Emerging Microfluidic Devices for Sample Preparation of Undiluted Whole Blood to Enable the Detection of Biomarkers

Abstract

Blood testing allows for diagnosis and monitoring of numerous conditions and illnesses; it forms an essential pillar of the health industry that continues to grow in market value. Due to the complex physical and biological nature of blood, samples must be carefully collected and prepared to obtain accurate and reliable analysis results with minimal background signal. Examples of common sample preparation steps include dilutions, plasma separation, cell lysis, and nucleic acid extraction and isolation, which are time-consuming and can introduce risks of sample cross-contamination or pathogen exposure to laboratory staff. Moreover, the reagents and equipment needed can be costly and difficult to obtain in point-of-care or resource-limited settings. Microfluidic devices can perform sample preparation steps in a simpler, faster, and more affordable manner. Devices can be carried to areas that are difficult to access or that do not have the resources necessary. Although many microfluidic devices have been developed in the last 5 years, few were designed for the use of undiluted whole blood as a starting point, which eliminates the need for blood dilution and minimizes blood sample preparation. This review will first provide a short summary on blood properties and blood samples typically used for analysis, before delving into innovative advances in microfluidic devices over the last 5 years that address the hurdles of blood sample preparation. The devices will be categorized by application and the type of blood sample used. The final section focuses on devices for the detection of intracellular nucleic acids, because these require more extensive sample preparation steps, and the challenges involved in adapting this technology and potential improvements are discussed.

Stabilizing and Accelerating Secondary Flow in Ultralong Spiral Channel for High-Throughput Cell Manipulation

“…Outlet 3 was able to increase the concentration of blood cells threefold, from 5.78 × 10 8 to 1.73 × 10 9 cells/mL (Figure D). Meanwhile, the number of cells per ml exported from outlet 1 decreased by a factor of 10,000, which is technically over the current microfluidic chips. − The study also found that the separation effect was better with higher dilutions (Figure E).…”

Music Box-Inspired Semi-Automatic Hematocrit Validation Device

“…The system we have developed can be used for immediate diagnosis, home monitoring at a very low cost, and also applied in areas lacking medical resources and trained technicians (Table S2). Not only can it replace the microhematocrit centrifuge, we expect this device can be expanded to other clinical diagnostic applications with this modality or its modifier in monitoring other hematological health conditions. − …”

High-Throughput Blood Plasma Extraction in a Dimension-Confined Double-Spiral Channel

“…Furthermore, it plays a crucial role in a variety of illnesses, including malaria, sickle cell anemia, and diabetes. , The intricate composition of blood encompasses plasma, erythrocytes (red blood cells), leukocytes (white blood cells), and thrombocytes (platelets). Erythrocytes constitute roughly 45% of the total blood volume, whereas leukocytes and platelets combined contribute to a comparatively minimal 1%. , 55% of the blood volume is constituted by plasma, a pale-yellow liquid. Its composition predominantly includes water, accounting for approximately 91%.…”

“…Its composition predominantly includes water, accounting for approximately 91%. Proteins contribute to 7% of the plasma content, while the residual 2% consists of inorganic ions and various other organic substances. − Biomarkers within human plasma, such as proteins, electrolytes, urea, and glucose, provide a comprehensive overview of the body’s physiological state. − With the advancements in the study of plasma proteomics, transcriptomics, and metabolomics, these biological markers play a significant analytical role in the diagnosis of various diseases. − Similarly, the detection of antibodies, foreign nucleic acids, and antigens in blood plasma can be of great help in diagnosing serious infectious diseases, including Ebola Hemorrhagic Fever, Acquired Immune Deficiency Syndrome (AIDS), and the recent Coronavirus Pneumonia outbreak. − However, the excessive presence of blood cells, especially platelets, can significantly disrupt the accurate identification of desired biomarkers in the bloodstream. Therefore, the process of extracting purer plasma by eliminating blood cells emerges as an imperative step. , …”