Ali K. Yetisen

Paper-based microfluidic point-of-care diagnostic devices

Dipstick and lateral-flow formats have dominated rapid diagnostics over the last three decades. These formats gained popularity in the consumer markets due to their compactness, portability and facile interpretation without external instrumentation. However, lack of quantitation in measurements has challenged the demand of existing assay formats in consumer markets. Recently, paper-based microfluidics has emerged as a multiplexable point-of-care platform which might transcend the capabilities of existing assays in resource-limited settings. However, paper-based microfluidics can enable fluid handling and quantitative analysis for potential applications in healthcare, veterinary medicine, environmental monitoring and food safety. Currently, in its early development stages, paper-based microfluidics is considered a low-cost, lightweight, and disposable technology. The aim of this review is to discuss: (1) fabrication of paper-based microfluidic devices, (2) functionalisation of microfluidic components to increase the capabilities and the performance, (3) introduction of existing detection techniques to the paper platform and (4) exploration of extracting quantitative readouts via handheld devices and camera phones. Additionally, this review includes challenges to scaling up, commercialisation and regulatory issues. The factors which limit paper-based microfluidic devices to become real world products and future directions are also identified.

Commercialization of microfluidic devices

Microfluidic devices offer automation and high-throughput screening, and operate at low volumes of consumables. Although microfluidics has the potential to reduce turnaround times and costs for analytical devices, particularly in medical, veterinary, and environmental sciences, this enabling technology has had limited diffusion into consumer products. This article analyzes the microfluidics market, identifies issues, and highlights successful commercialization strategies. Addressing niche markets and establishing compatibility with existing workflows will accelerate market penetration.

Nanotechnology in Textiles

Increasing customer demand for durable and functional apparel manufactured in a sustainable manner has created an opportunity for nanomaterials to be integrated into textile substrates. Nanomoieties can induce stain repellence, wrinkle-freeness, static elimination, and electrical conductivity to fibers without compromising their comfort and flexibility. Nanomaterials also offer a wider application potential to create connected garments that can sense and respond to external stimuli via electrical, color, or physiological signals. This review discusses electronic and photonic nanotechnologies that are integrated with textiles and shows their applications in displays, sensing, and drug release within the context of performance, durability, and connectivity. Risk factors including nanotoxicity, nanomaterial release during washing, and environmental impact of nanotextiles based on life cycle assessments have been evaluated. This review also provides an analysis of nanotechnology consolidation in the textiles market to evaluate global trends and patent coverage, supplemented by case studies of commercial products. Perceived limitations of nanotechnology in the textile industry and future directions are identified.

Contact lens sensors in ocular diagnostics.

Contact lenses as a minimally invasive platform for diagnostics and drug delivery have emerged in recent years. Contact lens sensors have been developed for analyzing the glucose composition of tears as a surrogate for blood glucose monitoring and for the diagnosis of glaucoma by measuring intraocular pressure. However, the eye offers a wider diagnostic potential as a sensing site and therefore contact lens sensors have the potential to improve the diagnosis and treatment of many diseases and conditions. With advances in polymer synthesis, electronics and micro/nanofabrication, contact lens sensors can be produced to quantify the concentrations of many biomolecules in ocular fluids. Non- or minimally invasive contact lens sensors can be used directly in a clinical or point-of-care setting to monitor a disease state continuously. This article reviews the state-of-the-art in contact lens sensor fabrication, their detection, wireless powering, and readout mechanisms, and integration with mobile devices and smartphones. High-volume manufacturing considerations of contact lenses are also covered and a case study of an intraocular pressure contact lens sensor is provided as an example of a successful product. This Review further analyzes the contact lens market and the FDA regulatory requirements for commercialization of contact lens sensors.

Holographic Sensors: Three-Dimensional Analyte-Sensitive Nanostructures and Their Applications

Nanostructures and Their Applications Ali K. Yetisen,*,† Izabela Naydenova,‡ Fernando da Cruz Vasconcellos,† Jeffrey Blyth,† and Christopher R. Lowe† †Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QT, United Kingdom ‡Centre for Industrial and Engineering Optics, School of Physics, College of Sciences and Health, Dublin Institute of Technology, Dublin 8, Ireland

Reusable, robust, and accurate laser-generated photonic nanosensor.

Developing noninvasive and accurate diagnostics that are easily manufactured, robust, and reusable will provide monitoring of high-risk individuals in any clinical or point-of-care environment. We have developed a clinically relevant optical glucose nanosensor that can be reused at least 400 times without a compromise in accuracy. The use of a single 6 ns laser (λ = 532 nm, 200 mJ) pulse rapidly produced off-axis Bragg diffraction gratings consisting of ordered silver nanoparticles embedded within a phenylboronic acid-functionalized hydrogel. This sensor exhibited reversible large wavelength shifts and diffracted the spectrum of narrow-band light over the wavelength range λpeak ≈ 510-1100 nm. The experimental sensitivity of the sensor permits diagnosis of glucosuria in the urine samples of diabetic patients with an improved performance compared to commercial high-throughput urinalysis devices. The sensor response was achieved within 5 min, reset to baseline in ∼10 s. It is anticipated that this sensing platform will have implications for the development of reusable, equipment-free colorimetric point-of-care diagnostic devices for diabetes screening.

Mobile Medical Applications

The development of medical smartphone applications (apps) can allow quantification of rapid diagnostics at point-of-care and enable clinical data collection in real time. Mobile medical apps can reduce the erroneous subjective readouts, and create a standard readout platform with connectivity options at low cost. This chapter demonstrates the development of an app algorithm that utilises the camera of the Android and iPhone smartphones to read colorimetric tests. This smartphone app can be used with dipsticks, lateral-flow and flow-through assays as well as aqueous colorimetric tests that are typically read by spectrophotometers or microplate readers. The mobile app was designed to provide on-site quantitative screening when rapid diagnosis is needed. The utility of the smartphone app was demonstrated through quantifying pH, the concentrations of protein and glucose in commercial urine test strips, which had linear responses in the ranges of 5.0–9.0, 15–100 and 50–300 mg/dL, respectively. The app can be adapted for semi-quantitative analysis of commercial colorimetric tests, rendering it an inexpensive and accessible alternative to more costly commercial readers.

Highly Stretchable, Strain Sensing Hydrogel Optical Fibers

A core-clad fiber made of elastic, tough hydrogels is highly stretchable while guiding light. Fluorescent dyes are easily doped into the hydrogel fiber by diffusion. When stretched, the transmission spectrum of the fiber is altered, enabling the strain to be measured and also its location.

A microsystem-based assay for studying pollen tube guidance in plant reproduction

We present a novel microsystem-based assay to assess and quantify pollen tube behavior in response to pistil tissues. During plant reproduction, signals from female tissues (pistils) guide the sperm-carrying pollen tube to the egg cell to achieve fertilization and initiate seed development. Existing pollen tube guidance bioassays are performed in an isotropically diffusive environment (for example, a semi in vivo assay in petri dishes) instead of anisotropically diffusive conditions required to characterize guidance signal gradients. Lack of a sensitive pollen tube guidance bioassay has therefore compounded the difficulties of identifying and characterizing the guidance signals that are likely produced in minute quantities by the ovules. We therefore developed a novel microsystem-based assay that mimics the in vivo micro-environment of ovule fertilization by pollen tubes in the model research plant Arabidopsis thaliana. In this microdevice, the pollen tube growth rate, length and ovule targeting frequencies were similar to those obtained using a semi in vivo plate assay. As a direct measure of the microdevices utility in monitoring pollen tube guidance, we demonstrated that in this device, pollen tubes preferentially enter chambers with unfertilized ovules, suggesting that the pollen tubes sense the concentration gradient and respond to the chemoattractants secreted by unfertilized ovules.

Photonic hydrogel sensors.

Analyte-sensitive hydrogels that incorporate optical structures have emerged as sensing platforms for point-of-care diagnostics. The optical properties of the hydrogel sensors can be rationally designed and fabricated through self-assembly, microfabrication or laser writing. The advantages of photonic hydrogel sensors over conventional assay formats include label-free, quantitative, reusable, and continuous measurement capability that can be integrated with equipment-free text or image display. This Review explains the operation principles of photonic hydrogel sensors, presents syntheses of stimuli-responsive polymers, and provides an overview of qualitative and quantitative readout technologies. Applications in clinical samples are discussed, and potential future directions are identified.