Integrating printed microfluidics with silicon photomultipliers for miniaturised and highly sensitive ATP bioluminescence detection

Abstract

Bioluminescence has been widely used for important biosensing applications such as the measurement of adenosine triphosphate (ATP), the energy unit in biological systems and an indicator of vital processes. The current technology for detection is mainly based on large equipment such as readers and imaging systems, which require intensive and time-consuming procedures. A miniaturised bioluminescence sensing system, which would allow sensitive and continuous monitoring of ATP, with an integrated and low-cost disposable microfluidic chamber for handling of biological samples, is highly desirable. Here, we report the design, fabrication and testing of 3D printed microfluidics chips coupled with silicon photomultipliers (SiPMs) for high sensitive real-time ATP detection. The 3D microfluidic chip reduces reactant consumption and facilitates solution delivery close to the SiPM to increase the detection efficiency. Our system detects ATP with a limit of detection (LoD) of 8nM and an analytical dynamic range between 15nM and 1µM, showing a stability error of 3%, and a reproducibility error below of 20%. We demonstrate the dynamic monitoring of ATP in a continuous-flow system exhibiting a fast response time, ~4s, and a full recovery to the baseline level within 17s. Moreover, the SiPM-based bioluminescence sensing system shows a similar analytical dynamic range for ATP detection to that of a full-size PerkinElmer laboratory luminescence reader.

Biosensors in Monitoring Water Quality and Safety: An Example of a Miniaturizable Whole-Cell Based Sensor for Hg2+ Optical Detection in Water

“…The sensor is composed by a cuvette containing a suspension of the E. coli reporter bacteria, and a micro-sized silicon photomultiplier, SiPM, detector, both integrated in a miniaturized dark box. The SiPM is an optical detector widely used in biosensing applications for healthcare and environmental monitoring [54][55][56][57].…”

Epitaxial Graphene Sensors Combined with 3D Printed Microfluidic Chip for Heavy Metals Detection

“…Both microfluidic chips, which include inlet and outlet ports with an internal radius of 500 µm, were designed using Autodesk Inventor Fusion 360 ® CAD software (version 2.0.5044) and printed by a Form 1 + 3D printer (FormLabs) with a proprietary resin Clear Type 02. The resin includes different proportions of modified acrylate and acrylate oligomer, epoxy monomer, acrylate monomer, photo initiator and additives as the principal components [7,8]. A 2601A Keithley Source Meter was used to bias the sensor ant to collect the output signal.…”

3D printing for chemical, pharmaceutical and biological applications

“…97,98 Pertinently, the developments of these 3D printed systems have enabled the pharmacokinetic profiling of candidate molecules, 99 whilst also generating novel physiological data surrounding pathological conditions. 100 Other 3D printed bioanalytic devices have also been reported, such as miniaturised adenosine triphosphate (ATP) bioluminescence sensing, 101 clinically relevant whole organ biomarker profiling, 102 and electrochemical influenza virus detection. 103 Such technological developments hold significant promise within the drug discovery process.…”