

Component	Source	Catalog Number

Mosfet Drivers	International Rectifier	IRLD024
	El Segundo, CA
Op-Amp	National Semiconductor	LM358
	Santa Clara, CA
Status LED	Hewlett-Packard	HLMPD150
	Newark Electronics
	Schaumburg, IL
Pressure Sensor	Sensym, Inc.	SDX15D4
	Milpitas, CA

FIG. 3 illustrates by way of a block diagram how the foregoing electronic components can be arranged to carry out the method of the present invention.[0051]

Operation of the blood extraction device[0052]10 will now be described. Referring now to FIGS. 1, 2 and3, thenosepiece30 of the lancingassembly16 is applied to the surface of the skin, designated herein by the letter “S”. The end of thenosepiece30 that contacts the skin is equipped with aseal32. The purpose of theseal32 is to prevent air from leaking intoblood extraction chamber34, so that thevacuum pump14 can provide sufficient suction action for increasing the availability of blood to the area of the skin from which the sample is to be extracted, stretching the skin, and extracting the sample of blood from the unobstructed opening in the skin. Theseal32 surrounds anopening33 in thenosepiece30. Theopening33 in the nosepiece allows communication between the surface of the skin and ablood extraction chamber34 in thenosepiece30. Theseal32 is preferably made of a rubber or an elastomeric material. FIG. 4 illustrates an alternative position for theseal32. In FIG. 4, the seal is designated by thereference numeral32′. The remaining parts of FIG. 4 are the same as those of FIG. 2, and , accordingly, retain the same reference numerals as were used in FIG. 2.

The[0053]

switch

22 is actuated, typically by being pressed, thereby activating theelectronics20, which starts thevacuum pump14. Thevacuum pump14 then provides a suction action. The suction action of thevacuum pump14 causes the skin circumscribed by theseal32 to become engorged with blood. Engorgement of the skin with blood is accompanied by a stretching of and rising up of the skin up toopening33.

After an appropriate period of time, which is typically pre-set by the programmer of the electronics, the lancing[0054]

assembly

16 is triggered, thereby causing thelancet36 to penetrate the skin that has risen up to theopening33 and that is engorged with blood. Thelancet36 is preferably triggered automatically, by asolenoid valve38 that causes a vacuum-actuated piston (not shown) to trigger thelancet36. Thelancet36 is then retracted, preferably automatically. Thereupon, the blood flows out of the unobstructed opening resulting from thelancet36, and, aided by the vacuum generated by thevacuum pump14, is collected. When sufficient blood has been collected or a pre-set time interval has passed, theelectronics20 causes thevacuum pump14 to stop. The device10 can then be removed from the surface of the skin after another solenoid valve (not shown because it is hidden under solenoid valve38) is opened to vent the vacuum to allow ease of removal of the device from the surface of the skin. Solenoid valves suitable for use with the apparatus described herein are commercially available from The Lee Company, Essex, Conn. and have the part number LHDA0511111H.

The blood is preferably directly collected on the application zone of a glucose detector, e.g., a reflectance strip or biosensor. The blood can then be used as the sample for a determination of glucose concentration in blood. Alternatively, the blood can be collected by other collection devices, such as, for example, a capillary tube or absorbent paper.[0055]

The apparatus of the present invention can include a glucose detector for analyzing the blood sample extracted by the apparatus. Glucose detectors are well-known in the art. With respect to glucose monitoring, there are two major categories of glucose detectors—reflectometers and biosensors. Representative examples of reflectometers suitable for this invention are described in U.S. Pat. No. 4,627,445, incorporated herein by reference. Representative examples of biosensors suitable for this invention are described in U.S. Pat. No. 5,509,410, incorporated herein by reference.[0056]

The glucose detector is preferably disposed in the[0057]

nosepiece

30 of the lancingassembly16. The glucose detector must be located at a position sufficiently close to the site of blood extraction so that the quantity of extracted blood collected will be sufficient to carry out a standard glucose monitoring test. Typically, this distance will preferably be no more than 5 mm from the site of blood extraction, more preferably no more than 3 mm from the site of blood extraction, most preferably no more than 1 mm from the site of blood extraction. Care must be taken in the placement of the glucose detector so that the detector does not adversely affect the vacuum, when a vacuum is employed to aid in the extraction of blood. In addition, theglucose detector40 should be modified, if necessary, so that the blood collected in the collection zone of the glucose detector is capable of being used to activate the glucose detector.

FIG. 2 also illustrates a manner for disposing a[0058]

glucose detector

40 in thenosepiece30 of the lancingassembly16.

This invention provides numerous advantages over blood extraction devices of the prior art. Among these advantages are the following:[0059]

1. Ability to use parts of the body, other than the finger, as a site for the extraction of blood;[0060]

2. Reduction of pain by eliminating the need to lance the finger;[0061]

3. Increase in speed of collection of blood samples by means of pre-treatment comprising a combination of stretching of the skin in conjunction with heat or vacuum or both heat and vacuum;[0062]

4. Incorporation of glucose detector in apparatus for extracting the blood sample.[0063]

The following examples illustrate various features of the present invention but is not intended to in any way limit the scope of the invention as set forth in the claims. In the following examples, the term “pierce” and forms thereof and the term “puncture” and forms thereof are used interchangeably.[0064]

EXAMPLESExample 1

This example illustrates that greater volumes of blood can be extracted and collected by applying a vacuum, pulsed or continuous, after piercing than can be extracted and collected when no vacuum is applied. No vacuum was applied prior to piercing.[0065]

Each of four people had his forearm (dorsal forearm) punctured four times (at four different positions on the forearm) with a “BD ULTRA-FINE” lancet in a “MEDISENSE” lancet assembly (Model no. 97101) at two different levels of vacuum (−2.5 psig and −5.0 psig) and for each different vacuum pulsing frequencies (0, 0.2, 0.8, 3.2, 12.8, 25, 100 hertz). The vacuum was applied with a pipette tip having a diameter of 8 mm (“RAININ RT-200”). Four control runs without a vacuum were also carried out (one puncture per person). A total of 60 punctures per person were carried out. Accordingly, it can be seen that a total of 240 runs were carried out.[0066]

The vacuum was applied for a duration of 30 seconds after puncturing. Blood was collected into capillary tubes. In the control runs, the samples were extracted and collected 30 seconds after puncturing. The amount of blood collected was determined by measuring the length of blood in the tubes. The percentage of collections in which the volume of blood collected exceeded 1.0 μL was calculated. Sensation of pain was also recorded. The following pain scores were used:[0067]

Pain of 1=person did not feel anything or not sure if anything was felt[0068]

Pain of 2=person felt definite prick, not as painful as piercing of finger by standard finger lancet[0069]

Pain of 3=person felt definite pain, approximately equal to a piercing of finger by standard finger lancet[0070]

Blood Collection Results are Set Forth in Table I.

[0071]

TABLE I


	Average	Percent of	Average	Percent of
	volume of	samples	volume of	samples
	blood sample	having >1 μL	blood sample	having >1 μL
	collected at	of blood	collected at	of blood
Frequency	−2.5 psig	collected at	−5.0 psig	collected at
(hertz)	(μL)	−2.5 psig	(μL)	−5.0 psig

0	1.6	69	3.1	94
(Con-
tinuous)
0.2	1.1	44	3.0	94
0.8	1.1	63		75
3.2	1.5	56	3.8	75
12.8	1.8	75	3.1	100
25	2.3	75	3.2	94
100	2.4	81	2.7	88

With no vacuum, average volume of blood collected was 0.8 μL and 31% of the samples collected contained more than 1 μL. The pain results were as follows:[0072]



	pain of 1 = 81%
	pain of 2 = 17%
	pain of 3 = 2%

The control runs (no vacuum) provided much lower volumes of blood collected than did the runs where vacuum was applied. Increased vacuum resulted in higher volumes of blood extracted. The pain was minimal, with only 2% of the punctures resulting in pain comparable to that resulting from a piercing of the finger.[0073]

Example 2

This example illustrates that application of vacuum prior to piercing as well as after piercing results in a greater volume of blood extracted than does the application of vacuum only after piercing.[0074]

Each of four people had his forearm (dorsal forearm, middle of forearm) punctured sixteen times (at sixteen different positions on the forearm) with a “BD ULTRA-FINE” lancet in a modified “MEDISENSE” lancet assembly at four different levels of vacuum. The four levels of vacuum used were −2.5, −5.0, −7.5, and −10.0 psig. The “MEDISENSE” lancet device was modified to allow vacuum to be pulled through the lancet assembly. Four punctures per person were carried out at each of the four levels of continuous vacuum. Accordingly, it can be seen that a total of 64 runs were carried out.[0075]

Prior to puncturing, the vacuum was applied for a period of 30 seconds; subsequent to puncturing, the vacuum was applied for a period of 30 seconds. The skin was under vacuum at the time the lancet was triggered. After the lancet was triggered, the lancet assembly was removed, and the vacuum was used to apply the same level of vacuum that had been used for the vacuum prior to puncturing. The vacuum, both prior to puncturing and subsequent to puncturing, was applied with a pipette tip having a diameter of 8 mm (“RAININ RT-200”). The pipette tip of the vacuum device was held level to the plane of the skin. Blood was then collected into capillary tubes. The amount of blood collected was determined by measuring the length of blood in the tubes. The percentage of collections in which the volume of blood collected exceeded 1.0 μL was calculated. Sensation of pain was also recorded. Blood collection results are set forth in TABLE II.[0076]

TABLE II


		Percent of samples
	Average volume of blood	having >1 μL of blood
Vacuum level (psig)	sample collected (μL)	collected

−2.5	4.6	94
−5.0	7.8	100
−7.5	9.2	100
−10.0	14.0	100

The pain results were as follows:[0077]



	pain of 1 = 58%
	pain of 2 = 31%
	pain of 3 = 11%

A nearly linear relationship between level of vacuum and volume of blood collected was observed. The average volume of blood collected with vacuum applied prior and after piercing was approximately twice that collected with vacuum applied only after piercing without vacuum applied prior to piercing. See the results of Example 1 for this comparison (7.8 μL vs. 3.1 μL). The volume of blood collected was always above 1 μL for all levels of vacuum, except −2.5 psig.[0078]

Example 3

This example illustrates that localized heating of the area to be pierced followed by vacuum after piercing results in a greater volume of blood being extracted than does extraction with only vacuum after piercing.[0079]

Each of four people had his forearm (dorsal forearm, middle of forearm) punctured eight times (at eight different positions on the forearm) with a “BD ULTRA-FINE” lancet in a “MEDISENSE” lancet assembly with heat applied (45° C.) prior to piercing for two different time periods, 15 seconds and 60 seconds. A total of 32 runs were carried out, 16 runs where the pre-heating duration was 15 seconds and 16 runs where the pre-heating duration was 60 seconds.[0080]

Heat was applied with a heating block, which was an aluminum block having a square face covered with a “KAPTON” film heater element controlled by an “OMEGA” DP41 temperature controller using a T-type thermocouple. Vacuum was applied after each puncturing for 30 seconds at −5.0 psig. Blood was collected into capillary tubes. The amount of blood collected was determined by measuring the length of blood in the tubes. The percentage of collections in which the volume of blood collected exceeded 1.0 μL was calculated. Pain was also tracked. Blood collection results are set forth in TABLE III.[0081]

TABLE III


		Percent of samples
Pre-piercing heating	Average volume of blood	having >1 μL of blood
duration (seconds)	samples collected (μL)	collected

15	6.91	94
60	11.6	100

The pain results were as follows:[0082]



	pain of 1 = 91%
	pain of 2 = 9%
	pain of 3 = 0%

The average volume of blood collected using a pre-heating duration of 15 seconds was more than twice the average volume of blood collected at a post-puncturing vacuum level of −5.0 psig., with no pre-heating. See the results of Example 1 for this comparison (6.91 μL vs. 3.1 μL). The average volume of blood collected using a pre-heating duration of 60 seconds was approximately four times the average volume of blood collected at a post-puncturing vacuum level of −5.0 psig, with no pre-heating. See the results of Example 1 for this comparison (11.6 μL vs. 3.1 μL).[0083]

Example 4

This example illustrates the effect that stretching the skin upwardly with a vacuum has on the extraction of blood.[0084]

Each of four people had his forearm (dorsal forearm, middle of forearm) punctured eight times (at eight different positions on the forearm) with a “BD ULTRA-FINE” lancet in a “MEDISENSE” lancet assembly. Vacuum was applied for a period of 30 seconds prior to puncturing at −5.0 psig using two different vacuum fixtures. The first fixture was a 15 mm diameter vacuum fixture (i.e., a hollow cylindrical tube) used without a net strung across the opening of the tube. The second fixture was a 15 mm diameter vacuum fixture (i.e., a hollow cylindrical tube) used with a net strung across the opening of the tube. The net prevented skin from being raised up into the vacuum fixture. The same vacuum fixture used prior to puncturing was applied for a period of 30 seconds after puncturing. The fixture was held level with the plane of the skin. Four punctures were carried out per person per condition (without net, with net). Accordingly, it can be seen that a total of 32 runs were carried out. Blood was collected into capillary tubes. The amount of blood collected was determined by measuring the length of blood in the tubes. The percentage of collections in which the volume of blood collected exceeded 1.0 μL was calculated. Sensation of pain was also recorded. Blood collection results are set forth in TABLE IV.[0085]

TABLE IV


		Percent of samples
	Average volume of blood	having >1 μL of blood
Net across nosepiece	sample collected (μL)	collected

No	5.2	87
Yes	0.6	19

The pain results were as follows:[0086]



	pain of 1 = 94%
	pain of 2 = 6%
	pain of 3 = 0%

The magnitude of the difference in volume of blood collected and success rates (i.e., percent of samples having >1 μL of blood collected) between the condition of stretching the skin in combination with a vacuum and the condition of not stretching the skin in combination with a vacuum was unexpected. The pain scores were low. This example demonstrates that the combination of skin stretching and applied vacuum significantly increased the volume of blood extracted.[0087]

Example 5

This example illustrates the effect the area of the extraction site has on the volume of blood collected.[0088]

Each of four people had his forearm (dorsal forearm, middle of forearm) punctured at 32 different positions on the forearm with a “BD ULTRA-FINE” lancet in a modified “MEDISENSE” lancet assembly. The “MEDISENSE” lancet assembly had been modified with a more powerful spring and a port had been added.[0089]

Vacuum was applied for less than five seconds prior to puncturing. The forearm was punctured under a vacuum of either −5.0 psig or −7.5 psig. The vacuum applied was maintained for 30 seconds after puncturing. The diameter of the pipette tip used to apply vacuum after puncturing was varied, with diameters of 4, 6, 8, and 10 mm being used. Four punctures per condition (diameter, vacuum level) were carried out per person. Accordingly, it can be seen that a total of 128 runs were carried out. Blood was collected into capillary tubes. The amount of blood collected was determined by measuring the length of blood in the tubes. The percentage of collections in which the volume of blood collected exceeded 1.0 μL was calculated. Sensation of pain was also recorded. Blood collection results are set forth in TABLE VA and VB.[0090]

TABLE VA


vacuum level = −5.0 psig

		Percent of samples
Vacuum diameter	Average volume of blood	having >1 μL of blood
(mm)	sample collected (μL)	collected

4	0.3	0
6	1.7	69
8	3.4	94
10	4.1	100

[0091]

TABLE VB


vacuum level = −7.5 psig

		Percent of samples
	Average volume of blood	having > 1 μL of
Vacuum diameter (mm)	sample collected (μL)	blood collected

4	0.8	25
6	3.1	94
8	3.4	81
10	6.3	94

The pain results were as follows:[0092]



	pain of 1 = 89%
	pain of 2 = 10%
	pain of 3 = 1%

The volume of blood collected and success rates (i.e., percent of samples having >1 μL of blood collected) were found to vary directly with the area of skin raised up into the device by the vacuum. A much greater volume of skin was raised up into the larger diameter pipette tip than into the smaller diameter pipette tips.[0093]

Example 6

This example illustrates that a plastic multiple point lancet can be used with heat and vacuum to collect a useful amount of blood.[0094]

Each of four people had his forearm (dorsal forearm, middle of forearm) punctured sixteen times (at sixteen different positions on the forearm) with a Greer Derma PIK® System for allergy testing (Greer Laboratories, Inc., Lenoir, N.C. 28645) modified to fit into a “MEDISENSE” lancet assembly. Pre-heating was carried out at approximately 40° C. and 45° C. for 15 and 60 seconds prior to puncturing. Four punctures were carried out per condition (temperature, time) per person. Accordingly, it can be seen that a total of 64 runs were carried out.[0095]

Heat was applied with a heating block, which comprised an aluminum block having one face covered with a “KAPTON” film heater element controlled by an “OMEGA” DP41 temperature controller using a T-type thermocouple and the opposite face in contact with the larger base of a frustum of a cone made of copper. The larger base of the frustum had a diameter of 0.50 in. The height of the frustum was 0.50 in. The smaller base of the frustum had a diameter of 0.35 in. The smaller base had a cylindrical opening having a diameter of 0.125 in. The cylindrical opening had a common axis with the frustum. The cylindrical opening reduced the heating surface of the copper frustum. Vacuum (−5.0 psig) was applied for a period of 30 seconds after puncturing. The vacuum in contact with the skin was formed by a pipette tip having a diameter of 8 mm. The pipette tip was held level with the plane of the skin. Blood was collected into capillary tubes. The amount of blood collected was determined by measuring the length of blood in the tubes. The percentage of collections in which the volume of blood collected exceeded 1.0 μL was calculated. Sensation of pain was also recorded. Blood collection results are set forth in TABLE VI.[0096]

TABLE VI


	Average volume of	Percent of samples
Temperature (° C.)/	blood	having > 1 (μL) of
Time (seconds)	sample collected (μL)	blood collected

40/15	2.4	31
40/60	2.6	50
45/15	2.3	56
45/60	5.2	81

The pain results were as follows:[0097]



	pain of 1 = 100%
	pain of 2 = 0%
	pain of 3 = 0%

This example demonstrates that a blood extraction process employing a multi-point plastic lancet, pre-piercing heating, skin stretching, and post-piercing vacuum can extract at least 1 μL of blood at least 50% of the time.[0098]

Various modifications and alterations of this invention will become apparent to those skilled in the art without departing from the scope and spirit of this invention, and it should be understood that this invention is not to be unduly limited to the illustrative embodiments set forth herein.[0099]