Acoustic probing for rapid sickle cell disease screening using microfluidic biomarkers

Early diagnosis of sickle cell disease remains a major challenge, particularly in low-resource settings where access to centralized laboratories is limited. Conventional diagnostic techniques such as hemoglobin electrophoresis or HPLC are accurate but require expensive equipment, trained personnel, and long processing times. This gap has driven the search for rapid, low-cost screening tools that can operate at the point of care and provide clinically meaningful information from minimal blood volumes; a suitable for microfluidic research. 

In this study, the authors introduce an acoustic microfluidic chip that identifies sickle cell disease using two previously unexplored biomarkers related to blood thermal responses. Their solution relies on surface acoustic waves applied to a simple lab-on-a-chip device to probe red blood cell membrane stability and plasma protein concentration directly from small volumes of whole blood or plasma.

“Here, we have discovered new biomarkers for SCD diagnosis, enabled by acoustic probing: combining acoustic radiation force and acoustic heating. We apply surface acoustic waves (SAWs) to lyse RBCs and induce protein denaturation and aggregation on-chip.”, the authors explained. 

The microfluidic device consists of a PDMS microchannel that is microfabricated by bonding to a lithium niobate substrate patterned with interdigital transducers. When radiofrequency signals are applied, standing surface acoustic waves form inside the microfluidic channel. These waves simultaneously generate acoustic radiation forces that organize cells and proteins into pressure nodes and acoustic heating that raises the temperature of the sample in a controlled manner. Whole blood samples first undergo red blood cell alignment in the microfluidic device, followed by cell lysis as temperature increases, and finally protein denaturation and aggregation. Plasma samples bypass the cell-related steps and proceed directly to protein aggregation. The entire microfluidic assay uses less than a few microliters of sample and completes in under two minutes.

Using whole blood, the authors show that the temperature at which red blood cells lyse serves as a marker of membrane stability. Samples from healthy donors lysed at lower temperatures, while samples from individuals with sickle cell disease required higher temperatures, reflecting increased membrane rigidity associated with sickled cells. Importantly, the method was sensitive enough to distinguish not only healthy samples from severe disease, but also samples from patients who had undergone transfusion exchange and therefore had milder phenotypes. Receiver operating characteristic analysis demonstrated strong diagnostic performance, with perfect separation between healthy controls and untreated sickle cell disease in this cohort.

In parallel, plasma protein concentration was assessed by measuring the extent of protein precipitation during acoustic heating. Plasma from sickle cell disease donors showed significantly greater protein aggregation than healthy plasma. Independent biochemical assays confirmed that total protein levels were elevated in diseased samples, largely driven by increased globulin concentrations. This acoustic readout therefore provides a second, complementary biomarker that can be obtained using the same microfluidic device and operating protocol.

Together, these results demonstrate that acoustic probing can extract clinically relevant information from blood without labels, antibodies, or complex sample preparation. By combining red blood cell membrane stability and plasma protein concentration into a single score, the authors further improved diagnostic robustness and reduced the impact of outliers. The simplicity of the microfluidic chip design, low power requirements, and short assay time suggest strong potential for point-of-care screening, particularly for early identification of sickle cell disease in settings where conventional diagnostics are impractical.

“This acoustic method also shows potential for broader applicability to study the role that cellular thermal stability and protein concentration levels may play in other blood-based disorders. Overall, our acoustically enabled biomarkers show promise for cheap, rapid, and accurate hematology in POC settings.”, the authors concluded.

Figures are reproduced from N. Sridhar, M. Song, M. H. B. Stowell, K. L. Hassell and X. Ding, Lab Chip, 2026, Advance Article , DOI: 10.1039/D4LC00847B under a  Creative Commons Attribution 3.0 Unported Licence.

Read the original article: Acoustic probing of new biomarkers for rapid sickle cell disease screening

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