Micro-Engineered Devices for Point-of-Care Blood Clot Retraction Testing

Abstract

Blood coagulation is a critical hemostatic process that must be properly regulated to maintain the delicate balance between bleeding and clotting. Disorders of blood coagulation can expose patients to the risk of either bleeding disorders or thrombotic diseases. Coagulation diagnostics using whole blood is promising for the assessment of the complexity of the coagulation system and for global measurements of hemostasis. Despite the clinical values that existing whole blood coagulation tests have demonstrated, these systems have significant limitations that compromise their potential for point-of-care applications. Device miniaturization using micro-technology has the potential to provide assays with low blood consumption and high accuracy. However, previous works have either focused on developing tools for mechanistic study, or are too complex to be implemented for point-of-care applications.

This thesis aims to leverage advances in micro-technology and functional soft materials to develop miniaturized devices for clot retraction force measurements, providing accurate and reliable blood coagulation assays with potentials for point-of-care applications.

First, I designed a force-sensing device, named Miniaturized Hemoretractometer (mHRM), based on image acquisition and analysis to measure contraction force generated during blood clotting. This clot retraction force served as an indicator of coagulation functionality. I demonstrated that measurements generated from mHRM were consistent with previous works, under various conditions such as different temperatures and pro-/anti-coagulant treatments, which validates the concept of using mHRM as a tool for blood coagulation diagnostics.

Acquiring electrical signals instead of images could vastly simplify the instrumentation of mHRM. However, integrating conductive materials into soft elastomer (PDMS) was a challenge. To address this problem, I developed a method to coat carbon nanotubes (CNTs) on PDMS surface from CNT solutions, leveraging capillary action. I demonstrated that deposited CNT films had good uniformity and piezoresistivity, making them a promising candidate for the development of strain sensors. This aim contributed a novel and convenient method for solution-based CNT deposition.

Finally, I applied this CNT deposition method into the design of mHRM and developed a CNT strain sensor based mHRM (CNT-mHRM). I investigated the parameters that affected the sensitivity of CNT-mHRM devices and demonstrated that CNT-mHRM generated results that were consistent with image analysis based measurements. The utility of CNT-mHRM was further demonstrated by showing its capability of differentiating blood samples under pro- and anti-coagulation treatments. Thus, I demonstrated the potential of CNT-mHRM devices as a practical point-of-care tool for blood coagulation diagnostics.