Alexander Sun

A Multi-Technique Reconfigurable Electrochemical Biosensor: Enabling Personal Health Monitoring in Mobile Devices

This paper describes the design and characterization of a reconfigurable, multi-technique electrochemical biosensor designed for direct integration into smartphone and wearable technologies to enable remote and accurate personal health monitoring. By repurposing components from one mode to the next, the biosensors potentiostat is able reconfigure itself into three different measurements modes to perform amperometric, potentiometric, and impedance spectroscopic tests all with minimal redundant devices. A 3.9 × 1.65 cm2 PCB prototype of the module was developed with discrete components and tested using Googles Project Ara modular smartphone. The amperometric mode has a ±1 nA to ±200 μA measurement range. When used to detect pH, the potentiometric mode achieves a resolution of <; 0.08 pH units. In impedance measurement mode, the device can measure 50 Ω-10 MΩ and has been shown to have <; 6° of phase error. This prototype was used to perform several point-of-care health tracking assays suitable for use with mobile devices: 1) Blood glucose tests were conducted and shown to cover the diagnostic range for Diabetic patients (~200 mg/dL). 2) Lactoferrin, a biomarker for urinary tract infections, was detected with a limit of detection of approximately 1 ng/mL. 3) pH tests of sweat were conducted to track dehydration during exercise. 4) EIS was used to determine the concentration of NeutrAvidin via a label-free assay.

Yeast dual-affinity biobricks: Progress towards renewable whole-cell biosensors

Point-of-care (POC) diagnostic biosensors offer a promising solution to improve healthcare, not only in developed parts of the world, but also in resource limited areas that lack adequate medical infrastructure and trained technicians. However, in remote and resource limited settings, cost and storage of traditional POC immunoassays often limit actual deployment. Synthetically engineered biological components (BioBricks) provide an avenue to reduce costs and simplify assay procedures. In this article, the design and development of an ultra-low cost, whole-cell renewable capture reagent for use in POC diagnostic applications is described. Yeast cells were genetically modified to display both single chain variable fragment (scFv) antibodies and gold-binding peptide (GBP) on their surfaces for simple one step enrichment and surface functionalization. Electrochemical impedance spectroscopy (EIS) and fluorescent imaging were used to verify and characterize the binding of cells to gold electrodes. A complete electrochemical detection assay was then performed on screen-printed electrodes fixed with yeast displaying scFv directed to Salmonella outer membrane protein D (OmpD). Electrochemical assays were optimized and cross-validated with established fluorescence techniques. Nanomolar detection limits were observed for both formats.

Integration of Faradaic electrochemical impedance spectroscopy into a scalable surface plasmon biosensor for in tandem detection

We present an integrated label-free biosensor based on surface plasmon resonance (SPR) and Faradaic electrochemical impedance spectroscopy (f-EIS) sensing modalities, for the simultaneous detection of biological analytes. Analyte detection is based on the angular spectroscopy of surface plasmon resonance and the extraction of charge transfer resistance values from reduction-oxidation reactions at the gold surface, as responses to functionalized surface binding events. To collocate the measurement areas and fully integrate the modalities, holographically exposed thin-film gold SPR-transducer gratings are patterned into coplanar electrodes for tandem impedance sensing. Mutual non-interference between plasmonic and electrochemical measurement processes is shown, and using our scalable and compact detection system, we experimentally demonstrate biotinylated surface capture of neutravidin concentrations as low as 10 nM detection, with a 5.5 nM limit of detection.

Efficient power harvesting from the mobile phone audio jack for mHealth peripherals

A tremendous opportunity currently exists to enable practical and portable mHealth tools by taking advantage of the ubiquity of mobile phones across the world. To this end, we describe the design of a circuit to efficiently harvest energy from the standard audio jack of a mobile phone to power mHealth peripherals, lowering cost, reducing size, and improving the practicality of portable medical devices. This design not only obviates the need to charge or change an extra battery but also is universally compatible with all phones. The audio output channels of several popular phones were characterized in order to determine the range of design parameters. Using these data, different power harvesting topologies are presented, simulated, and compared. A PCB implementation was used to measure and confirm the performance. Compared with prior art, which have achieved 21% and 47% efficiency, this design is able to achieve greater than 77% efficiency by using a tunable impedance matching network.

An Audio Jack-Based Electrochemical Impedance Spectroscopy Sensor for Point-of-Care Diagnostics

Portable and easy-to-use point-of-care (POC) diagnostic devices hold high promise for dramatically improving public health and wellness. In this paper, we present a mobile health immunoassay platform based on audio jack-embedded devices, such as smartphones and laptops, that uses electrochemical impedance spectroscopy to detect binding of target biomolecules. This platform is intended to be used as a plug-and-play peripheral that reuses existing hardware in the mobile device, and does not require an external battery, thereby improving upon its convenience and portability. Experimental data using a passive circuit network to mimic an electrochemical cell demonstrate that the device performs comparable to laboratory grade instrumentation with 0.3% and 0.5° magnitude and phase error, respectively, over a 17 Hz–17 kHz frequency range. The measured power consumption is 2.5 mW with a dynamic range of 60 dB. This platform was verified by monitoring the real-time formation of a NeutrAvidin self-assembled monolayer on a gold electrode demonstrating the potential for POC diagnostics.

A multitechnique reconfigurable electrochemical biosensor for integration into mobile technologies

This paper describes the design and validation of a reconfigurable, multitechnique electrochemical biosensor intended for direct integration into smartphone and wearable technologies to realize a portable platform for Point-of-Care health monitoring. The reconfigurable potentiostat is able to perform various electrochemical techniques (amperometric, potentiometric, and impedance spectroscopy) and interfaces with several types of interchangeable electrochemical sensors all with a minimal number of components. A prototype of the reconfigurable potentiostat module was developed with discrete components, characterized, and compared against benchtop equipment. To show feasibility as well as flexibility of the platform, the device was used to run pH measurements and a glucose assay with comparable performance.

Smartphone-Based pH Sensor for Home Monitoring of Pulmonary Exacerbations in Cystic Fibrosis

Currently, Cystic Fibrosis (CF) patients lack the ability to track their lung health at home, relying instead on doctor checkups leading to delayed treatment and lung damage. By leveraging the ubiquity of the smartphone to lower costs and increase portability, a smartphone-based peripheral pH measurement device was designed to attach directly to the headphone port to harvest power and communicate with a smartphone application. This platform was tested using prepared pH buffers and sputum samples from CF patients. The system matches within ~0.03 pH of a benchtop pH meter while fully powering itself and communicating with a Samsung Galaxy S3 smartphone paired with either a glass or Iridium Oxide (IrOx) electrode. The IrOx electrodes were found to have 25% higher sensitivity than the glass probes at the expense of larger drift and matrix sensitivity that can be addressed with proper calibration. The smartphone-based platform has been demonstrated as a portable replacement for laboratory pH meters, and supports both highly robust glass probes and the sensitive and miniature IrOx electrodes with calibration. This tool can enable more frequent pH sputum tracking for CF patients to help detect the onset of pulmonary exacerbation to provide timely and appropriate treatment before serious damage occurs.

A scalable high-density electrochemical biosensor array for parallelized point-of-care diagnostics

This paper describes the design and verification of a prototype high-density electrochemical biosensor array for miniaturizing and enabling portable diagnostics devices that require high parallelizability. The prototype consists of a low-leakage 16-channel bi-potentiostat capable of running an electrochemical technique known as coulostatic discharge that is scalable for use with high-density sensors. Custom electronics with leakage of less than 100 fA were designed to interface with custom 4×4 nano-feature sensor array chips. By using a reversible redox molecule pair, we verified both preliminary simulated and measurement results of our system to varying redox concentrations.

Live demonstration: A low-cost smartphone-based electrochemical biosensor for point-of-care diagnostics.

By 2015, there will be an estimated 2.03 billion smartphone users worldwide [1]. This wide spread availability of mobile computing has inspired a surge of peripheral devices that add health-oriented functionality to the smartphone, such as the iBGStar® blood glucose meter and the AliveCor® ECG monitor. By similarly leveraging the power and functionality of the smartphone, we have built an electronic module that, when plugged into the audio jack of a smartphone and combined with disposable test chips, creates a low-cost biosensor. The smartphone would control and power the module through the audio port and analyze the measured data sent back by the module. This portable molecular sensor is meant to augment or replace bulky diagnostic equipment usually confined to labs and enable numerous point-of-care (POC) applications, thereby improving the convenience and speed of medical diagnoses.

A 64×64 high-density redox amplified coulostatic discharge-based biosensor array in 180nm CMOS

This paper describes the design of a high-density 4,096-pixel electrochemical biosensor array in 180nm CMOS for biomedical applications that require multiple analyte detection from small (5μL) samples. Each pixel of the array contains an exposed 45×45μm2 interdigitated micro-electrode surrounded by a ∼9pL nanowell fabricated using only a standard CMOS process along with a simple electroless gold plating procedure without the need for further post processing. Directly underneath each transducer is a complete ultra-low-leakage (sub-fA) readout circuitry, which leverages the Coulostatic Discharge sensing technique and interdigitated electrode (IDE) geometry to minimize both the complexity and overall size of the array. By evaluating IDE designs with different feature sizes (2–5μm), an average maximum amplification factor of 10.5x was achieved using redox cycling coupled with the higher collection efficiency of trenches formed from opening the passivation. The arrays sensor density is comparable to or better than state-of-the-art sensor arrays, all without augmenting the sensors with additional materials or structures. Using the array, detection of anti-Rubella is demonstrated as progress towards a complete vaccination panel.