New technology provides unprecedented insights for fever diagnostics

A revolutionary label-free technology that can detect the precise causes of fever has the potential to reduce antibiotic misuse, improve patient treatment of fever, and reduce financial burdens on healthcare systems.

CellFACE is currently in development and aims to develop cutting-edge point-of-care label-free imaging flow cytometry for accurate fever diagnosis, with the primary goal of distinguishing between bacterial and viral fever.

In this guest editorial, Dr. Komal Kumar Javarappa provides insights into this cutting-edge technology and its potential to revolutionize fever diagnostics and patient care. Dr. Komal Kumar Javarappa is a translational scientist at TUMCREATE under the supervision of Prof. Oliver Hayden, PhD, lead PI, TUM Schools CIT and Medicine, TranslaTUM, and Prof. Percy Knowlle, affiliated with the TUM School of Medicine in Germany. TUMCREATE is the Technical University of Munich's (TUM) interdisciplinary research platform at the Singapore Campus for Research Excellence and Technological Enterprise (CREATE), Singapore.

A new gold standard for fever diagnostics

CellFACE is a novel advancement in the field of high-throughput label-free point-of-care imaging-based flow cytometry. Its primary objective is to characterize and quantify blood biomarkers for the purpose of diagnosing and prognosticating fever-related conditions.

Current diagnostic techniques for fever are inadequate for quickly categorizing patients, which can result in increased expenses related to diagnosis and insufficient allocation of clinical resources. Hematological tests involving the examination of blood cell aggregates have the potential to aid in the diagnosis of fever. However, it is important to note that these tests are not yet accessible in standard clinical practice.

The CellFACE platform aims to enhance the detectability of elusive biomarkers by using a standardized and integrated methodology that leverages microfluidic cell fractionation and quantitative phase imaging techniques. The utilization of the CellFACE biomarker panel is anticipated to expedite the identification of accurate diagnoses for fever, while also furnishing biomarkers that may be used for prognostic purposes and monitoring the effectiveness of therapy.

The CellFACE system aims to detect and analyze blood biomarkers, namely platelet-platelet aggregates, platelet-leukocyte aggregates, and leukocyte-leukocyte aggregates. CellFACE utilizes artificial intelligence methods for the analysis of data and the conduct of prognostic longitudinal clinical diagnostic studies, with the aim of showcasing its potential use in clinical decision-making.

A multifaceted asset to patient care

CellFACE has the potential to facilitate the precise identification of fever caused by viral, bacterial, and non-infectious aetiologies. Additionally, this technology may provide valuable biomarkers for prognostication and monitoring the effectiveness of treatment strategies. The implementation of CellFACE technology is expected to bring about significant advancements in patient care. These advancements encompass a wide range of benefits, including enhanced antimicrobial stewardship and the prevention of unnecessary hospital admissions in cases where diagnosis is uncertain.

Moreover, the technology is anticipated to contribute to cost savings by expediting investigations and facilitating the rapid identification of the underlying causes of fever. Ultimately, CellFACE technology is expected to result in reduced morbidity and mortality rates. The use of CellFACE technology in the health care system has significant potential in terms of expediting diagnostic assessments, managing scarce resources, ensuring safety, and making substantial contributions to global health.

CellFACE is a promising platform for next-generation hematology analyzers to extend a complete blood count and leukocyte differentiation with cell function information based on deep analysis of cell aggregate compositions. This way, accurate host response due to inflammation and infection can support clinicians in early prognosis, prediction, and monitoring, patient logistics, and minimizing complications to improve patient outcomes.

The current complexities of fever diagnosis

Fever is a highly prevalent illness encountered in emergency departments, posing a significant diagnostic challenge for clinicians. Accurately identifying the precise cause fever is complex due to the numerous possible etiologies, including infectious (viral, bacterial, fungal) and non-infectious (inflammation, malignancy, autoimmunity) origins.

In order to accurately detect fever, it is necessary to do a number of tests, including complete blood count, differential leukocyte count, microscopic inspection, and blood culture. Each of these techniques offers just a limited perspective on the condition, requires a time frame of several days to weeks for obtaining findings, and is not economically efficient. Frequent occurrences include superfluous hospitalizations, unwarranted use of antibiotics, and inefficient utilization of clinical resources. The precise identification of fever may lead to a reduction in both mortality and morbidity rates. However, the proper identification of fever poses a significant challenge.

The current risk assessment methodologies exhibit inadequacies, hence presenting challenges in the early detection and prognosis of fever treatment. Patients exhibiting functional hematological indicators associated with immune system function, hemostasis, and organ function may be readily diagnosed. The current treatment tools used in clinical settings conceal these biological indicators.

The use of a quick diagnostic assessment and precision treatment tool has significant importance in effectively managing limited resources within global health care systems.

Blood cell aggregate analysis allows deeper insight

CellFACE utilizes quantitative phase imaging techniques that do not need sample preparation, since it is able to derive substantial contrast from the optical phase disparity of intracellular organelles and the associated morphological data. It operates without the need for labels or reagents and is capable of analyzing cells in a high throughput manner. This solution exhibits a high level of robustness and cost-effectiveness. The CellFACE technology has the capability to distinguish between bacterial and viral fevers by analyzing blood cell aggregates, namely platelet-platelet, platelet-leukocyte, and leukocyte-leukocyte aggregates.

The hurdles from development to implementation

There are many challenges that must be addressed prior to the development and widespread deployment of CellFACE technology. Most of the problems have been successfully overcome, particularly in regard to the recruitment of patients exhibiting fever for preclinical research. The study necessitates the acquisition of blood samples at various time intervals, sometimes encountering patient noncompliance subsequent to the first-time interval.

The examination of samples in CellFACE technology is a straightforward process, since it only takes a small volume of less than 15 to 20 µL. This is due to the label-free nature of the technology. One of the most formidable aspects lies in the discernment of blood cell aggregates via the use of artificial intelligence (AI). Currently, the CellFACE team are training the algorithm by using artificial aggregates. The objective is to enable the AI system to aid in the detection of aggregates inside clinical samples. The CellFACE team hope this workflow solution for blood cell analysis will ultimately improve acute care diagnostics once implemented into healthcare settings.

Learn more about the CellFACE project>>