Current Status of the Development of Blood-Based …
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show different dielectric, magnetic, stiffness, and optical properties [43]. Separation of infected RBCs can help in diagnosing diseases. Several physiological tests
are performed on RBCs to track hemoglobin, hematocrit, and malaria detection.
Several researchers have also proposed point-of-care devices for detection of these
parameters. Following paragraphs will give a brief review of these tests based on
point-of-care methods.
There exist various laboratory-based methods to measure hemoglobin, namely, the
cyanmethemoglobin method, Sodium Lauryl Sulfate method [44], Sahli’s method,
Azide-methemoglobin method, Copper-sulfate method, oxyhemoglobin method,
and WHO HCS method [45]. The cyanmethemoglobin method for measuring
hemoglobin is the internationally recommended method. In this method, hemoglobin
is converted to cyanmethemoglobin (hemiglobincyanide, HiCN) using potassium
cyanide. The absorbance of the solution follows the Beer–Lambert’s law [39]. The
absorbance of the solution is compared with the standard HiCN solution of known
concentration at a wavelength of 540 nm in a spectrophotometer to obtain the
hemoglobin concentration [40]. Hemoglobin is also measured using the automated
hematology analyzers and point-of-care handheld devices.
Recently, Yang et al. [46] reported a paper-based hemoglobin measuring test
for resource-limited settings. Hemoglobin measurement was performed by mixing
blood with Drabkin reagent (20 μL droplet) and depositing onto the patterned chromatography paper at the center. The bloodstain was detected by the algorithm and
extracted the color information. The mean color intensity was used to measure
the hemoglobin. Taparia et al. [47] reported a microfluidic approach for measuring
hemoglobin concentration in whole blood. Their device consists of simple optics:
a CMOS sensor and lens. Image analysis was performed to determine the optical
density for measuring hemoglobin using generalized Steinke and Shephard model.
A few studies have also reported hemoglobin measurement using blood analysis
on a cell phone platform [48, 49]. The smartphone methods utilize hemolysis and
spectrophotometric principles to measure absorbance and hemoglobin concentration.
Various point-of-care devices exist for hemoglobin measurement in the market
today. The Hemocue hemoglobinometer and Dia spect are the popular ones [50].
The Hemocue is a portable hemoglobinometer based on the photometric principle,
it consists of a battery-operated spectrometer. The analyzer uses specially designed
microcuvettes containing dried reagents and serves as pipette and a reaction vessel.
Sample blood (10 μL) is introduced by the microcuvette into the instrument by capillary action; the dried reagents in the microcuvette convert the hemoglobin to azidemethaemoglobin. Two wavelengths are used (570 and 880 nm); the color intensity of
the solution is compared against the pre-calibrated standard, and results are generated
within 1 min [45]. Another potential POCT device is the CO-oxiometer, which is
essentially a spectrophotometer incorporated in the gas analyzers. Yet another potent
hemoglobin testing device is the WHO hemoglobin color scale (HCS). It is a lowcost hemoglobin measuring platform for developing world, and for those who have
limited or no access to the laboratory facility. The principle behind this test is the fact
that blood color is dependent on the amount of hemoglobin present in blood. Herein,
a blood drop gets absorbed on a paper and the color is compared with a chart having
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