Point of Care Diagnostics: Status and Future

Abstract

CONTENTSshould be inexpensive disposable chips or cartridges that include microfluidic features to provide or control sample preparation, flow rate, mixing with reagents, reaction time associated with binding events, filtration of nonanalytical components of the sample, separation of interfering agents and of multiple analytes, and an effective measurement capability. 4 POC diagnostics have been extensively reviewed in recent years, from the points of view of both use 5 and development. 6 The reviews have included coverage of micrototal analysis systems (μTAS), 7 miniaturized isothermal nucleic acid amplification 8 and molecular biological techniques for gene assay, 9 current and anticipated technology for POC infection diagnosis, 10 and microfluidic-based systems leading toward point-of-care detection of nucleic acids and proteins, 11 including multiplexing and labelfree methods. 12 Developments in this area include not only technology but also reliable measurement targets, which in some important areas remain elusive: progress toward viable point-ofcare protein biomarker measurements for cancer detection and diagnostics has been reviewed. 13 We review here the present status of POC diagnostics, emphasizing in particular the past 4 years, then extrapolate their progress into the future. Included are IVD tests for biochemical targets of all sorts relevant to human health, diagnosis, and therapy, as enumerated above. We begin with an overview of the different classes of bioanalytical targets. Then, after setting the context using the well-established glucose and pregnancy POC tests, recent progress in key enabling technologies is reviewed, including traditional and advanced lateral flow approaches, printing and laminating technologies, a range of microfluidic advances, progress in surface chemistry and the control of nonspecificbinding, and developments in labeled and label-free detection approaches. A number of specific innovative examples, in both commercial products and academic POC research, are presented, including assays based on binding to proteins, nucleic acids, and aptamers, with separate sections devoted to blood chemistry, coagulation, and whole cells. We close with trends and future perspectives.Why POC Diagnostics? Time POC measurements provide results rapidly, where needed, and often with major time savings: samples do not travel to a laboratory to await the attention of a skilled technician; results do not wait to be transmitted and collected. Rather, the doctor, nurse, care-giver, patient, or consumer initiates the test and receives the results on the spot. Inevitably this saves time, but speed must not be traded for accuracy or reliability. Figure 1. Idealized POC device. Adapted with permission from ref 6a.

Molecular-based Screening for Perinatal Group B Streptococcal Infection: Implications for Prevention and Therapy

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A microfluidic anti-Factor Xa assay device for point of care monitoring of anticoagulation therapy

“…In brief, absorbance and fluorescence measurements were performed in an Infinite M200 spectrophotometric microplate reader (Tecan Group Ltd, Männedorf, Switzerland). Plasma samples were spiked with 20 pharmacologically relevant concentrations (0-0.8 U/ml) of therapeutic anticoagulants. The fluorogenic assay was performed as previously described.…”

“…Further discussion on the optimization of substrate deposition can be found in the supplemental section S-2 Results and discussion. 20 …”

“…Arterial and venous thromboembolism remain two of the most 20 frequent causes of morbidity and mortality worldwide. 1 Blood clotting disorders such as these have long been treated using anticoagulant drugs such as warfarin and heparin, with newer, more predictable drugs such as factor Xa (FXa) and thrombin inhibitors now available.…”

“…Glass has always been favored for optical applications due to its excellent clarity. However, its 20 brittle nature results in processing and handling difficulties. 15 Other inorganic materials such as silicon and quartz are not ideal for disposable microfluidics due to high material and manufacturing costs.…”