Elsevier

Microelectronic Engineering

Volume 132, 25 January 2015, Pages 46-57
Microelectronic Engineering

Review Article
Point-of-care testing (POCT) diagnostic systems using microfluidic lab-on-a-chip technologies

https://doi.org/10.1016/j.mee.2014.09.024Get rights and content

Highlights

  • Introduction on POCT diagnostic systems and their requirements in general.

  • Review on demonstrated and commercially available POCT diagnostic systems.

  • Discussion on current limitations and future prospects of POCT diagnostic systems.

Abstract

Point-of-care testing (POCT) is necessary to provide a rapid diagnostic result for a prompt on-site diagnosis and treatment. A quick analysis time and high sensitivity, with a sample-to-answer format, are the most important features for current POCT diagnostic systems. Microfluidic lab-on-a-chip technologies have been considered as one of the promising solutions that can meet the requirement of the POCT since they can miniaturize and integrate most of the functional modules used in central laboratories into a small chip. This review covers recent advances in POCT technologies with an emphasis on demonstrated and commercially available POCT diagnostic systems with laboratory quality using microfluidic lab-on-a-chip technologies. As working principles and required functional modules depend on target analytes, we categorize the applications of the POCT diagnostic systems according to the analyte types such as proteins, cells, nucleic acids, and metabolites. In each analyte category, detection methods, configuration of POCT lab-on-a-chip modules, and advantages and disadvantages of POCT systems are reviewed and discussed along with future prospects.

Introduction

Point-of-care testing (POCT) diagnostic systems are instruments that can rapidly provide in vitro diagnostic results by non-trained personnel at a patient site in the physician’s office, the field, the home, an ambulance, or a hospital [1]. Traditionally, and still today, diagnostic tests are usually performed at central laboratories equipped with bench-top analyzers and operated by trained personnel. As a result, patients usually have to wait for days to receive their test results. Thus, there has been a growing need to provide diagnostic results at the point of care, for prompt treatment of acute diseases such as acute myocardial infarction and for home-care diagnostics such as diabetes monitoring.

Rigorous requirements are set for POCT diagnostic systems in order to satisfy the needs for POCT as follows: (a) rapid test results to allow patients to receive follow-up treatment at the point-of-care; (b) accurate, quantitative results that could be comparable to the ones from bench-top analyzers at central laboratories, in order to avoid false diagnostics; and (c) easy-to-use systems that could be run by a non-expert, with minimum user interventions. In that sense, a “sample-to-answer” system is a desirable format because users only need to load a sample to the systems and then obtain the test results after pushing a start button as illustrated in Fig. 1.

Conventionally, the application of POCT systems has been limited to glucose-level test strips by an electrochemical detection method [2], [3], [4] and lateral-flow strips by immunoassay [5], [6] predominantly used for diabetes self-monitoring and home pregnancy tests, respectively. However, many POCT glucose measurement systems that are currently available on the market provide poor performance for tight glycemic control [7], [8]. Most conventional lateral-flow assays provide a qualitative answer, which is typically positive/negative (i.e., yes or no test) while suffering from numerous outliers [9] due to difficulties in achieving uniform dispersion of the sample to label and consistency of the flow rate [1], [10]. Due to the limited capability of conventional POCT systems, numerous new technologies have been explored to meet the requirements of POCT systems.

Microfluidics and lab-on-a-chip technologies have been especially spotlighted and extensively researched owing to the innate advantages, such as low sample and reagent volume, high capability of integration, and rapid reaction from small feature sizes [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25]. Additionally, POCT systems detect specific biomarkers from proteins, cells, nucleic acids, metabolites, and so on. Different classes of biomarkers require different diagnostic principles, assays, or operating systems. Thus, we will review and discuss the specific diagnostic principles or assays adopted for the microfluidics and lab chip-based POCT diagnostic systems in terms of their limitations and requirements for the specific target analyte.

Section snippets

Proteins

Proteins have been one of the major categories of POCT biomarkers as they often reveal the presence and/or status of certain diseases that commonly need to be diagnosed [26]. The most prevalent working principle in detecting target proteins is the immunoassay, which uses antigen–antibody binding reactions that lead to an analysis with high specificity and sensitivity, due to a unique recognition between antigen and antibody.

Compared to nucleic acid detection, which has to go through cell lysis,

Complete blood count

The counting of white blood cells (WBCs), red blood cells (RBCs), and platelets is important in clinical diagnostics because high or low numbers of specific cell types beyond normal ranges can indicate the presence and/or status of diseases or immunity. Although blood cell counting has been mainly processed by bench-top hematology analyzers, there have been numerous studies to count cells with microfluidics and lab chips.

Zhu et al. at UCLA counted red blood cells and white blood cells and

Nucleic acids

Nucleic acids exist in all living creatures and function in encoding, transmitting and expressing genetic information through their specific sequence, or the order of nucleotides within the nucleic acids. Therefore, detecting nucleic acids gives high sensitivity and specificity in diagnosing particular diseases. As it is necessary to obtain a large quantity of nucleic acids for the diagnosis, it is often more useful to generate multiple copies of a target from a single molecule of nucleic acid

Metabolites

Metabolites (glucose, urea nitrogen, creatinine, lactate, etc.) and ionic blood chemicals (sodium, potassium, chloride, etc.) have been used as biomarkers in revealing various body conditions such as diabetes, liver disease, and acid base homeostasis. Among them, glucose has been the most frequent biomarker for diagnosis and management of diabetes so that there are more than 40 commercial glucose biosensors, occupying more than 80% of the commercial biosensors [4].

The glucose monitoring system

POCT diagnostic systems in the developing world

Global health, especially in the developing world, has been of the utmost concern due to the high mortality rate from pandemic diseases such as HIV, TB, and malaria resulting from little or no medical infrastructure. In that sense, POCT diagnostic systems can greatly contribute to increasing the survival rate of infected patients and decreasing infection rate by early diagnosis of the diseases [122], [123], [124], [125], [126], [127], [128], [129], [130], [131]. Due to the urgent need and the

Concluding remarks

Microfluidic lab-on-a-chip technology has a unique characteristic of high surface area to volume ratio resulting in fast analysis time that enables point-of-care testing (POCT). It also has a potential to accomplish complex diagnostic assays, e.g. nucleic acid short tandem repeat fingerprinting, as a sample to answer format for POCT by integrating all the functional modules into a lab-on-a-chip. These advantages of the microfluidic lab-on-a-chip technology thus encouraged to have extensive

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