedded light sources (UV/Vis LEDs) to control the photo-actuators, high-purity SCD can serve as a superior substrate or optical window due to its exceptional transparency and high thermal conductivity (critical for managing heat generated by embedded electronics/LEDs near the temperature-sensitive hydrogels).

Customization Potential

The integration of advanced soft fluidics necessitates precise alignment and complex geometry which standard substrates cannot support.

Research Requirement	6CCVD Customization Service	Value Proposition
Custom Footprint for LOAC	Custom Dimensions & Laser Cutting	Plates/wafers available up to 125mm (PCD), cut to specific microfluidic chip size requirements with high precision (e.g., circular electrodes, specialized channels).
Integrated Electrochemical Sensors	Custom Metalization Capabilities	We provide in-house deposition of critical contact metals (Ti, Pt, Au, W, Cu) required for bonding to polymer structures (PDMS, PMMA) or creating stable electrical interfaces for the BDD sensor element.
Substrate Thickness Control	SCD/PCD Thickness Precision	Offering thicknesses from 0.1 µm up to 500 µm (SCD/PCD wafers) or 10mm (Substrates), allowing engineers to precisely control thermal paths and mechanical stability required for hybrid device assembly.
Surface Preparation	Ultra-Smooth Polishing	Polishing standards achieved (Ra < 1nm for SCD, < 5nm for PCD) ensure stable, clean, and repeatable interfaces for the subsequent deposition of hydrogels and microfluidic layers.

Engineering Support

6CCVD recognizes that successful implementation of implantable sensing requires multidisciplinary expertise. Our in-house PhD team can assist researchers and engineers in selecting and specifying the correct diamond material—balancing electrochemical stability (BDD doping level) with optical transparency (SCD purity) and mechanical rigidity—for similar implantable chemical/biological sensor projects.

For custom specifications or material consultation, visit 6ccvd.com or contact our engineering team directly.

View Original Abstract

Despite the wide range of applications and tremendous potential of implantable sensors targeting chemo/bio-markers, bringing actual practical devices fully to market continues to be inhibited by significant technological barriers associated with long-term reliability, which is a key requirement for implantable devices. Wearable chem/bio-sensors offer an interesting approach, intermediate between the long-term vision of implantable devices, and the single use-disposable devices that are the current dominant use model. For example, wearable patch-type devices employing minimally invasive sampling of interstitial fluid for continuous glucose monitoring target a use period of about two weeks [1]. However, despite this apparently rather modest target, despite apparently promising breakthroughs, large-scale adoption is still frustratingly elusive, and products are still finding it difficult to establish markets. Moves by Google into the biosensing space are an interesting development, with the focus again being on how to gain access to sample fluids through which key biomarkers like glucose can be tracked in a non-invasive manner via a limited duration use model. Google, in partnership with Novartis, is focusing on glucose monitoring through a contact lens that can be powered inductively (no batteries), can communicate wirelessly, function for 24 hours (lenses are changed daily), has an integrated electrochemical sensor, and is in contact with a sample fluid (ocular humour) with glucose composition related (albeit somewhat fuzzily) to that of blood [2]. Similarly, the period up to the launch of the Apple iWatch witnessed a frenzy of speculation about whether it would have an integrated glucose monitoring capability [3]. In the end, the iWatch was launched, with no mention of any integrated chem/bio-sensing capability.\nHowever, once these initial applications are delivered, and the wearable platform possibilities more clearly resolved, the drive for more value will place the spotlight on other sensing technologies that can implemented on-body to provide new types of information. In this respect, chemical sensors and biosensors are obvious candidates, particularly for conditions like diabetes that demand long-term continuous monitoring. These devices are inherently more complex and less dependable than the well-established physical sensors, as reflected in the difficulties in bringing these sensors to market [4]. However, recent advances in real-time sweat electrolyte monitoring using wearable chemical sensing platforms are pointing the way forward [5,6]. In this paper, I will examine the issues that currently limit the applicability of chemo/bio-sensors in wearable and implantable scenarios, and present ways through which the effective autonomous lifetime of these more complex sensors might be extended from the current norm of (at most) several days, towards much longer periods (ideally years).\n\nReferences\n1. See for example http://diatribe.org/abbott-freestyle-libre-transforming-glucose-monitoring-through-utter-simplicity-fingersticks, last accessed 11th July 2016.\n2. See http://www.independent.co.uk/life-style/gadgets-and-tech/google-licenses-smart-contact-lens-technology-to-help-diabetics-and-glasses-wearers-9607368.html, last accessed 11th July 2016..\n 3. See for example http://www.phonearena.com/news/Apple-iWatch-to-arrive-in-October-with-curved-OLED-screen-blood-glucose-sensor-and-more_id56939, last accessed 11th July 2016.\n 4. Concept and development of an autonomous wearable micro-fluidic platform for real time pH sweat analysis, V. F. Curto, S. Coyle, R. Byrne, N. Angelov, D. Diamond and F. Benito-Lopez, Sensors and Actuators B-Chemical, 175 (2012) 263-270.\n5. T. Glennon, C. O’Quigley, M. McCaul, G. Matzeu, S. Beirne, G.G. Wallace, F. Stroiescu, N. O’Mahoney, P. White, D. Diamond, “SWEATCH”: A Wearable Platform for Harvesting and Analysing Sweat Sodium Content, Electroanalysis. 28 (2016) 1283-1289. doi:10.1002/elan.201600106. \n 6. W. Gao, S. Emaminejad, H.Y.Y. Nyein, S. Challa, K. Chen, A. Peck, H.M. Fahad, H. Ota, H. Shiraki, D. Kiriya, D.-H. Lien, G.A. Brooks, R.W. Davis, A. Javey, Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis, Nature. 529 (2016) 509-514. doi:10.1038/nature16521.

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Original Source

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