A critical insight into the development pipeline of microfluidic immunoassay devices for the sensitive quantitation of protein biomarkers at the point of care. Issue 6 (20th February 2017)

• Record Type: Journal Article
• Authors: Barbosa, Ana I.; Reis, Nuno M.
• Is Part Of: Analyst. Volume 142:Issue 6(2017)
• Page Start: 858
• Page End: 882
• Publication Date: 2017-02-20
• Subjects: Chemistry, Analytic -- Periodicals; 543
• DOI: 10.1039/c6an02445a
• Languages: English
• ISSNs: 0003-2654

Abstract

Abstract : A critical review on the development of microfluidic tests capable of the high-sensitivity measurement of protein biomarkers at the point-of-care. Abstract : The latest clinical procedures for the timely and cost-effective diagnosis of chronic and acute clinical conditions, such as cardiovascular diseases, cancer, chronic respiratory diseases, diabetes or sepsis ( i.e. the biggest causes of death worldwide), involve the quantitation of specific protein biomarkers released into the blood stream or other physiological fluids ( e.g. urine or saliva). The clinical thresholds are usually in the femtomolar to picolomar range, and consequently the measurement of these protein biomarkers heavily relies on highly sophisticated, bulky and automated equipment in centralised pathology laboratories. The first microfluidic devices capable of measuring protein biomarkers in miniaturised immunoassays were presented nearly two decades ago and promised to revolutionise point-of-care (POC) testing by offering unmatched sensitivity and automation in a compact POC format; however, the development and adoption of microfluidic protein biomarker tests has fallen behind expectations. This review presents a detailed critical overview into the pipeline of microfluidic devices developed in the period 2005–2016 capable of measuring protein biomarkers from the pM to fM range in formats compatible with POC testing, with a particular focus on the use of affordable microfluidic materials and compact low-cost signal interrogation. The integration of these two important features (essential unique selling points for the successful microfluidic diagnostic products) has been missed in previous review articles and explain the poor adoption of microfluidic technologies in this field. Most current miniaturised devices compromise either on the affordability, compactness and/or performance of the test, making current tests unsuitable for the POC measurement of protein biomarkers. Seven core technical areas, including (i) the selected strategy for antibody immobilisation, (ii) the surface area and surface-area-to-volume ratio, (iii) surface passivation, (iv) the biological matrix interference, (v) fluid control, (vi) the signal detection modes and (vii) the affordability of the manufacturing process and detection system, were identified as the key to the effective development of a sensitive and affordable microfluidic protein biomarker POC test.