A Low Blood Volume Platform for Recurrent Anticoagulation and Kidney Monitoring during Continuous Renal Replacement Therapy in Critically Ill Children - ABSTRACT
A Low Blood Volume Platform for Recurrent Anticoagulation and Kidney Monitoring during Continuous Renal
Replacement Therapy in Critically Ill Children
(Fast-Track SBIR PA-20-260)
Acute kidney injury (AKI) is characterized by a sudden decrease in the ability of the kidneys to adequately
maintain electrolyte, acid-base, and fluid balance. Up to 30% of children admitted to intensive care units develop
AKI and the presence of AKI is independently associated with increased length of hospitalization and higher
rates of mortality. Continuous renal replacement therapy (CRRT) has emerged as the preferred dialysis modality
for critically ill children and is becoming increasingly common for newborns and small children (under 10 kg) with
AKI and congenital kidney failure. Frequent monitoring (2-6 times a day) of anticoagulant therapy (heparin,
heparinoids, etc.), kidney function (urea), and electrolyte composition (potassium, phosphorus, etc.) is necessary
during the course of CRRT. Existing laboratory tests require large blood volumes, and the cumulative blood loss
from routine bloodwork contributes to iatrogenic anemia. The majority of critically ill newborns (90% of extremely
low birth weight infants and 58% of premature infants) will require red blood cell transfusions during their time in
the neonatal intensive care unit (NICU) as a result of frequent blood draws.
To meet the critical unmet need for rapid, low volume blood tests for CRRT monitoring in newborns and children,
we will develop a panel of four assays on our near-patient digital microfluidic (DMF) platform to provide
comprehensive profiling of anticoagulation dosing, kidney function, and phosphorus balance. Our innovative
system will simultaneously measure anti-factor Xa (anti-FXa), activated partial thromboplastin time (aPTT), blood
urea nitrogen (BUN), and phosphorus from < 50 µL of whole blood input. Plasma separation from whole blood
(necessary for all four assays) will be automated on the cartridge to facilitate testing near the patient. By
combining four technically complex assays (typically sent to different sections in a lab such as hematology and
chemistry) into a single automated test, we can reduce sample-to-answer time and personnel time needed to
perform each individual assay, and can significantly reduce the cumulative volume of blood required for recurrent
monitoring over the full course of CRRT therapy.
Our collaborators on this Fast-Track project include pioneers in pediatric acute care nephrology with multiple
recent publications describing novel approaches to CRRT in newborns. Phase I of the project will establish
feasibility of the proposed testing platform through development of DMF anti-FXa, aPTT, BUN, and phosphorus
assays and demonstration of sufficient analytical and clinical performance. Phase II will combine the four assays
into a multiplexed reaction with a time-to-result of under 15 minutes, evaluate the analytical performance and
clinical concordance of each assay, and conduct onsite lead user testing of the system to establish reliability and
usability. Our final product will initially be marketed for use in newborn and pediatric patients undergoing CRRT.
Secondary markets will include both pediatric and adult patients undergoing cardiac surgery or other procedures
associated with kidney failure, toxin removal, and ultrafiltration of fluid.
