Disposable Paper-on-CMOS Platform for Real-Time Simultaneous Detection of Metabolites

Abstract

Objective: Early stage diagnosis of sepsis without overburdening health services is essential to improving patient outcomes. Methods: A fast and simple-to-use platform that combines an integrated circuit with paper microfluidics for simultaneous detection of multiple-metabolites appropriate for diagnostics was presented. Paper based sensors are a primary candidate for widespread deployment of diagnostic or test devices. However, the majority of devices today use a simple paper strip to detect a single marker using the reflectance of light. However, for many diseases such as sepsis, one biomarker is not sufficient to make a unique diagnosis. In this work multiple measurements are made on patterned paper simultaneously. Using laser ablation to fabricate microfluidic channels on paper provides a flexible and direct approach for mass manufacture of disposable paper strips. A reusable photodiode array on a complementary metal oxide semiconductor chip is used as the transducer. Results: The system measures changes in optical absorbance in the paper to achieve a cost-effective and easily implemented system that is capable of multiple simultaneous assays. Potential sepsis metabolite biomarkers glucose and lactate have been studied and quantified with the platform, achieving sensitivity within the physiological range in human serum. Conclusion: We have detailed a disposable paper-based CMOS photodiode sensor platform for real-time simultaneous detection of metabolites for diseases such as sepsis. Significance: A combination of a low-cost paper strip with microfluidic channels and a sensitive CMOS photodiode sensor array makes our platform a robust portable and inexpensive

Recent Advances in Bedside Device-Based Early Detection of Sepsis

“…Hu et al adapted an existing concept, a disposable paper system as is used in the rapid evaluation of blood glucose levels in patients with diabetes mellitus, to evaluate blood lactate levels; however, the limits of detection were relatively higher than biomarker studies. 34 Nevertheless, the concept is excellent and the disposable paper system has proven utility in the management of diabetes, indicating that it could be easily translatable as a bedside screening measure in emergency departments for the early recognition of sepsis. Additional screening could be completed on an as-needed basis per admitted patients' condition.…”

“…In 2019, Hu et al developed a disposable paper system similar to that used in glucose monitors for measuring the conversion of lactate and glucose to their oxidized form. 34 Their device utilized a sensor that measured light emitting diode light absorption after passing through the sample. The chromatography paper contained three channels for independent evaluation of lactate and glucose as well as a control that contained glutamate.…”

Leukocyte Esterase Strip Quantitative Detection Based on RGB Photometry is a Probable Method to Diagnose Periprosthetic Joint Infection: An Exploratory Study

“…18,19 In recent years, complementary metal oxide semiconductor (CMOS) technology was introduced into various strip tests. [20][21][22] Oyaert et al conducted a series of studies on automatic dry chemical analysis (on a Sysmex UC-3500 urinary test strip reader) in combination with CMOS technology. Their results showed that the results of LE strips were quantifiable and could be mutually verified with leukocyte counts, which offered a feasible way to achieve quantitative detection of LE strips.…”

Micromolar Metabolite Measurement in an Electronically Multiplexed Format

“…The size of the chip was 3.4 mm x 3.6 mm. The CMOS chip has been fully characterized in previous works [28]- [31]. The chip required wire bonding for use.…”