Novel Assay for Ethylene Glycol Toxicity

Period of Performance: 07/01/2002 - 05/31/2003

$413K

Phase 2 SBIR

Recipient Firm

Micronix, Inc.
Carmel, IN 46032
Principal Investigator

Abstract

DESCRIPTION: (Applicant's abstract) Poisoning from ethylene glycol is a potentially lethal medical emergency but can be treated effectively when recognized early. Conversely, when diagnosis is late, the outcome is usually poor. The major pathogenic factor is metabolic acidosis from glycolic acid (glycolate). Because laboratory testing for ethylene glycol and glycolate is severely restricted, timely diagnosis depends on comparatively nonspecific physical signs and laboratory tests. Lack of access to specific testing and need for differentiation from conditions featuring similar symptoms constitute a unique medical dilemma. Recognizing these deficiencies we propose to develop novel, specific enzymic assays for ethylene glycol and glycolate. Two product configurations are perceived: 1) aqueous reagents for existing clinical analyzers (serum, quantitative); 2) a dry-chemistry, dual-analyte point-of-care testrip method (whole blood, semi-quantitative).The POC method is a dual-analyte test tab device for the simultaneous estimation of ethylene glycol and glycolate from approximately two (2) microliters of whole blood without centrifugation or any other form of sample or reagent handling. To make such a level of miniaturization and simplicity feasible, we have developed a capillary fill sampling technique permitting specimen dosing, plasma separation, and red cell removal in one wholly integrated step. Because of rapid metabolism of (flontoxic) ethylene glycol and the longer half life of (toxic) glycolate, the latter provides better prognostic information and improved clinical sensitivity, especially late post-ingestion. Thus, rapid and simultaneous availability of test results for both analytes expands the window of diagnostic/therapeutic opportunity. Socioeconomic benefits are: 1) reducing expensive gas chromatographic screening, confirmatory and other testing; 2) averting late or unnecessary treatment; 3) cutting intensive care and hospital stay; 4) abating long term morbidity (renal dialysis). PROPOSED COMMERCIAL APPLICATION: Most current gas chromatographic screening and confirmatory methods for ethylene glycol require derivatization, sample pretreatment and special columns. Direct methods are fraught with analytical problems such as peak overlap and trailing. Cases have been reported where other compounds were identified as ethylene glycol with serious consequences. All methods require specialized equipment unavailable in most laboratories, are technically demanding, time consuming, and relatively insensitive. For these reasons access to timely and reliable testing for ethylene glycol is extremely limited. Testing for the clinically more sensitive and relevant toxic metabolite glycolic acid is essentially non-existant. Not a single routine clinical analyzer currently exists offering either an ethylene glycol or glycolate method. The proposed products would solve these problems.