Fully integrated wearable impedance cytometry platform on flexible circuit board with online smartphone readout

Abstract

We present a wearable microfluidic impedance cytometer implemented on a flexible circuit wristband with on-line smartphone readout for portable biomarker counting and analysis. The platform contains a standard polydimethylsiloxane (PDMS) microfluidic channel integrated on a wristband, and the circuitry on the wristband is composed of a custom analog lock-in amplification system, a microcontroller with an 8-bit analog-to-digital converter (ADC), and a Bluetooth module wirelessly paired with a smartphone. The lock-in amplification (LIA) system is implemented with a novel architecture which consists of the lock-in amplifier followed by a high-pass filter stage with DC offset subtraction, and a post-subtraction high gain stage enabling detection of particles as small as 2.8 μm using the 8-bit ADC. The Android smartphone application was used to initiate the system and for offline data-plotting and peak counting, and supports online data readout, analysis, and file management. The data is exportable to researchers and medical professionals for in-depth analysis and remote health monitoring. The system, including the microfluidic sensor, microcontroller, and Bluetooth module all fit on the wristband with a footprint of less than 80 cm². We demonstrate the ability of the system to obtain generalized blood cell counts; however the system can be applied to a wide variety of biomarkers by interchanging the standard microfluidic channel with microfluidic channels designed for biomarker isolation.

Fig. 1

Custom-built analog architecture for impedance cytometry with off-the shelf hardware. a System block diagram of cytometer-readout architecture. b Lateral view of microfluidic channel, where R represents channel resistance, ΔR is variable resistance from particle flow, and C_D is double-layer capacitance

Fig. 2

Wearable cytometry system on flexible PCB with integrated microfluidic PDMS chip, microcontroller, and BLE readout to smartphone (not shown)

Fig. 3

Top view of 30 μm microfluidic PDMS channel pore with sheep blood cells shown flowing across electrodes

Fig. 4

Screenshots from our custom Android application of a splash screen b live data plot and peak count with buttons to initiate sampling, save the measurement, and plot history data

Fig. 5

Screenshots from video and cellphone recorded during experiment, combining the optical microscopic view of the sensor and the digital data plotted on the smartphone as human RBC flows past the electrodes from a–d

Fig. 6

Data exported from smartphone application, measured through wearable LIA with PBS only a and 3 μm polystyrene beads b and sheep blood cells flowing through 50 μm PDMS channel c and human blood cells flowing through 30 μm channel for 30 s d. e Results from figure c data shown on smartphone application

Fig. 7

Selected data plotted to MATLAB from 10-minute experiment with human blood cells flowing through a 30-μm-wide channel during an experiment with a duration of 10 min a without modification b after applying a Butterworth band-pass filter using the Signal Processing Toolbox. The red dashed line represents the negative threshold voltage of −0.2 V, and the green dashed line appears for peaks which included in the final count

Fig. 8

Total optical microscopic count vs. digital system count from 10-minute experiment with human blood cells