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Complete Blood Count test has always been requested by physicians to monitor information about the general health status of a patient and for screening different diseases. The test is performed by measuring the number of different cells within the blood (1). In a simple counting of blood cells, the number of red and white blood cells, the number of platelets, concentration of glucose, average volume of red blood cells, average mass and volume of hemoglobin are measured (2). An increase or decrease in either one or more of these components can incorporate or cause a disorder.
Although the test is comprehensive, the procedure of taking a sample to reveal the results takes considerable time, which makes it unsuitable for urgent cases. In addition, it is solely restricted to the labs and hospitals. Therefore, the idea of the Transdermal Patchlab Blood Analyser system was generated to represent the characteristics similar to the CBC test, but in a less invasive and less expensive manner, and in a considerably shorter period of time. The instrument sticks to a certain area of the body such as the forearm, and the transdermal microneedle tips of the patchlab sample the blood from capillaries of the dermis in the patient, and transfer them to other part of the system for further processing.
2. The Transdermal Patchlab Blood Analyser System
"Electronic devices have now reached a stage of dimensions comparable to those of biological macromolecules. This raises exciting possibilities for combining microelectronics and biotechnology to develop new technologies with unprecedented power and versatility." (3)
The primary design of this novel bioMEMS device consists of different compartments. The highlighted segments are comprised of a series of microneedles for sampling the blood; the diluting and clotting preventive section; the "microsieve" micro fluidic filter for separation and distinguishing different particles; a complex detector and readout processing unit; and a transceiver section for monitoring the results.
In the diluting and clotting preventive section, the blood blends with water and heparin to make it more diluted. For each individual sample the concentration of water is important in order to calculate the dilution factor. Since the volume ratio of blood and water is known, the net result would be unaffected; this helps to minimise the possibility of the clotting of the blood.
The factor is crucial in determining the final results of blood tests.
To achieve accurate throughput of the system with a diluted sample the following factors should be considered:
The exact concentration of dilution liquid in each sample
The inert effect of other features of the device on the processing sample
The ability of the system to analyse the sample in the low range (4)
The project is aimed to reach to the point where it enables the Patchlab Blood Analyser device to test a number of people in a short time, and provide usage at any time for the person who is not medically skilled; this will enhance the health care delivery system by eliminating the need of visiting physicians in situations where it is impossible for them.
3. Literature Review
3.1. Skin structure
The outer layer of the skin, the epidermis, consists of five layers which vary in thickness from one to multiple cells (5). These layers provide thickness of 0.1 mm to 1 mm according the area of the body (6). There is completely lack of blood vessel in the epidermis and as a result absence of capillaries network.
The layer beneath the epidermis which contains the capillaries network and nerve endings is called the dermis. Its thickness varies from 0.3 mm to 3 mm in the epidermis (6).
3.2. Capillary and venous blood sampling
In the circulation system, capillaries are the narrowest form of blood vessels with a diameter of between 5 Âµm to 10 Âµm (7). The measurement of a capillary is an alternative to the conventional measurement of blood from the venous. This method constitutes a less invasive and an easier procedure for blood analysis. Capillary and venous blood differences are compared in several studies. Majority of these studies have revealed / concluded that in the while-fasting condition, the concentration of the blood's sample compositions do not vary in the capillary and venous blood samples (8).
However, some studies showed that in the non-fasting condition, the glucose concentration in the capillary blood samples is slightly higher than in the venous blood samples (9).
3.3. Microsieve Filtration
Biocompatible Microsieve Separators are used to separate blood cells and components from one another. The porous structure of the microsieve leads to the capturing of blood cells and glucose, which are diverse in size (10). The following table represents the average size and the number of blood cells per microlitre:
Average number of cell per microlitre of blood
Erythrocytes (Red blood cells)s
7 to 8 Âµm diameter, 2 Âµm height, Donut shape
4.5 x 106 - 5.5 x 106
Leukocytes (White blood cells)
6-8 Âµm diameter
10-15 Âµm diameter
10-12 Âµm diameter
10-12 Âµm diameter
12-15 Âµm diameter
8.5 nm diameter
2.5 x 105 - 3 x 105
Table1. Blood cells and components average size and number (6), (9), (10)
In constructing the microsieve membrane, biocompatibility and surface smoothness are two important characteristics that are considered. In order to eliminate the risk of cell adhesion to the surface or the splitting of the cell membrane, the material must be compatible with the blood. In this case siliconnitride is a considered the appropriate material used to provide complete smooth surface (9).
3.4. Blood Glucose
Glucose (C6H12O6) concentration in the blood is a critical factor since it corresponds to many conventional diseases such as diabetes. Therefore, it has great importance in the current project. The device would be capable to detect the deviation of glucose in the blood. The average level of glucose in the blood is 5 mmol/l while the concentration of it in the blood circulation system is 3.3 to 7 g (11). The largest glucose molecule is 8.6 nm by 8.4 nm (10).
Figure 1. D-Glucose chemical structure (12)
In addition to capturing glucose with microsieves, there is the possibility of introducing the glucose biosensor to the system. The principle of the glucose biosensor is to apply the electric potential difference.
It is possible to classify patchlab micro-needles as an automatic lancing device that should provide sufficient blood by causing the least possible pain. Micro-needles are manufactured by the Microfabrication Method (103) and since microneedles have direct interaction with the human body it is important to examine these elements after production and before applying to the patient. These results to select the most proper microneedles based on their design and material. Therefore, microneedles should undergo various tests such as the clinical test to investigate the level of compatibility, inflammation and pain; and a mechanical test to check the stability as well as the propensity to break in response to stresses (13).
Another challenge is the risk of breakage of the microneedles in the skin due to axial and shears stresses. The latest technology developed to counter this problem is the biodegradable polymer microneedle, which is believed to cause no problem in the afore-mentioned conditions. In addition, the production of this polymer is relatively cheaper than silicon, which is a goodcriterion when dealing with production of high number of the device (13).
Figure 2.Typical type of microneedles (13)
5. Viscosity and Capillary Action
Blood can flow freely because of its low viscosity (it is three to four times more viscous than water) where this can be affected by the presence of high fat and cholesterol in the blood. The flow of blood through microneedles can be modeled by using Poiseuille's equation (14):
Poiseuille's equation: volume rate of flow is (P1-P2) / 8ÆžL
For blood Æž= Pa s (14)
There is no need of a pumping system to cause the blood to flow through the microneedles because the low viscosity and high adhesive attraction of the blood permits it to move easily through the microneedles. In addition, the flow is always laminar and "an approximation to the velocity profile for blood can be obtained by means of the equation of motion and Newton's constitutive equation" (15).
6. Future Objective Outline
In the near future the research will continue on the biodegradable polymer material, the enhancement of the microneedles design, the microsieves structure, a greater in-depth / a more profound study on the glucose biosensor and the simplifying the model where the glucose is the only working molecule.