A Point-of-Care Device for Molecular Diagnosis Based on CMOS SPAD Detectors with Integrated Microfluidics

Joan Canals; Nil Franch; Oscar Alonso; Anna Vilà; Angel Diéguez

doi:10.3390/s19030445

A Point-of-Care Device for Molecular Diagnosis Based on CMOS SPAD Detectors with Integrated Microfluidics

Sensors (Basel). 2019 Jan 22;19(3):445. doi: 10.3390/s19030445.

Authors

Joan Canals¹, Nil Franch², Oscar Alonso³, Anna Vilà⁴, Angel Diéguez⁵

Affiliations

¹ Electronic and Biomedical Engineering Department, University of Barcelona, 08028 Barcelona, Spain. jcanals@el.ub.edu.
² Electronic and Biomedical Engineering Department, University of Barcelona, 08028 Barcelona, Spain. nfranch@el.ub.edu.
³ Electronic and Biomedical Engineering Department, University of Barcelona, 08028 Barcelona, Spain. oalonso@el.ub.edu.
⁴ Electronic and Biomedical Engineering Department, University of Barcelona, 08028 Barcelona, Spain. avila@el.ub.edu.
⁵ Electronic and Biomedical Engineering Department, University of Barcelona, 08028 Barcelona, Spain. adieguez@el.ub.edu.

Abstract

We describe the integration of techniques and technologies to develop a Point-of-Care for molecular diagnosis PoC-MD, based on a fluorescence lifetime measurement. Our PoC-MD is a low-cost, simple, fast, and easy-to-use general-purpose platform, aimed at carrying out fast diagnostics test through label detection of a variety of biomarkers. It is based on a 1-D array of 10 ultra-sensitive Single-Photon Avalanche Diode (SPAD) detectors made in a 0.18 μm High-Voltage Complementary Metal Oxide Semiconductor (HV-CMOS) technology. A custom microfluidic polydimethylsiloxane cartridge to insert the sample is straightforwardly positioned on top of the SPAD array without any alignment procedure with the SPAD array. Moreover, the proximity between the sample and the gate-operated SPAD sensor makes unnecessary any lens or optical filters to detect the fluorescence for long lifetime fluorescent dyes, such as quantum dots. Additionally, the use of a low-cost laser diode as pulsed excitation source and a Field-Programmable Gate Array (FPGA) to implement the control and processing electronics, makes the device flexible and easy to adapt to the target label molecule by only changing the laser diode. Using this device, reliable and sensitive real-time proof-of-concept fluorescence lifetime measurement of quantum dot Qdot^TM 605 streptavidin conjugate is demonstrated.

Keywords: CMOS; fluorescence lifetime; laser diode; low-cost; microfluidics; molecular diagnosis; point-of-care; single-photon avalanche diode.

MeSH terms

Equipment Design
Fluorescence
Fluorescent Dyes / chemistry
Microfluidics*
Molecular Diagnostic Techniques / instrumentation*
Oxides
Photons*
Point-of-Care Testing*
Semiconductors*

Substances

Fluorescent Dyes
Oxides

Grants and funding

737089/Horizon 2020 Framework Programme