Optofluidic Sensor for Inline Hemolysis Detection on Whole Blood

Abstract

Hemolysis is the rupture of red blood cells and constitutes the most common reason for unsuitable blood samples in the clinic. To detect hemolysis, one has to separate the hemoglobin in blood plasma from that in red blood cells. However, current methods entail centrifugation for cell-plasma separation, which is complex, time-consuming, and not easy to integrate into point-of-care (PoC) systems. Here, we demonstrate an optofluidic sensor composed of nanofilters on an optical waveguide, which enables evanescent-wave absorption measurement of hemoglobin in plasma with the capability of real-time inline detection on whole blood without extra sample preparation like centrifugation. Long-term testing with inline integration in a modified, commercial blood gas analyzer shows high reliability and repeatability of the measurements even with the presence of interference from bilirubin. We envision that the present work has large potential in improving diagnosis quality by enabling PoC hemolysis detection in blood gas analyzers and can also lend unique sensing capabilities to other applications dealing with complex turbid media.

In situ sensors for flow reactors – a review

“…Inline measurements do not require the presence of senior operators due to minor mistakes introduced, and they typically have good repeatability if precisely automated machines are employed. 18 Like inline measurements, online measurements also do not require the transfer of the samples in the process. The flow stream is regularly sampled only for representatively independent samples that are of high importance for progress identification.…”

Perspectives on smart stents with sensors: From conventional permanent to novel bioabsorbable smart stent technologies

“…Various types of F I G U R E 2 (a) Schematic drawing of an optofluidic haemolysis sensor with nanofilters consisting of an array of nanowells for cell/plasma separation, which allow the passage of small molecules like haemoglobin through it while blocking large components such as erythrocytes, platelets and other blood cells. Reprinted from Zhou et al (2018), with permission from American Chemical Society. (b) Highly sensitive 3D nanoplasmonic sensors with microposts with high refractive index sensitivity, which can separate and detect filopodia from cell bodies.…”

“…Since NO is gaseous signalling molecule indicating re‐endothelialization (Bedair, ElNaggar, Joung, & Han, 2017; Li et al, 2018), detection of insufficient NO generation can be a potential sensing strategy. Recently developed optofluidic sensor with a nanofilter comprising of an array of nanowells to detect haemolysis by separating haemoglobin (Zhou et al, 2018) and 3D nanoplasmonic biosensor to detect cell filopodia (Zhu, Eldeeb, & Pang, 2020) represents prospective approaches in this direction (Figure 2(a,b)).…”

Multifunctional waveguide interferometer sensor: simultaneous detection of refraction and absorption with size-exclusion function

“…The fabrication process is adapted from our previous work [22]. A process flow is illustrated in Fig.…”

“…Here, we address this issue and present a sensor that is able to detect real and imaginary part of the refractive index at the same time using a Young interferometer. Furthermore, we added size-exclusion sensing functionalities, which has been demonstrated in our previous work for detection of hemolysis in whole blood [22]. The multi-functionality can significantly expand the applicability of the sensor in to areas dealing with complex turbid medium.…”