Rapid Point of Care Analyzer for the Measurement of Cyanide in Blood

Abstract

A simple, sensitive optical analyzer for the rapid determination of cyanide in blood in point of care applications is described. HCN is liberated by the addition of 20% H3PO4 and is absorbed by a paper filter impregnated with borate-buffered (pH 9.0) hydroxoaquocobinamide Hereinafter called cobinamide). Cobinamide on the filter changes color from orange (λmax = 510 nm) to violet (λmax = 583 nm) upon reaction with cyanide. This color change is monitored in the transmission mode by a light emitting diode (LED) with a 583 nm emission maximum and a photodiode detector. The observed rate of color change increases 10x when the cobinamide solution for filter impregnation is prepared in borate-buffer rather than in water. The use of a second LED emitting at 653 nm and alternate pulsing of the LEDs improve the limit of detection by 4x to ~ 0.5 μM for a 1 mL blood sample. Blood cyanide levels of imminent concern (≥ 10 μM) can be accurately measured in ~ 2 min. The response is proportional to the mass of cyanide in the sample – smaller sample volumes can be successfully used with proportionate change in the concentration LODs. Bubbling air through the blood-acid mixture was found effective for mixing of the acid with the sample and the liberation of HCN. A small amount of ethanol added to the top of the blood was found to be the most effective means to prevent frothing during aeration. The relative standard deviation (RSD) for repetitive determination of blood samples containing 9 μM CN was 1.09% (n=5). The technique was compared blind with a standard microdiffusion-spectrophotometric method used for the determination of cyanide in rabbit blood. The results showed good correlation (slope 1.05, r2 0.9257); independent calibration standards were used.

A fiber optic sensor with a metal organic framework as a sensing material for trace levels of water in industrial gases

“…In this case, light emitting diodes (LEDs) and a photodiode (PD) were used to observe the developed colors, and M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 5 atmospheric NO 2 and O 3 were detected within 5 min [12]. A fiber optic gas sensor with calix [4]arene derivatives has been used to detect reversibly parts-per-million by volume (ppmv) levels of NO 2 [13], and a sensor with cobinamide has been used to detect cyanide in blood after pervaporation by the colored vitamin B12 [14]. These studies support applicability of MOFs that show chromism as fiber optic gas sensors.…”

Development of a cobinamide-based end-of-service-life indicator for detection of hydrogen cyanide gas

“…Complexing of CN(H 2 O)Cbi with CN − can be detected at concentrations as low as 0.25 nM cyanide in solution [20,22]. Using a 583 nm LED, a cobinamide-saturated qualitative filter paper and a photodiode detector, 13.5 ppb HCN released from 1 mL of acidified blood has been detected [23]. In addition to vitamin B12 derivatives, triphenylamine-based chemodosimeters have reported naked-eye detection as low as 1.8 ppm [24].…”

Ultra-sensitive determination of cyanide in surface water by gas chromatography–tandem mass spectrometry after derivatization with 2-(dimethylamino)ethanethiol

“…Spectrophotometry has been widely employed in the determination of cyanide through the use of many types of dye [15][16][17][18][19]. Electrochemical methods using sensors have been routinely used for cyanide analysis [20][21][22].…”