- New microfluidic device that
measures neutrophil migration patterns in sick patients found to
accurately predict onset of sepsis with 95 percent accuracy
- Current methods of diagnosis of
sepsis remain imprecise resulting in missed or delayed diagnosis
- Sepsis is diagnosed in over a
million patients in the US each year and is associated with high death
microfluidic device developed by
scientists at the Massachusetts General Hospital
(MGH) accurately measures
migration patterns of neutrophils (a type of white blood cell important in the
immune response). Measurement of neutrophil motility in a single drop of blood
has been found to be able to predict
patients at risk of developing sepsis
so that appropriate treatment
measures can be instituted to prevent its occurrence.
findings of the study appear in the journal Nature Biomedical Engineering
‘Analyzing neutrophil migration and motility patterns could be potential tool in the early diagnosis and treatment of sepsis resulting in a much more favorable patient outcome’
found that neutrophils from sepsis patients exhibit specific spontaneous
migration patterns when tested in whole blood samples,"
Ellett, PhD, a postdoctoral fellow in the BioMEMS Resource Center in
the MGH Department of Surgery, lead author of the study.
sepsis, factors present in the plasma of
these patients induce neutrophils to migrate spontaneously
when placed into
the mazes of our microfluidic device, and we were able to identify migration
patterns specific to sepsis."
Reason for Study
function has long been known to be an important reason for occurrence of
there are currently no methods to
accurately measure neutrophil
function to predict or diagnose sepsis
newly designed microfluidic device hopes to overcome this critical gap
enable precise and early diagnosis and treatment of sepsis which would vastly
improve patient prognosis and outcome.
Methods of the Study
Irimia, MD, PhD, associate director of the
BioMEMS Resource Center and senior author of the current study had earlier led a study in 2014 which found that measuring movement
patterns of isolated neutrophils, (including
rapid, spontaneous motion not stimulated by a chemical attractant), could
accurately predict those patients who were likely to develop sepsis.
- The authors of the current study
believed that the results of
earlier study (2014) on isolated neutrophils could be further validated in
blood samples obtained from seriously ill patients.
- Blood samples obtained from 23 patients under intensive care at
various periods of hospitalization were assessed for neutrophil motility
patterns using the special micro
- The newly developed microfluidic device - around 5
millimeters in diameter, is made
up of a central chamber surrounded
by filters that prevent red blood cells and other
blood components from passing through
- Only neutrophils can pass through
the filters and reach a maze of
channels within which their motility patterns can be studied
- The research team identified and measured five
neutrophil parameters, namely, the number of neutrophils, their
movements within the channels, the time spent remaining immobile, reverse
movement back into the central chamber, and the average distance migrated.
five parameters were used to establish a
to predict those
patients who were at risk for developing sepsis or had sepsis.
- The initial observations were reconfirmed by testing samples from a
separate group of 19 patients from another ICU; results showed more
than 95 percent accuracy in identifying patients at risk of or having
Thus the findings of the study underline the importance of
impaired neutrophil function during sepsis.
blood samples taken from patients on the first day of hospitalization, the
assay identified sepsis patients with very high accuracy" says Jarone Lee,
MD, medical director of the Blake 12 Intensive Care Unit at MGH and a co-author
of the report. "We believe that this
approach may allow us to identify patients at risk of developing sepsis earlier
than any current method
- Additional studies using the
microfluidic device in a larger group and including a more diverse group
of patients are now ongoing at the MGH
conclusion, the discovery of this microfluidic device with the ability to
correctly diagnose/predict sepsis early could be a potential game changer in
the management of acutely ill patients with improved patient prognosis and a
significant reduction in mortality rates.
About Sepsis In Brief
is defined as life-threatening organ dysfunction due to an impaired host
response to infection, and is still a leading cause of death in acutely ill
patients. It is currently diagnosed
based on clinical parameters
(which may be subjective), rather than biologic and/or molecular
have long been known to play a major role in sepsis and studies such as these
that enable precise measurement of neutrophil function can greatly improve the
diagnostic accuracy of as well as treatment (and prevention) of sepsis.
- Ellett F, Jorgensen J, Marand A L, Liu Y M, Martinez M M, Sein V, Butler K L, Lee J & Irimia D. Diagnosis of sepsis from a drop of blood by measurement of spontaneous neutrophil motility in a microfluidic assay. Nature Biomedical Engineering (2018) doi:10.1038/s41551-018-0208-z