# RAPID ELECTROCHEMICAL BIOSENSOR FOR POINT-OF-CARE DIAGNOSIS OF JOINT INFECTION

> **NIH NIH R44** · CLEU DIAGNOSTICS, LLC · 2022 · $1,000,000

## Abstract

Periprosthetic joint infection (PJI) is a devastating complication following total joint replacement (TJR) often with
major long-term consequences and morbidity. As many as 100,000 orthopedic infections are diagnosed each
year in the US, a number that is expected to rise exponentially. However, the scope of the problem is much
larger. Persistent pain is reported in up to 80% of patients after joint surgery, and all painful orthopedic implants
require a complete evaluation to rule out the possibility of PJI. Concern for infection is also the single most
common reason for patients to present to the emergency department after TJR. Unfortunately, making the
diagnosis of infection remains a major challenge, especially since outward clinical signs, such as erythema and
swelling, are not specific to PJI. Immediate and accurate diagnoses that also avoid unnecessary overtreatment
are critical for favorable outcomes, especially given that PJI management often requires multiple operations and
prolonged hospitalization. Nevertheless, underlying infections still commonly go undetected due the nature of
existing diagnostics, which are outdated, slow, and imprecise. Problems include the inability to isolate infectious
organism(s) in 20-50% of cases (‘culture-negative’), long incubation times required to isolate certain pathogens,
and the relatively high incidence of false positives. Alternative diagnostic tools are also limited – either synovial
fluid must be transported to a central laboratory for testing or outdated point-of-care (POC) diagnostic technology
must still be employed that yields less accurate, binary results (‘infected’ or not). So how should physicians make
timely and accurate diagnoses? Our team was the first to discover the diagnostic value of synovial fluid leukocyte
esterase (LE), an antimicrobial protease released by activated neutrophils recruited to sites of bacterial infection.
Since that discovery, the original LE ‘dipstick’ test (Roche Chemstrip®) has been used by physician to aid in PJI
diagnosis with a high diagnostic accuracy of about 89% and a negative predictive value as high as 97%.
Nevertheless, the test in its original form designed for urinalysis is impractical for widespread use in orthopedics.
The ‘dipstick’ is a dry chemical reagent pad, in which a surface reagent reacts with esterase in the sample to
produce a purple dye. The result is read by a clinician based on the degree of color change on the test pad.
Unfortunately, lack of objectivity severely limits its clinical reliability. Joint fluid samples must also be centrifuged
in an attempt to remove blood and debris that can distort results. Our breakthrough LE test is a POC diagnostic
assay that provides a rapid quantitative LE measurement with just a tiny droplet of synovial fluid. Results are
immediately available to providers via a mobile app in just 2 minutes to drive clinical decisions. In Phase I, we
overcame significant challenges and delivered a highly stable pro...

## Key facts

- **NIH application ID:** 10481724
- **Project number:** 2R44AI142886-02A1
- **Recipient organization:** CLEU DIAGNOSTICS, LLC
- **Principal Investigator:** Andrew Neil Fleischman
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,000,000
- **Award type:** 2
- **Project period:** 2019-04-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10481724

## Citation

> US National Institutes of Health, RePORTER application 10481724, RAPID ELECTROCHEMICAL BIOSENSOR FOR POINT-OF-CARE DIAGNOSIS OF JOINT INFECTION (2R44AI142886-02A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10481724. Licensed CC0.

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