WO2010109461A1

WO2010109461A1 - A painlessly hand-held apparatus useful for piercing, detection and quantization of an analyte and methods thereof

Info

Publication number: WO2010109461A1
Application number: PCT/IL2010/000244
Authority: WO
Inventors: Ilan Greenberg
Original assignee: Sindolor Medical Ltd.
Priority date: 2009-03-23
Filing date: 2010-03-23
Publication date: 2010-09-30

Abstract

The present invention provides a hand-held apparatus adapted to pierce a region of a patient's skin, to detect and to quantize an analyte in the blood or interstitial fluid; wherein said apparatus comprising:a. piercing mechanism adapted to pierce said patient's skin, to detect and to quantize said analyte;b. at least one displaying unit in communication with said piercing mechanism for displaying said analyte quantity to said patient; and, c. a cooling mechanism adapted to eliminate the pain caused by said piercing to said patient; further wherein said patient reported pain during said piercing is less than 2 on the SVAS scale.

Description

A PAINLESSLY HAND-HELD APPARATUS USEFUL FOR PIERCING, DETECTION AND QUANTIZATION OF AN ANALYTE AND METHODS

THEREOF

FIELD OF THE INVENTION

The present invention pertains to a glucose meter, and more specifically, to a glucose meter incorporated with a strip needle adapted to eliminate or al east alleviating the pain caused by piercing the patient's skin.

BACKGROUND OF THE INVENTION

Diabetes mellitus, often simply diabetes, is a syndrome characterized by disordered metabolism and inappropriately high blood sugar (hyperglycemia) resulting from either low levels of the hormone insulin or from abnormal resistance to insulin's effects coupled with inadequate levels of insulin secretion to compensate. The characteristic symptoms are excessive urine production (polyuria), excessive thirst and increased fluid intake (polydipsia), and blurred vision; these symptoms may be absent if the blood sugar is mildly elevated. Diabetes mellitus is currently a chronic disease, without a cure, and medical emphasis must necessarily be on managing/avoiding possible short-term as well as long-term diabetes- related problems. There is an exceptionally important role for patient education, dietetic support, sensible exercise, self glucose monitoring, with the goal of keeping both short-term blood glucose levels, and long term levels as well, within acceptable bounds. A glucose meter (or glucometer) is a medical device for determining the approximate concentration of glucose in the blood. It is a key element of home blood glucose monitoring by people with diabetes mellitus or with proneness to hypoglycemia.

A procedure of the glucose blood test may be nominally divided to two steps: (i) blood sampling and (ii) carrying out of an analysis.

Usually the blood sampling step is realized by two different manners. In accordance with first one, an opening is created on patient's body, preferably on a hand finger. An originated drop of blood is transferred to an analyzer. The second variant of blood sampling comprises skin perforation and following sucking blood into an analyzer by means of creating reduced pressure inside the analyzer or cohesion forces.

Two main methods of glucose blood analysis are used in commercially available glucose meters: (i) electrochemical reaction and (ii) optical absorption. An electrochemical sensor is designed to determine the amount and concentration of an analyte in a sample having a volume of less than about 1 μL. The sensor has a working electrode coated with a non-leachable redox mediator. The redox mediator acts as an electron transfer agent between the analyte and the electrode. In addition, a second electron transfer agent, such as an enzyme, can be added to facilitate the electrooxidation or electroreduction of the analyte. The redox mediator is typically a redox compound bound to a polymer. The preferred redox mediators are air-oxidizable. The amount of analyte can be determined by coulometry. One particular coulometric technique includes the measurement of the current between the working electrode and a counter or reference electrode at two or more times. The charge passed by this current to or from the analyte is correlated with the amount of analyte in the sample. Other electrochemical detection methods, such as amperometric, voltammetric, and potentiometric techniques, can also be used.

An optical absorption is realized by means of a reagent test strip adapted for use in a blood glucose meter. A sample of blood is applied to one surface of a matrix on the strip and the meter measures the reflectance of the opposite surface of the matrix at about 635 nm and 700 nm and calculates from the reflectance the concentration of glucose in the sample. The portion of the applied sample that penetrates the matrix and is visible from the testing surface does not absorb to any appreciable extent at 700 nm. Nevertheless, the glucose-containing sample interacts with the components of the reagent-containing matrix to cause a change in reflectance at 700 nm that simulates the effect of the blood color.

US patent application 2002/0177788 ('788) discloses a method and device for combining the sampling and analyzing of sub-dermal fluid samples, e.g., interstitial fluid or whole blood, in a device suitable for hospital bedside and home use. It is applicable to any analyte that exists in a usefully representative concentration in the fluid, and is especially suited to the monitoring of glucose. The device taught by '788, comprises a penetration probe having a penetrating end insertable into the dermal layer and comprises a chamber of an electrochemical sensor connected to a controller. The aforesaid penetration probe functions as a lancet and a sensor concurrently.

Japanese patent 09094231 ('23I) discloses a similar arrangement. A needle insertable into the dermal layer comprises an electrochemical sensor enabling detecting an analyte, preferably glucose. In accordance with '231, a subjective substance in the blood is unsteadily and electrically measured and the output is informed as a voicing result through a device responding by sound, thus the device is readily used for self-care administration by a blind man or the aged.

However, it should be taken into account that performing blood tests causes cutaneous pain due to injury to the skin or superficial tissues. Insertion of a needle into the skin is known to be accompanied by a localized sensation of pain. Accordingly, it would be an advantage to desensitize skin into which a needle is being introduced.

There are patents and patents applications relating to pain relieve. An example of such teaching is to be found in US patent application 2005/005626 ('626) which discloses a cooling device for application to the patient's skin in order to relieve pain during a medical procedure. The device has an annular cooling contact element for application to the skin and a cooling means is disposed laterally of the contact element, to one side thereof. A heat flow path extends laterally from the contact element, transversely of the axis of the contact element, to the cooling means, so that in use heat is withdrawn from the contact element to the cooling means. A temperature detector is disposed to detect temperature within the envelope of the annular cooling contact element. Although application '626 does describe the used of Peltier Cooled Cold Plate in order to cool the skin, it does not describe a device which is able to provide a medical procedure combined with pain relieving elements. Thus, there is a long felt need for a device that combines both the act of sampling the blood and carrying out of an analysis while eliminating (or at least alleviating) the pain. It is a well known fact that cooling the skin prior to piercing desensitizes the skin and by that relieves the pain caused to the patient due to the piercing. A well known theory that connects pain and cooling of the skin is the Pain Gate Control Theory. The Pain Gate Control Theory is based on the fact that small diameter nerve fibers carry pain stimuli through a 'gate mechanism' but larger diameter nerve fibers going through the same gate can inhibit the transmission of the smaller nerves carrying the pain signal. Chemicals released as a response to the pain stimuli also influence whether the gate is open or closed for the brain to receive the pain signal. This lead to the theory that the pain signals can be interfered with by stimulating the periphery of the pain site, the appropriate signal-carrying nerves at the spinal cord, or particular corresponding areas in the brain stem or cerebral cortex. Complementary Therapists need to concern themselves with the first two options in order to effectively modify the pain signal. It is generally recognized that the 'Pain gate' can be shut by stimulating nerves responsible for carrying the touch signal (mechanoreceptors) which enables the relief of pain through the application of cooling the area. However, it is still an unanswered question of what will be the cooling rate. The optimal cooling rate is still unknown due to the fact that the psychophysical responses to cooling rate during static contact of the skin with a cooled plate in normal human subjects are not well understood. Some claim that pain indices (such as visual analog scale and McGiIl pain questionnaire) were higher for slower cooling rates (Harrison JL., Davis KD. Pain, 83, 1999, 123). That is due to fact that in slower cooling rates the cooling of the deeper dermal tissue is more pronounced, therefore, according, to the Gate Control Theory the mechanoreceptors are stimulated and the 'Pain gate' is shut. Others claim that faster rates led to cold tissue injuries and therefore to stronger rather than weaker nociceptive sensations (Jay O., Havenith G., J. Appl. Physiol. 100, 2006, 1596).

Reference is now made to Fig. 1 which is a schematic diagram of the relationship between the pain caused to the patient and the cooling rate. The cooling rate refers hereinafter as the ratio between the temperature differences (between the initial tissue's temperature and the final tissue's temperature) to the time difference. It can be seen that both in slow and fast cooling rates a considerable amount of pain is caused to the patient. It can also be seen from the figure that there is a cooling rate in which minimum pain is caused the patient. Patents that disclose cooling means prior to/during and after the piercing can be found in US Patents 5,578,014, 6,290,683, 6,936,028 and 5,921,963. However, those patents don't describe the elimination of pain nor disclose what are the factors that enable a painless piercing of the skin (such as cooling rate, the depth to which the needle penetrates, the final temperature at said depth et cetera). Moreover, those patents do not mention cooling the skin by a Peltier Cooled Cold Plate (PCCP). Furthermore, those patents don't mention applying pressures (as will be discussed later on).

Thus, there is a long felt need for a device that can optimize the cooling rate such that the pain caused to the patients while piercing is minimal.

Another variable that can influence the amount of pain caused is pressure. According to the Gate Control Theory, applying pressure (i.e. rubbing or massaging the area) stimulates the mechanoreceptors and the 'Pain gate' is shut.

Moreover, it is well know in the literature that applying pressure on the skin leads to a reduction in blood flow in the upper layers of the skin. By reducing the blood flow to the area, the cooling of that area is more efficient. Thus, again the mechanoreceptors are stimulated and the 'Pain gate' is shut.

Thus, there is a long felt need for a device that can optimize the amount of pressure applied on the skin such that the pain caused to the patients is minimal. Moreover, in view of the above there is still a long felt need for a device that will provide blood sampling and analyzing of an analyte while eliminating (or at least alleviating) the pain caused to the patient.

SUMMARY OF THE INVENTION

It is one object of the present invention to provide a hand-held apparatus adapted to pierce a region of a patient's skin, to detect and to quantize an analyte in the blood or interstitial fluid; wherein said apparatus comprising: a. piercing mechanism adapted to pierce said patient's skin, to detect and to quantize said analyte; b. at least one displaying unit in communication with said piercing mechanism for displaying said analyte quantity to said patient; and, c. a cooling mechanism adapted to eliminate (or at least alleviating) the pain caused by said piercing to said patient; further wherein said patient reported pain during said piercing is less than 2 on the SVAS scale.

It is another object of the present invention to provide the hand-held apparatus as defined above, wherein said piercing mechanism comprises: i. at least one strip-needle; said strip needle is adapted to pierce a region of said skin, and to penetrate to depth D in said skin; said depth D is characterized by an initial temperature T; said strip-needle comprising (a) an actuator adapted to activate said strip- needle; and, (b) an electrochemical sensor adapted to indicate the amount of said analyte; said displaying unit comprising: i. a display in communication with said electrochemical sensor, and adapted for displaying said analyte amount to said patient; said cooling mechanism, comprising: i. at least one attachable cooling means, especially a Peltier Cooled Cold

Plate (PCCP), in connection with a radiator/thermal mass and sufficient DC power supply; said PCCP is characterized by an effective surface area S; said effective surface S is optimized such that said pain caused by said piercing is eliminated (or at least alleviating); said PCCP is characterized by temperature TJ_PCCP; said PCCP adapted for cooling a portion of said skin prior to and/or during and/or after piercing thereof by said piercing mechanism such that the cooling is obtained at said depth D; said depth D is cooled from said initial temperature T to a final temperature T_D (ΔT) in a period of time t (Δt) by said PCCP; said final temperature TD of said depth D is higher than about 0 and lower than about 13 degrees C; said ΔT/Δt is optimized such that said pain caused to said patient is eliminated (or at least alleviated).

It is another object of the present invention to provide the hand-held apparatus as defined above, additionally comprising an aperture through which said strip-needle is adapted to pierce said skin.

It is another object of the present invention to provide the hand-held apparatus as defined above, wherein said actuator activates said strip-needle by means of mechanical actuation or magnetic actuation.

It is another object of the present invention to provide the hand-held apparatus as defined above, wherein said electrochemical sensor is adapted to provide an electrical signal corresponding to said analyte concentration in said blood sample and/or said interstitial fluid. It is another object of the present invention to provide the hand-held apparatus as defined above, additionally comprising a converter adapted to convert said electrical signal provided by said electrochemical sensor into a digital value representing the analyte concentration. It is another object of the present invention to provide the hand-held apparatus as defined above, wherein said analyte is selected from a group consisting of glucose, uric acid, creatinine, calcium, cholesterol, different proteins and triglycerides.

It is another object of the present invention to provide the hand-held apparatus as defined above, wherein said PCCP is adapted for applying pressure Pl on said skin prior to during and/or after piercing thereof by said piercing mechanism; said applied pressure Pl of said PCCP is optimized such that said pain caused by said piercing is eliminated (or at least alleviated).

It is another object of the present invention to provide the hand-held apparatus as defined above, additionally comprising controlling mechanism; wherein said controlling mechanism is adapted to control said depth D, said temperature T,_PC_CP> said time t and said applied pressure Pj₁ said final temperature T_D at depth D; said ΔT/Δt or any combination thereof; further wherein said controlling mechanism is adapted to prevent said final temperature TQ and/or said T,P_CCP from decreasing below about 0 degrees C.

It is another object of the present invention to provide the hand-held apparatus as defined above, additionally comprising a sensors system adapted to prevent piercing of an undesirable area.

It is another object of the present invention to provide the hand-held apparatus as defined above, wherein the prevention is based upon sensed thermal and/or optical and/or electrical conduciveness and/or visual parameters of said skin.

It is another object of the present invention to provide the hand-held apparatus as defined above, additionally comprising a sensor system adapted to sense parameters of said skin. It is another object of the present invention to provide the hand-held apparatus as defined above, wherein said parameters are selected from a group comprising thermal parameters, conductive parameters, visual parameters.

It is another object of the present invention to provide the hand-held apparatus as defined above, additionally comprising (a) a memory into which said analyte concentration is stored; and (b) a communication apparatus adapted to transfer the information sensed by said sensors to any medical personnel.

It is another object of the present invention to provide a method for detecting and quantitating an analyte in blood or interstitial fluid whilst eliminating (or at least alleviating) the pain caused the patient. The method comprises steps selected inter alia form: a. obtaining hand-held apparatus comprising; i. piercing mechanism adapted to pierce said patient's skin, to detect and to quantize said analyte comprising at least one reciprocating strip- needle; said strip needle is adapted to pierce a region of said skin, and to penetrate to depth D in said skin; said depth D is characterized by an initial temperature T; said strip-needle comprising (a) an actuator adapted to activate said strip-needle; and, (b) an electrochemical sensor adapted to indicate the amount of said analyte; ii. at least one displaying unit in communication with said piercing mechanism for displaying said analyte quantity to said patient comprising a display in communication with said electrochemical sensor, and adapted for displaying said analyte amount to said patient; iii. a cooling mechanism adapted to eliminate (or at least alleviate) the pain caused by said piercing to said patient comprising at least one attachable cooling means, especially a Peltier Cooled Cold Plate (PCCP), in connection with a radiator/thermal mass and sufficient DC power supply; said PCCP is characterized by an effective surface area S; said effective surface S is optimized such that said pain caused by said piercing is eliminated (or at least alleviated); said PCCP is characterized by temperature Tipccp, said PCCP adapted for cooling a portion of said skin prior to and/or during and/or after piercing thereof by said piercing mechanism such that the cooling is obtained at said depth D; said depth D is cooled from said initial temperature T to a final temperature T_D (ΔT) in a period of time t (Δt) by said PCCP; said final temperature TQ of said depth D is higher than about 0 and lower than about 13 degrees C; said ΔT/Δt is optimized such that said pain caused to said patient is eliminated (or at least alleviated); b. cooling said PCCP to T_lPCcp; c. placing said cold PCCP on said skin for a period of time t, such that the cooling is obtained at depth D; d. attuning the temperature at said depth D to final temperature TD at said period of time t; said T_D is higher than about 0 and lower than about 13 degrees C; e. piercing said patient skin; f. withdrawing said blood sample and/or said interstitial fluid; g. indicating the amount of said analyte; wherein said step of cooling is eliminating (or at least alleviating) said pain caused to said patient by said step of piercing; further wherein the pain caused by said step of piercing is less than 2 on the SVAS scale. Alternatively, said step of piercing alleviates said pain caused to said patient by at least one stage of the SVAS scale.

It is another object of the present invention to provide the method as defined above, wherein said method additionally comprising step of electrochemically reacting said blood sample and/or said interstitial fluid with said electrochemical sensor.

It is another object of the present invention to provide the method as defined above, wherein said method additionally comprising step of providing an electrical signal corresponding to said analyte concentration. It is another object of the present invention to provide the method as defined above, wherein said method additionally comprising step of converting said electrical signal into a digital value of said analyte concentration.

It is another object of the present invention to provide the method as defined above, wherein said method additionally comprising step of displaying said digital value to said patient. It is another object of the present invention to provide the method as defined above, wherein said method additionally comprising step of applying pressure P₁ on said skin prior to and/or during and/or after said step of piercing.

It is another object of the present invention to provide the method as defined above, wherein said method additionally comprising step of selecting said analyte from a group comprising glucose, uric acid, creatinine, calcium, cholesterol, different proteins and triglycerides. It is another object of the present invention to provide the method as defined above, wherein said method additionally comprising step of preventing said temperature T_D from decreasing below 0 degrees C.

It is another object of the present invention to provide the method as defined above, wherein said method additionally comprising step of controlling said temperature T, said T_JPCCP, said pressure Pl , said final T_D at said depth D₁ said ΔT/Δt.

It is another object of the present invention to provide the method as defined above, wherein said method additionally comprising step of injecting a medicine to said patient. It is another object of the present invention to provide the method as defined above, wherein said method additionally comprising step of withdrawing fluids from said patient. It is another object of the present invention to provide the method as defined above, wherein said method additionally comprising step of preventing piercing of an undesirable area. It is another object of the present invention to provide the method as defined above, additionally comprising steps of (a) storing said analyte concentration; and (b) either online or offline transmitting said concentration to a medical personnel.

It is another object of the present invention to provide a method for encouraging a self injection compliance of a patient. The method comprises steps selected inter alia from: a. obtaining the hand-held apparatus comprising; i. piercing mechanism adapted to pierce said patient's skin, to detect and to quantize said analyte comprising at least one reciprocating strip- needle; said strip needle is adapted to pierce a region of said skin, and to penetrate to depth D in said skin; said depth D is characterized by an initial temperature T; said strip-needle comprising (a) an actuator adapted to activate said strip-needle; and, (b) an electrochemical sensor adapted to indicate the amount of said analyte; ii. at least one displaying unit in communication with said piercing mechanism for displaying said analyte quantity to said patient comprising a display in communication with said electrochemical sensor, and adapted for displaying said analyte amount to said patient; iii. a cooling mechanism adapted to eliminate (or at least alleviate) the pain caused by said piercing to said patient comprising at least one attachable cooling means, especially a Peltier Cooled Cold Plate (PCCP), in connection with a radiator/thermal mass and sufficient DC power supply; said PCCP is characterized by an effective surface area S; said effective surface S is optimized such that said pain caused by said piercing is eliminated (or at least alleviated); said PCCP is characterized by temperature T,_PCCP, said PCCP adapted for cooling a portion of said skin prior to and/or during and/or after piercing thereof by said piercing mechanism such that the cooling is obtained at said depth D; said depth D is cooled from said initial temperature T to a final temperature T_D (ΔT) in a period of time t (Δt) by said PCCP; said final temperature TQ of said depth D is higher than about 0 and lower than about 13 degrees C; said ΔT/Δt is optimized such that said pain caused to said patient is eliminated (or at least alleviated); b. lowering said patient's physiology barrier of piercing; and, c. piercing said patient; wherein said patient will undergo self injection treatment according to a predetermined medical needs.

It is lastly an object of the present invention to provide a method for alleviating needle phobia and/or tension and/or anxiety whilst piercing a patient's skin with an injector. The method comprises step selected inter alia from: a. obtaining the hand-held apparatus comprising; i. piercing mechanism adapted to pierce said patient's skin, to detect and to quantize said analyte comprising at least one reciprocating strip- needle; said strip needle is adapted to pierce a region of said skin, and to penetrate to depth D in said skin; said depth D is characterized by an initial temperature T; said strip-needle comprising (a) an actuator adapted to activate said strip-needle; and, (b) an electrochemical sensor adapted to indicate the amount of said analyte; ii. at least one displaying unit in communication with said piercing mechanism for displaying said analyte quantity to said patient comprising a display in communication with said electrochemical sensor, and adapted for displaying said analyte amount to said patient; iii. a cooling mechanism adapted to eliminate (or at least alleviate) the pain caused by said piercing to said patient comprising at least one attachable cooling means, especially a Peltier Cooled Cold Plate (PCCP), in connection with a radiator/thermal mass and sufficient DC power supply; said PCCP is characterized by an effective surface area S; said effective surface S is optimized such that said pain caused by said piercing is eliminated (or at least alleviated); said PCCP is characterized by temperature Tjp<χp; said PCCP adapted for cooling a portion of said skin prior to and/or during and/or after piercing thereof by said piercing mechanism such that the cooling is obtained at said depth D; said depth D is cooled from said initial temperature T to a final temperature T_D (ΔT) in a period of time t (Δt) by said PCCP; said final temperature T_D of said depth D is higher than about 0 and lower than about 13 degrees C; said ΔT/Δt is optimized such that said pain caused to said patient is eliminated (or at least alleviated); b. cooling said PCCP to TJ_PCCP; c. placing said cold PCCP on said skin for a period of time t, such that the cooling is obtained at depth D; d. attuning the temperature at said depth D to final temperature T_D at said period of time t; said T_D is higher than about 0 and lower than about 13 degrees C; e. lowering said patient's needle phobia barrier and/or said patient's tension and/or said patient's anxiety; and, f. piercing said patient skin. It is another object of the present invention to provide a hand-held apparatus adapted to pierce a region of a patient's skin, to detect and to quantize an analyte in the blood or interstitial fluid; said apparatus comprising: a. piercing mechanism adapted to pierce said patient's skin, comprising at least one reciprocating strip-needle; said strip needle is adapted to pierce a region of said skin, and to penetrate to depth D in said skin; said depth D is characterized by an initial temperature T; said strip-needle comprising (a) an actuator adapted to activate said strip- needle; and, (b) an electrochemical sensor adapted to indicate the amount of said analyte; b. a cooling mechanism adapted to eliminate (or at least alleviate) the pain caused by said piercing to said patient; comprising: at least one attachable cooling means, especially a Peltier Cooled Cold Plate (PCCP), in connection with a radiator/thermal mass and sufficient DC power supply; said PCCP is characterized by an effective surface area S; said effective surface S is optimized such that said pain caused by said piercing is eliminated (or at least alleviated); said PCCP is characterized by temperature Tipccp; said PCCP adapted for cooling a portion of said skin prior to and/or during and/or after piercing thereof by said piercing mechanism such that the cooling is obtained at said depth D; said depth D is cooled from said initial temperature T to a final temperature T_D (ΔT) in a period of time t (Δt) by said PCCP; said final temperature TD of said depth D is higher than about 0 and lower than about 13 degrees C; said ΔT/Δt is optimized such that said pain caused to said patient is eliminated (or at least alleviated). wherein said patient reported pain during said piercing is less than 2 on the SVAS scale; further wherein said patient reported pain during said piercing is alleviated by at least one stage of the SVAS scale.

It is another object of the present invention to provide the hand-held apparatus as defined above, additionally comprising an analyte detector in communication with said electrochemical sensor in said piercing mechanism, adapted to display to said patient's the amount of said analyte. It is another object of the present invention to provide the hand-held apparatus as defined above, additionally comprising an aperture through which said strip-needle is adapted to pierce said skin.

It is another object of the present invention to provide the hand-held apparatus as defined above, wherein said electrochemical sensor is adapted to provide an electrical signal corresponding to said analyte concentration in said blood sample and/or said interstitial fluid.

It is another object of the present invention to provide the hand-held apparatus as defined above, additionally comprising a converter adapted to convert said electrical signal provided by said electrochemical sensor into a digital value representing the analyte concentration.

It is another object of the present invention to provide the hand-held apparatus as defined above, wherein said analyte is selected from a group consisting of glucose, uric acid, creatinine, calcium, cholesterol, different proteins and triglycerides.

It is another object of the present invention to provide the hand-held apparatus as defined above, wherein said PCCP is adapted for applying pressure Pl on said skin prior to during and/or after piercing thereof by said piercing mechanism; said applied pressure Pl of said

PCCP is optimized such that said pain caused by said piercing is eliminated (or at least alleviated).

It is another object of the present invention to provide the hand-held apparatus as defined above, additionally comprising controlling mechanism; wherein said controlling mechanism is adapted to control said depth D, said temperature TJ_PCCP, said time t and said applied pressure P_1; said final temperature T_D at depth D; said ΔT/Δt or any combination thereof; further wherein said controlling mechanism is adapted to prevent said final temperature T_D and/or said TJP_CCP from decreasing below about 0 degrees C.

It is another object of the present invention to provide the hand-held apparatus as defined above, wherein the prevention is based upon sensed thermal and/or optical and/or conductive and/or visual parameters of said skin. It is another object of the present invention to provide the hand-held apparatus as defined above additionally comprising a sensor system adapted to sense parameters of said skin. It is another object of the present invention to provide the hand-held apparatus as defined above, wherein said parameters are selected from a group comprising thermal parameters, conductive parameters, visual parameters.

It is another object of the present invention to provide a method for detecting and quantitating an analyte in blood or interstitial fluid whilst eliminating (or at least alleviating) the pain caused the patient. The method comprises steps selected inter alia from: a. obtaining hand-held apparatus comprising i. piercing mechanism adapted to pierce said patient's skin, comprising at least one reciprocating strip-needle; said strip needle is adapted to pierce a region of said skin, and to penetrate to depth D in said skin; said depth D is characterized by an initial temperature T; said strip- needle comprising (a) an actuator adapted to activate said strip-needle; and, (b) an electrochemical sensor adapted to indicate the amount of said analyte; ii. a cooling mechanism adapted to eliminate (or at least alleviate) the pain caused by said piercing to said patient; comprising at least one attachable cooling means, especially a Peltier Cooled Cold Plate (PCCP), in connection with a radiator/thermal mass and sufficient DC power supply; said PCCP is characterized by an effective surface area S; said effective surface S is optimized such that said pain caused by said piercing is eliminated (or at least alleviated); said PCCP is characterized by temperature T_JPCCP; said PCCP adapted for cooling a portion of said skin prior to and/or during and/or after piercing thereof by said piercing mechanism such that the cooling is obtained at said depth D; said depth D is cooled from said initial temperature T to a final temperature T_D (ΔT) in a period of time t (Δt) by said PCCP; said final temperature T_D of said depth D is higher than about 0 and lower than about 13 degrees C; said ΔT/Δt is optimized such that said pain caused to said patient is eliminated (or at least alleviated); b. cooling said PCCP to T_IPCCP; c. placing said cold PCCP on said skin for a period of time t, such that the cooling is obtained at depth D; d. attuning the temperature at said depth D to final temperature T_D at said period of time t; said TQ is higher than about 0 and lower than about 13 degrees C; and, e. piercing said patient skin; wherein said step of cooling is eliminating (or at least alleviating) said pain caused to said patient by said step of piercing; further wherein said step of piercing is less than 2 on the SVAS scale; further wherein said patient reported pain during said piercing is alleviated by at least one stage of the SVAS scale.

It is another object of the present invention to provide the method as defined above, additionally comprising step of withdrawing said blood sample and/or said interstitial fluid. It is another object of the present invention to provide the method as defined above, additionally comprising steps of introducing said strip-needle into an analyte detector; and, indicating said patient the amount of said analyte.

It is another object of the present invention to provide the method as defined above, wherein said method additionally comprising step of providing an electrical signal corresponding to said analyte concentration.

It is another object of the present invention to provide the method as defined above, wherein said method additionally comprising step of converting said electrical signal into a digital value of said analyte concentration.

It is another object of the present invention to provide the method as defined above, wherein said method additionally comprising step of displaying said digital value to said patient. It is another object of the present invention to provide the method as defined above, wherein said method additionally comprising step of applying pressure P₁ on said skin prior to and/or during and/or after said step of piercing. It is another object of the present invention to provide the method as defined above, wherein said method additionally comprising step of selecting said analyte from a group comprising glucose, uric acid, creatinine, calcium, cholesterol, different proteins and triglycerides. It is another object of the present invention to provide the method as defined above, wherein said method additionally comprising step of preventing said temperature T_D from decreasing below 0 degrees C.

It is another object of the present invention to provide the method as defined above, wherein said method additionally comprising step of controlling said temperature T, said Tipccp_, said pressure Pl, said final T_D at said depth D, said ΔT/Δt.

It is another object of the present invention to provide a method for encouraging a self injection compliance of a patient. The method comprises steps selected inter alia from: a. obtaining the hand-held apparatus comprising; i. piercing mechanism adapted to pierce said patient's skin, comprising at least one reciprocating strip-needle; said strip needle is adapted to pierce a region of said skin, and to penetrate to depth D in said skin; said depth D is characterized by an initial temperature T; said strip- needle comprising (a) an actuator adapted to activate said strip-needle; and, (b) an electrochemical sensor adapted to indicate the amount of said analyte; ii. a cooling mechanism adapted to eliminate (or at least alleviate) the pain caused by said piercing to said patient; comprising at least one attachable cooling means, especially a Peltier Cooled Cold Plate (PCCP), in connection with a radiator/thermal mass and sufficient DC power supply; said PCCP is characterized by an effective surface area S; said effective surface S is optimized such that said pain caused by said piercing is eliminated (or at least alleviated); said PCCP is characterized by temperature T_JPCCP; said PCCP adapted for cooling a portion of said skin prior to and/or during and/or after piercing thereof by said piercing mechanism such that the cooling is obtained at said depth D; said depth D is cooled from said initial temperature T to a final temperature TQ (ΔT) in a period of time t (Δt) by said PCCP; said final temperature T_D of said depth D is higher than about 0 and lower than about 13 degrees C; said ΔT/Δt is optimized such that said pain caused to said patient is eliminated (or at least alleviated); b. lowering said patient's physiology barrier of piercing; and ? (above) c. piercing said patient; wherein said patient will undergo self injection treatment according to a predetermined medical needs.

It is lastly an object of the present invention to provide a method for alleviating needle phobia and/or tension and/or anxiety whilst piercing a patient's skin with an injector. The method comprises steps selected inter alia from: a. obtaining the hand-held apparatus comprising; i. piercing mechanism adapted to pierce said patient's skin, comprising at least one reciprocating strip-needle; said strip needle is adapted to pierce a region of said skin, and to penetrate to depth D in said skin; said depth D is characterized by an initial temperature T; said strip- needle comprising (a) an actuator adapted to activate said strip-needle; and, (b) an electrochemical sensor adapted to indicate the amount of said analyte; ii. a cooling mechanism adapted to eliminate (or at least alleviate) the pain caused by said piercing to said patient; comprising at least one attachable cooling means, especially a Peltier Cooled Cold Plate (PCCP), in connection with a radiator/thermal mass and sufficient DC power supply; said PCCP is characterized by an effective surface area S; said effective surface S is optimized such that said pain caused by said piercing is eliminated (or at least alleviated); said PCCP is characterized by temperature T,pccp_; said PCCP adapted for cooling a portion of said skin prior to and/or during and/or after piercing thereof by said piercing mechanism such that the cooling is obtained at said depth D; said depth D is cooled from said initial temperature T to a final temperature T_D (ΔT) in a period of time t (Δt) by said PCCP; said final temperature T_D of said depth D is higher than about 0 and lower than about 13 degrees C; said ΔT/Δt is optimized such that said pain caused to said patient is eliminated (or at least alleviated); b. cooling said PCCP to Tjpccp; c. placing said cold PCCP on said skin for a period of time t, such that the cooling is obtained at depth D; d. attuning the temperature at said depth D to final temperature T_D at said period of time t; said T_D is higher than about 0 and lower than about 13 degrees C; e. lowering said patient's needle phobia barrier and/or said patient's tension and/or said patient's anxiety; and, f. piercing said patient skin.

BRIEF DESCRIPTION OF THE DRAWINGS

In order to understand the invention and to see how it may be implemented in practice, a plurality of embodiments is adapted to now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which

FIG. 1 is a schematic diagram showing the relationship between the pain caused to the patient and the cooling rate.

FIG. 2 is a schematic drawing showing a plate 10 applying pressure on skin 20.

FIG. 3-5C is an overview of the pain relieving hand help apparatus according to the present invention;

FIG. 6 is a schematic diagram displaying the actuation of the pain relieving hand help apparatus according to the present invention.

FIG. 7 is a three-dimensional schematic diagram of pain relieving hand help apparatus.

FIGS. 8 -11 represent the clinical test results.

FIGS. 12-14 represent thermal experiment results. DETAILED DESCRIPTION OF THE INVENTION

The following description is provided, alongside all chapters of the present invention, so as to enable any person skilled in the art to make use of said invention and sets forth the best modes contemplated by the inventor of carrying out this invention. Various modifications, however, is adapted to remain apparent to those skilled in the art, since the generic principles of the present invention have been defined specifically to provide a pain relieving hand-held apparatus for piercing and/or detection and quantization of an analyte in the blood.

More specifically the present invention provides a device and method that eliminates the pain caused to a patient when said patient is pierced; I.e., the pain caused by the piercing is less than 2 on the SVAS scale.

Alternatively or additionally the present invention provides a device and method that alleviates the pain caused to a patient when said patient is pierced; I.e., the pain caused by the piercing is alleviated by at least one stage of the SVAS scale.

The present invention provides a hand-held apparatus adapted to painlessly pierce a region of a patient's skin, to detect and to quantize an analyte in the blood or interstitial fluid. The apparatus comprising: a. piercing mechanism adapted to pierce the patient's skin, to detect and to quantize the analyte; b. a display unit for displaying the analyte quantity to the patient; and, c. a cooling mechanism adapted to eliminate (or at least alleviate) the pain caused by said piercing to the patient.

The piercing mechanism comprising: i. reciprocating strip-needle; the strip needle is adapted to penetrate to depth D in the skin; depth D is characterized by an initial temperature T; the strip-needle comprising (a) an actuator adapted to activate the strip-needle; and, (b) an electrochemical sensor adapted to indicate the amount of the analyte. The displaying unit comprising: i. a display in communication with the electrochemical sensor, and adapted for displaying the analyte amount to the patient. The cooling mechanism, comprising: i. at least one attachable cooling means, especially a Peltier Cooled Cold Plate

(PCCP), in connection with a radiator/thermal mass and sufficient DC power supply; said PCCP is characterized by an effective surface area S; said effective surface S is optimized such that said pain caused by said piercing is eliminated (or at least alleviated); said PCCP is characterized by temperature Tipccp; said PCCP adapted for cooling a portion of said skin prior to and/or during piercing thereof by said piercing mechanism such that the cooling is obtained at said depth D; said depth D is cooled from said initial temperature T to a final temperature T_D (ΔT) in a period of time t (Δt) by said PCCP; said final temperature TQ of said depth D is higher than about 0 and lower than about 13 degrees C; said ΔT/Δt is optimized such that said pain caused to said patient is eliminated (or at least alleviated).

In other words, the present invention provides a device that when used, the patient reports pain during the piercing to be less than 2 on the SVAS scale.

Alternatively or additionally, the device is especially adapted to alleviate the pain caused to the patient by at least one stage of the SVAS scale.

The present invention also provides a method for detecting and quantitating an analyte in blood or interstitial fluid whilst eliminating (or at least alleviating) the pain caused the patient. The method comprise step selected inter alia from (a) obtaining the hand-held apparatus; (b) cooling the PCCP to temperature T_JPCCP ; (c) placing the cold PCCP on the skin for a period of time t, such that the cooling is obtained at depth D; (d) attuning the temperature at depth D to final temperature T_D; T_D is higher than about 0 and lower than about 13 degrees C; (e) piercing the patient skin; (f) withdrawing a blood sample and/or interstitial fluid; and, (g) indicating the amount of the analyte. The step of cooling and the step of applying pressure are eliminating (or at least alleviating) the pain caused to the patient by the step of piercing. Furthermore the patient reportes pain during said piercing is less than 2 on the SVAS scale. Yet more, the patient reportes pain during said piercing is alleviated by at least one stage of the SVAS scale.

It should be emphasized that according to another embodiment of the present invention, the apparatus 10 comprises only the piercing mechanism 100 and the cooling mechanism 300. In other words, the device is adapted to pierce a region of a patient skin whilst alleviating (or eliminating completely) the pain caused to the patient. Once the strip-needle 120 pierces the patient, the strip-needle 120 is introduced into an analyte detector (e.g., glucometer) adapted to quantify and display to the patient the amounts of analyte detected.

The term "hypodermic needle" refers hereinafter to a hollow needle commonly used with a syringe to inject substances into the subcutaneous. The term "analyte detector" refers hereinafter to any detector adapted to detect and quantify the amount of analyte is there in a sample. One example of an analyte detector is a glucometer.

The term "Sindolor Visual Analogue Scale (SVAS)" refers hereinafter to a measurement that measures the amount of pain a patient feels. The SVAS ranges across a continuum from none to an extreme amount of pain. The SVAS is a straight line, with the left end of the line representing no pain and the right end of the line representing the worst pain. Patients are asked to mark on the line where they think their pain is (see table 1 in example 1).

The term "intramuscular needle" refers hereinafter to a needle that injects a substance directly into a muscle.

The term "Thermoelectric cooling" refers hereinafter to the use of the Peltier effect to create a heat flux between the junction of two different types of materials. A Peltier cooler and/or heater, or thermoelectric heat pump is a solid-state active heat pump which transfers heat from one side of the device to the other side against the temperature gradient (from cold to hot), with consumption of electrical energy.

The term "Cold Plate" refers hereinafter to a heat transport system designed to spread heat and transfer it from its source to the sample or the ambient environment.

The term "Seebeck effect" refers hereinafter to the conversion of temperature differences directly into electricity.

The term "Peltier effect" refers hereinafter to the reverse of the Seebeck effect, i.e, a creation of a heat - temperature difference from an electric voltage. It occurs when a current is passed through two dissimilar metals or semiconductors (n-type and p-type) that are connected to each other at two junctions (Peltier junctions). The current drives a transfer of heat from one junction to the other: one junction cools off while the other heats up. As a result, the effect is often used for thermoelectric cooling.

The term "Peltier Cooled Cold Plate (PCCP)" refers hereinafter to one of the components of a cooling system utilizing thermoelectric coolers (i.e. the peltier effect) to reduce temperatures.

The term "D" refers hereinafter to the depth to which the needle penetrates.

The term "T" refers hereinafter to the initial temperature at depth D.

The term "TD" refers hereinafter to the final temperature at depth D.

The term "TJP_CCP" refers hereinafter to the starting temperature at which the Peltier Cooled

Cold Plate is placed on the skin. The term "starting time" refers hereinafter to the cooling starting time (i.e. the time from which the PCCP is placed on the skin).

The term "finish time" refers hereinafter to the time at which the cooling of depth D was has stopped and the piercing of the patient can begin. In other words, the temperature in depth D had reached temperature T_D

The term "cooling rate" refers hereinafter to the temperature differences between T and TQ

(ΔT) divided by the differences between the starting time and finish time (ΔT/Δt).

The term "Heat capacity (Cp)" refers hereinafter to the measure of the heat energy required to increase/decrease the temperature of an object by a certain temperature interval. Heat capacity is an extensive property because its value is proportional to the density and content of the object.

The term "Compliance" refers hereinafter to a patient both agreeing to and then undergoing some part of his/hers treatment program as advised by his/hers doctor or other healthcare worker.

The term "conductive sensor" refers hereinafter to a sensor that can sense the electrical conductivenes of the skin.

The term "Optic sensor" refers hereinafter to a sensor that can measure optics parameters.

The term "about" refers hereinafter to a range of 25% below or above the referred value.

The term "region of the skin which is undesirable for delivery" refers hereinafter to any region which unwanted or un-recommended for administering a drug or piercing. For example, a region having a bandage and/or a plaster and/or a wound etc. is a region which is undesirable for delivery.

The term "blood sampling" hereinafter refers to an extraction of veinous blood, usually from the arm, followed by a laboratory analysis performed on the blood sample.

The term "glucose meter (or glucometer)" hereinafter refers to a medical device for determining the approximate concentration of glucose in the blood.

The term "electrochemical sensor" hereinafter refers to a device configured to detect the presence and/or measure the level of an analyte in a sample via electrochemical oxidation and reduction reactions on the sensor. These reactions are transduced to an electrical signal that can be correlated to an amount, concentration, or level of an analyte in the sample.

The term "strip-needle" refers hereinafter to a combination of a needle adapted to pierce the patient and measuring means adapted detect and to quantize an analyte. The term "Coulometry" refers hereinafter to the name given to a group of electroanalytical chemistry techniques that determine the amount of matter transformed during an electrolysis reaction by measuring the amount of electricity (in coulombs) consumed or produced. The technique is applicable to redox reactions, which are reactions in which electrons are transferred from one molecule to another. The reaction is controlled by applying an electrical potential and the amount of electricity (i.e, the number of electrons) needed to complete the reaction is the main measurement.

The term "Colorimetry" refers hereinafter to the science that describes colors in numbers, or provides a physical color match using a variety of measurement instruments.

The term "Benzidine" refers hereinafter to 4,4'-diaminobiphenyl.

Before explaining the figures, it should be understood that the invention is not limited in its application to the details of construction and the arrangement of the components set forth in the following description or illustrated in the drawings. The invention can be carried out in various ways.

Reference is now made to Fig. 1 which is a schematic diagram showing the relationship between the pain caused to the patient and the cooling rate. It can be seen from the diagram that both in slow and fast cooling rates a considerable amount of pain is caused to the patient.

It can also be seen from the diagram that there is a point in which the cooling rate causes minimum pain to the patient.

Reference is now made to Fig. 2 which is a schematic drawing showing a plate 10 applying pressure on skin 21. Due to the applied pressure of the pate on the skin the blood flow in the upper layer of the skin 31 is reduced. By reducing the blood flow to the area, the cooling of that area is more efficient. Thus, the mechanoreceptors (which were in a non-activated state

41 prior to applying pressure) are now stimulated 50 and according to the Gate Control

Theory the 'Pain gate' is now at least partially shut. The at least partially shut down of the

'Pain gate' enables the relief of pain through the application of cooling the area.

Reference is now made to Figs. 3-5, showing the hand-held apparatus 10 for the detection and quantization of an analyte in blood or interstitial fluid whilst alleviating pain caused to the patient.

Fig. 3 represents the apparatus (10) when it's closed and fig 4 represents the apparatus when it's open.

Apparatus 10 comprises a piercing mechanism 100, a displaying unit 200 and a cooling mechanism 300. Button 20 on apparatus 10 provides activating/deactivating the apparatus and button 30 triggers the piercing mechanism 100 (not shown in figure 3). Numerical reference 32 indicates the internal part of button 30 which activates the piercing mechanism 100.

The displaying unit 200 comprises a display 40 and a converter 50. The converter is adapted to convert the electrical signal provided by the electrochemical sensor into a digital value representing the analyte concentration. Display 40 is adapted to present the analyte amount

(i.e. concentration) to the patient.

The cooling mechanism 300 comprises a Peltier Cooled Cold Plate (PCCP) 90. PCCP 90 is located at the working face 75 (i.e., the skin facing side) of apparatus 10. PCCP 90 is adapted for cooling a portion of said skin prior to and/or during and/or after piercing.

The cooling plate 90 is cooled to temperature TJ_PCCP prior to placing it on the skin. Once the cooling plate 90 reaches TJP_CCP it is placed on the skin and cools it in a cooling rate which significantly alleviates the pain and discomfort caused to the patient and even eliminates it completely.

As described, prior to the piercing, PCCP 90 is cooled to temperature TJPC_CP- T_JPCCP can vary from about 0 to about 13 degrees. T_JPCCP is determined and optimized by the physical dimensions of the apparatus (length, width and height), the shape of the cross section area, the heat capacity (Cp) and the density. Once the PCCP 90 reaches T_JPCCP it is placed on the skin.

Once the PCCP 90 is placed on the skin, the internal layers (at Depth D) of the skin are cooled from said initial temperature T to a final temperature T_D in a period of time t (Δt). The temperature difference (from the initial temperature to the final temperature) is marked as ΔT_.

Period of time Δt can be varied from a few seconds to a few minutes. Final temperature T_D at depth D is more than about 0 and less than about 13 degrees C.

The cooling rate (ΔT/Δt) is optimized so as the pain caused to the patient is eliminated (or at least alleviated). Furthermore, the cooling rate ΔT/Δt is optimized such that the cooling is obtained at the depth D. In other words, the temperature of depth D had reached T_D-

Moreover, prior to and/or during piercing (and/or after piercing) the patient's skin, the PCCP

90 can additionally apply pressure Pl on the patient's skin such that the pain caused by the piercing would be eliminated (or at least alleviated). Pressure Pl can vary from about 0.2 to about 0.5 Bar.

The PCCP has a cross sectional area ranging about 1.0 square centimeter (not shown). In order to calculate the time needed to reach T_D, a table marked as TST calculates the time needed to cool the skin at depth D, as a function of the initial temperature of the cooling plate from the time of contact with the skin. The table is based on a thermal model. The main parameters used in this model are: Specific heat, Thermal mass, Density and heat transfer coefficient. These parameters relate to two materials: Skin and Blood. Their composition is based on the finger's skin, where the blood flow rate is measured at skin layer, under pressure of bout 0.2 to about 0.5 Bar (in order to slow the free blood flow to the upper layer of the skin). The temperature measuring point that represents the sensing area of the skin layer is at the depth of about 0.3 to about 1 mm from the surface of the skin. The time mentioned in the

TST table is the time increment measured from the moment the cooling disk touches the skin until the temperature at the measuring point reaches about 0 to +13 degrees C. According to one embodiment of the present invention the TST table is designed to be a part of the control system (the detailed process is given in example 2).

The piercing mechanism 100 (as can be seen from figs 4 - 5b), comprises a reciprocating strip-needle 120. The strip needle 120 is placed and submersed in a dedicated location 170

(shown in figure 4). The strip-needle penetrates to depth D in the skin (not shown). Depth D is can vary from about 0.3 to about 1.0 millimeters.

Reference is now made to figures 5, 5a and 5b. Figures 5 and 5a display the apparatus 10 having the strip-needle 120 in its dedicated location.

Reference is now to figures 5b and 5c which display the strip needle 120.

Figure 5b illustrates the different parts which constituent the strip needle 120 and figure5c illustrate the entire assembly.

In general the strip comprises three parts:

1. The basis 120c of the strip denotes as numerical references 151-153;

2. The piercing element 120b denotes as numerical references 140-142; and,

3. An envelope 120a.

The basis 120c comprises at least one electrode 153. An electrochemical sensor 150 come into contact with the blood and is adapted to indicate the amount of the analyte measured. Numerical reference 151 is an isolation cover for the electrodes. Numerical reference 152 denotes the region at which the electrodes are coupled to the connectors (i.e., electrodes 60, see figure 7) of the electrical circuit. The piercing element 120b comprises:

1. An actuator 140 (which the pressing arch) adapted to activate the strip-needle 120; 2. Region 141 which is fixed to the basis 120c, thus attaching the piercing element to the basis; and,

3. The edge 142 of the piercing element 120b.

The envelope 120a covers at least part of the basis 120c and at least part of the piercing element 120b.

As can be seen from the figures, the actuator 140 is a semi-rounded member adapted to activate the strip-needle 120 when button 30 is pressed. Once button 30 is presses, it's internal part 32 is pressing said semi-rounded member 140.

Once the actuator 140 is activated, the piercing element 120b (which is coupled to the basis

120c of the strip-needle 120) is triggered and the edge 142 pierces the patient.

In other words, once the strip-needle 120 is triggered, the piercing element 120b straightens

(i.e. transform from a semi-rounded shape into a linear shape) thus, piercing the patient.

It should be pointed out that the actuator 140 is not limited by its shape (i.e. semi-rounded) and can have any shape and configuration suitable for actuating the strip-needle 120.

Furthermore, the actuation means is not limited to mechanical means (i.e. pressing button 30) and it could be magnetically means or electrical means.

The electrochemical sensor 150 comes into contact with the patient's blood and is embedded in the basis 120c of the strip-needle 120 and provides an electrical signal corresponding to the analyte concentration in the blood sample.

The electrochemical sensor 150 preferably comprises a couple of stripes (probes) for double checking the examination.

The electrical signal is created by an electrochemical reaction. The electrical signal provided by the sensor 150 is transferred through the electrodes to region 152 and then by an array of electrodes 60 and a conducting member 70 to the converter 50 in the displaying unit (see figure 7).

The converter 50 in the displaying unit is preprogrammed to convert the electrical signal provided by the electrochemical sensor into a digital value representing the analyte concentration. The digital value is then displayed to the patient by display 40.

An aperture 13, used for the reciprocal movement of the strip-needle 120, is located at a working face 75 of apparatus 10. The working face 75 of apparatus 10 is defined as the portion which faces the pierced region.

The detection of the analyte by the electrochemical sensor can be done by (i) electrochemical reaction; and, (ii) optical or colorimetric methods. The electrochemical reaction:

In general, the sensor will have a working electrode coated with a non-leachable redox mediator. The redox mediator acts as an electron transfer agent between the analyte and the electrode. In addition, a second electron transfer agent, such as an enzyme, can be added to facilitate the electrooxidation or electroreduction of the analyte. By measuring of the current between the working electrode and a counter or reference electrode, one can know the concentration of the analyte. In other words, the charge passed by this current to or from the analyte is correlated with the amount of analyte in the sample.

Specifically in determining glucose, the electrochemical reaction employs the oxidation of glucose to gluconolactone catalyzed by glucose oxidase. The electrochemical sensor 150 will contain the enzyme - glucose oxidase that is known to catalyze the oxidation of glucose

(glucose oxidase enzyme (GOx) binds to beta-D-glucose (an isomer of the six carbon sugar, glucose) and aids in breaking the sugar down into its metabolites. GOx is a dimeric protein which catalyzes the oxidation of beta-D-glucose into D-glucono-l,5-lactone which then hydrolyzes to gluconic acid).

When this reaction takes place an electrochemical reaction is created and the differences in the current (which is correlated to the concentration of glucose).

A similar reaction can be used. In this reaction another enzyme can be utilize - Glucose

Dehydrogenase (GHD).

The colorimetric methods:

In the colorimetric methods, the reflectances are measured. The change in the reflectance can be correlated to the amount of the analyte.

For example, the sensor can contain a benzidine derivative, which is oxidized to a blue polymer by the hydrogen peroxide formed in the oxidation reaction.

Other methods that can be used are coulometric methods and amperometric methods. The coulometric method is a technique used to define a reaction where the amount of charge measured over a fixed time is measured. The amperometric method is used by some meters that allows the reaction to go to completion and where the total charge transfer is measured.

The coulometric method allows for a fixed test time, whereas test times with a meter using the amperometric techique can vary.

As can be seen from figure 4, the apparatus is energized by batteries 80, but it should be pointed out that apparatus 10 can be energized by any other power supply.

Reference is now made to Fig. 6, which is a schematic diagram displaying the actuation of the pain relieving hand help apparatus according to the present invention. The activation of the apparatus is as follows: first, the switching-on button 20 is pressed. By pressing on button 20 the cooling mechanism (e.g. the PCCP 90) is cooled to temperature Tipccp and then placed upon the skin. Now the internal layers (at Depth D) of the skin are cooled from said initial temperature T to a final temperature T_D in a period of time t (Δt). The temperature difference (from the initial temperature to the final temperature) is marked as ΔT_. Period of time Δt can be varied from a few seconds to a few minutes. Final temperature T_D at depth D is more than about 0 and less than about 13 degrees C. The cooling rate (ΔT/Δt) is optimized so as the pain caused to the patient is eliminated (or at least alleviated). Furthermore, the cooling rate ΔT/Δt is optimized such that the cooling is obtained at the depth D. The time needed to reach T_D is calculated by the table TST.

Once the PCCP 90 has reached the desired temperature, placed upon the skin, and a waiting period of time Δt (according to the TST table) had pasted, the semi-rounded member 140 is activated ( by electrical means, magnetic means or mechanic means as will be described hereinafter) by pressing button 30. Thus, the strip-needle 120 is activate (i.e., the piercing member 120b is straightened) and is now able to protrude through port 13 and pierce the patient (i.e., the sharp edge 142 pierces the patient's skin).

Blood from the created opening (not shown) comes into contact with the electrochemical sensor 150. An electrical signal proportional to the analyte concentration in the patient's blood is generated by the electrochemical sensor 150. The electrochemical sensor provides the electrical signal to the controller 50 preprogrammed to convert this signal to a digital value. The digital value of the analyte concentration is then displayed to the patient by display 40.

Reference is now made to Fig. 7, showing a 3-D schematic diagram of the apparatus 10. The electrical signal provided by the sensor 150 (not shown) is transferred to region 152 and then by an array of electrodes 60 and then conducted by a conducting member 70 to the converter 50 in the displaying unit. The converter 50 is preprogrammed to convert the electrical signal provided by the electrochemical sensor into the digital value which represents the analyte concentration. Then, display 40 displays the digital value to the patient. According to another embodiment of the present invention, the apparatus 10 additionally comprises sensor system. Said sensor system adapted to sense a thermal parameter associated with cooling skin. The sensor system may include one or more temperature sensors that are, for example embedded in the PCCP 90. The sensors can be thermocouple or thermistor, e.g., either a positive temperature coefficient (PTC) or negative temperature coefficient (NTC) thermistor, for sensing the temperature of PCCP 90 near skin. The temperature sensor may be connected to a microprocessor that interprets the temperature sensed by the sensor and signals the medical practitioner if there is sufficient cooling for virtually painless piercing. For example, the sensor system may be preset such that if the temperature of the PCCP 90 is at a predetermined (or selectively programmed) value, then a green "GO" light may light or flash to indicate that one may substantially painlessly pierce the patient. This predetermined (or selectively programmed) value is can be on the temperature of the PCCP 90 or on the temperature of the skin. If the predetermined value relies on the temperature of the skin 21 - thermal losses due to, inter alia, thermal contact resistance between plate 90 and skin are taken into account. Conversely, if the critical temperature (on the PCCP) has not yet been reached, then a red "NO GO" light may light or flash to indicate that one should not yet pierce. Alternatively, voice sensors may be used. The sensor system may be connected to the TST table mentioned above, such that a green "GO" light will light once the PCCP 90 has reached the desired temperature. The piercing will initiate once the "GO" light will light and a waiting period of time Δt (according to the TST table) had past.

According to another embodiment, a red "NO GO" light will light if after a period of at least one minute the PCCP had not reached the desired temperature.

Sensor system may comprise other sensors as well. For example, there may be a pressure contact sensor, which may indicate if the PCCP 90 is properly pressed against skin. Thermal contact sensor may comprise a spring or other equivalent biasing device, which senses a force that urges the PCCP against skin. If the force is at a predetermined (or selectively programmed) value, then green "GO" light may light or flash, indicating that the operation (i.e. the piercing) is permissible. Conversely, if the force is below this value, then red "NO GO" light may light or flash to indicate that one should not yet pierce the patient. Another indication for a physical contact between the PCCP and the skin is the fact that the temperature of the PCCP raises as demonstrated and explained in example 3. The sensor system may comprise other sensors as well. For example, there may be a contact sensor which may indicate the amount of pressure applied on the skin. According to another embodiment of the present invention, the apparatus will comprise means allowing the selection of the depth D into which the strip-needle will penetrate. According to another embodiment of the present invention, the apparatus will comprise a memory, such as a non- volatile memory, e.g., flash memory or EEPROM (electrically erasable, programmable read only memory), into which different parameters associated with the glucose-examination are stored. The memory may also comprise any suitable memory medium, such as a floppy disk, smart card or flash memory card, such as an MMC (Multi

Media Card, e.g., made by Siemens/SanDisk), or an SSFDC (Solid State Floppy Disk Card) also called a Smart Media Card (SMC, e.g., made by Toshiba).

The apparatus may comprise communication apparatus, such as a transceiver, adapted to communicate any information or data sensed by any of the sensor systems of the invention to any medical personnel.

Medical information sensed by the apparatus may be communicated to medical personnel.

For example, the information may be sent on-line (via the internet) to a personal computer

(PC) of medical personnel via the Internet or cellular communications and the like.

Information may be sent automatically (after a certain time interval or after a certain number of medical activities, for example) or by download request of a doctor (with or without consent of the patient), for example.

According to another embodiment of the present invention the apparatus additionally comprises a sensors adapted to prevent piercing of an undesirable area. The prevention will be done by thermal, optics, electrical conduction, or visual means.

According to yet another embodiment of the present invention, the apparatus additionally comprises means adapted to apply vibrations whilst heating prior to and/or during and/or after the piercing so as to eliminate (or at least alleviate) the pain.

In the foregoing description, embodiments of the invention, including preferred embodiments, have been presented for the purpose of illustration and description. They are not intended to be exhaustive or to limit the invention to the precise form disclosed. Obvious modifications or variations are possible in light of the above teachings. The embodiments were chosen and described to provide the best illustration of the principals of the invention and its practical application, and to enable one of ordinary skill in the art to utilize the invention in various embodiments and with various modifications as are suited to the particular use contemplated. All such modifications and variations are within the scope of the invention as determined by the appended claims when interpreted in accordance with the breadth they are fairly, legally, and equitably entitled.

EXAMPLES

Examples are given in order to prove the embodiments claimed in the present invention. The example, which is a clinical test, describes the manner and process of the present invention and set forth the best mode contemplated by the inventors for carrying out the invention, but are not to be construed as limiting the invention.

EXAMPLE 1

A clinical test was performed in which:

The objective of the test was to prove that the apparatus according to the present invention is a pain-free apparatus (i.e. it successfully prevents pain inflicted by needle prick injuries caused by injections in healthy volunteers).

Injections with a non-chemical local anesthesia (i.e. the cooling), using an injector based on

EZ-Ject technology were performed.

In the test 41 healthy adult volunteers have participated in the study.

Each one has been injected two sub-cutaneous injections:

• First Injection - no local anesthesia of the skin,

• Second Injection: with anesthesia of the skin.

At the end of the injections each volunteer has to complete a form indicating the pain scale and any side effects.

The test Results:

All volunteers got the two injections and completed the questionnaire on pain scale and side effects. The pain scale range from 1 to 10.

The following table (table 1) represent the SVAS pain scale measuring and the meaning of each stage:

Table 1 scale measuring

1 1.3 2.5 3.5 4.5 5.5 6.5 7.5 8.5 9 9.5 IQ

!

The following table (table 2) represent the questionnaire given to each patient:

Table 2 Questionnaire

The following table (table 3) represents the questionnaire given to the patients after the first injection (i.e. without anesthesia)

Table 3 questionnaire given to the patients after the first injection

The following table (table 4) represents the questionnaire given to the patients before and after the injection. The injection was performed by using the automatic injection system with the anesthetic (i.e. cooling) system.

Table 4 questionnaire given to the patients before and after the injection

The following table (table 5) describes the test results in terms of the pain stage and the amount of patients (i.e. volunteers) in each stage in the first injection and in the second injection.

Table 5 Test results

SUMMARY OF THE RESULTS

Reference is now made to figures 8, which represent the pain level in the two injections; figure 9, which represents the pain differences between the injections; figure 10, which represents the side effects of the injection without anesthesia; and figure 11, which represents the side effects of the injection with anesthesia. 1. Pain

At the injection with local anesthesia (i.e. the cooling) 2 volunteers, out of 41 (5%), have reported a very slight pain. In comparison, at the injection without cooling 28 volunteers, out of 41 (68%), have reported a feeling of pain ate various degrees. This difference is statistically significant.

It should be noted that 6 volunteers in both injections (with and without cooling the skin) have reported "almost pain", which is grade 2 on the pain scale, where 1 is no pain at all and 10 is a very strong pain. 1. Side Effects No difference in side effects has been observed between the two injections types.

The appearance of a little blood drop at the injection site has been observed after the injection with skin cooling in 5 volunteers, while it has been observed in 11 volunteers in the injection without the cooling.

This difference is not statistically significant. Conclusions:

The study demonstrates, without any doubt, that the injection system with a local cooling of the skin reduces significantly the pain level at the injection site without causing any unusual side effects.

EXAMPLE 2 The controlling system.

A table marked TST is designed to be a part of the control system. The table is based on a thermal model. The main parameters used in this model are: Specific heat, Thermal mass, Density and heat transfer coefficient. These parameters relate to materials like: Skin, fat, flash and Blood. Their composition is based on the finger's skin, where the blood flow rate is measured at skin layer, under pressure of bout 0.2 to about 0.5 Bar (in order to slow the free blood flow to the upper layer of the skin). The temperature measuring point that represents the sensing area of the skin layer is at the depth of about 0.3 to about 1 mm from the surface of the skin. The time mentioned in the TST table is the time increment measured from the moment the cooling disk touches the skin until the temperature at the measuring point reaches about 8 to 13 degrees C. The table marked TST calculates the time needed to cool the skin with skin temperature, as a function of the initial temperature of the cooling disk at the moment of contact with the skin. The cooling control system measures the temperature of the cooling disk every half-second and keeps the results of the current and former measurements. Namely, in the memory two temperatures are always kept - the current temperature and the temperature previously measured. The process steps: a) When the measuring temperature of the cooling disc is below 5 C₅ and the temperature measurement shows a definite rising pattern, that is - the temperature at measurement N+l is obviously higher than the temperature at measurement N - the control system gets a signal that the cooling disc is attached to the skin. b) When the control system gets the attachment (of the cooling disc to the skin) signal, the temperature of the cooling disc is registered in the control system. The control system refers this temperature to the TST table. From this table, the control system receives the needed time interval between receiving the attachment signal and the operating of the insertion system, c) At the end of the time interval given by table TST, the control system initiates the signal that starts the operation of the insertion system.

As mentioned, the table is based on thermal calculation as a function of time, by a thermal model half-infinite. The model describes a combine human skin tissue, which is multi-layered and includes: skin layer, fat layer and thick flash layer. The last layer of flash is in fact a very deep layer, and in the model it is described as half-infinite. That is, a thermal layer in which the lower end maintains a constant temperature, regardless of the skin temperature. Each layer is thermally described by a number of major parameters, such as sensible heat coefficient, three dimensional heat transfer coefficients, thermal mass and density. The values of these parameters for the skin layer containing the blood vessels were represent a condition of a small amount of blood reduced flow. In practice, the blood flow in the layer is stopped by an external pressure - the edge of the cooling disk presses the skin at 0.2 - 0.5 Bar.

At the center of the model, over the skin, lays a copper disk of a defined mass. Its shape and dimensions are identical with the system disk described in the patent.

The temperatures measured at the following points were determined as the thermal values describing the model results, under certain, pre-determined conditions : at the cooling disk and at depth of 0, 1, 2, 3, 4, and 5 mm from skin surface (on a perpendicular line from the cooling disk). These values are obtained as a function of their measuring time, in 0.5 sec intervals.

The following parameters were determined as the initial conditions for the cooling system in running the model:

1. Initial temperatures of the disk in values of -2, 0, 2, 4, and 6 C and initial temperature of the skin layer in values of 33, 35, and 37 C.

2. The duration of time in which the disk is cooled after the initiation of the skin cooling process, in values of 0, 3, 5, 8, and 11 sec.

Running of the Model:

1. The initial conditions of the system were determined: environment temperature, whole skin tissue temperature, disk temperature, and the time duration for cooling of the disk in constant power.

2. Running was performed for 20 seconds. 3. A table of the temperature running results was created. The temperatures were taken in intervals of 0.5 sec, at the following points: disk temperature and tissue temperature in six points of measurements.

4. Temperature of the disk had been repeatedly changed up to, and including, the disk maximal temperature and steps 1, 2, 3, 4, were repeated.

5. Skin temperature had been repeatedly changed up to, and including, the tissue maximal temperature and steps 1, 2, 3, 4, were repeated.

6. The duration of time in which the disk is cooled after the initiation of the skin tissue cooling process had been repeatedly changed up to, and including, the maximal time duration and steps 1, 2, 3, 4, were repeated.

A total of 75 runs of the model had been performed and the results were calculated and put into a table, TST. The table supplies the time by which a certain temperature of the skin tissue, at a certain depth, is reached, as a function of three conditions: disk temperature at the time of attachment to the skin, skin temperature at the beginning of the cooling process and the duration of time in which the cooling system continues to cool the disk. A temperature of X C at depth of 2 mm was chosen, while the depth of skin temperature measuring point, skin temperature at that point and the duration of time in which the cooling system continues to cool the disk has been defined as constants. Thus, the TST table supplies the time duration in which a temperature of X C at a depth of 2 mm is achieved, as a function of the disk's temperature at the moment of attachment to the skin.

As a conclusion, the following takes place: when the signal for the attachment of the cooling disk to the skin is received, the control program notes the temperature of the disk, goes to the TST table (located in the control system) and receives from it the exact period of time between the attachment of the disk to the skin and the operation of needle insertion mechanism. With the termination of that period of time, and by a signal from the control system, the needle insertion mechanism will be operated.

EXAMPLE 3

Skin temperature experiments:

A thermal experiment of the injector was conducted as follows:

1. The injector was activated.

2. Once the PCCP had reached the programmed (i.e. pre-determined) temperature, the injector was attached to the skin.

3. A few seconds later, the piercing mechanism was activated. 4. 15 seconds after the piercing, the injector was removed. In the experiment, 5 temperatures' were measured: a. Sensor 1 - the PCCP's temperature. b. Sensor 2 - the temperature of the radiator/thermal mass which is closed to the PCCP. c. Sensor 3 - the temperature of the radiator/thermal mass which is far away from the PCCP. d. Sensor 4 - the PCCP's temperature, underneath the isolation layer. e. Sensor 5 - the skin temperature (about 0.5mm under the surface). 3 experiments were conducted:

1. The cooling plate was centralized with respect to the needle (fig. 12).

2. The cooling plate was centralized with respect to the needle (fig. 13), repetition of " 1 ".

3. The cooling plate was shifted aside with respect to the needle (fig. 14).

All three figures 12-14 illustrate the temperature vs. time dependency, in which channel 1 represents the PCCP's temperature, channel 2 represents temperature of the radiator/thermal mass which is closed to the PCCP, channel 3 represents the temperature of the radiator/thermal mass which is far away from the PCCP, channel 4 represents the PCCP's temperature, underneath the isolation layer and channel 5 represents the skin temperature (about 0.5mm under the surface).

As can be seen from the figures, the PCCP had reached the desired temperature (about 0 degrees C) after 80 sec from the beginning of the experiment. Now the PCCP was pressed against the skin (this is the reason for the constant temperature of the skin layer 0.5mm under the surface). Once the PCCP is placed on the skin, the skin's temperature had decreased and the PCCP's temperature had risen. In all three figures the radiator/thermal mass's temperature had climbed up to the point of the piercing (approximately 90 sec from the beginning).

Claims

1. A hand-held apparatus adapted to pierce a region of a patient's skin, to detect and to quantize an analyte in the blood or interstitial fluid; wherein said apparatus comprising: a. piercing mechanism adapted to pierce said patient's skin, to detect and to quantize said analyte; b. at least one displaying unit in communication with said piercing mechanism for displaying said analyte quantity to said patient; and, c. a cooling mechanism adapted to eliminate the pain caused by said piercing to said patient; further wherein said patient reported pain during said piercing is less than 2 on the SVAS scale.

2. The hand-held apparatus according to claim 1, wherein said piercing mechanism comprises: at least one reciprocating strip-needle; said strip needle is adapted to pierce a region of said skin, and to penetrate to depth D in said skin; said depth D is characterized by an initial temperature T; said strip-needle comprising (a) an actuator adapted to activate said strip- needle; and, (b) an electrochemical sensor adapted to indicate the amount of said analyte; said displaying unit comprising: i. a display in communication with said electrochemical sensor, and adapted for displaying said analyte amount to said patient; said cooling mechanism, comprising: i. at least one attachable cooling means, especially a Peltier Cooled Cold Plate (PCCP), in connection with a radiator/thermal mass and DC power supply; said PCCP is characterized by an effective surface area S; said effective surface S is optimized such that said pain caused by said piercing is eliminated; said PCCP is characterized by temperature Tipccp; said PCCP adapted for cooling a portion of said skin prior to and/or during and/or after piercing thereof by said piercing mechanism such that the cooling is obtained at said depth D; said depth D is cooled from said initial temperature T to a final temperature T_D (ΔT) in a period of time t (Δt) by said PCCP; said final temperature T_D of said depth D is higher than about 0 and lower than about

13 degrees C; said ΔT/Δt is optimized such that said pain caused to said patient is eliminated; further wherein said patient reported pain during said piercing is alleviated by a least on stage of the SVAS scale.

3. The hand-held apparatus according to claim 2, additionally comprising an aperture through which said strip-needle is adapted to pierce said skin.

4. The hand-held apparatus according to claim 3, wherein said actuator activates said strip-needle by means of mechanical actuation or magnetic actuation.

5. The hand-held apparatus according to claim 4, wherein said electrochemical sensor is adapted to provide an electrical signal corresponding to said analyte concentration in said blood sample and/or said interstitial fluid.

6. The hand-held apparatus according to claim 5, additionally comprising a converter adapted to convert said electrical signal provided by said electrochemical sensor into a digital value representing the analyte concentration.

7. The hand-held apparatus according to claim 6, wherein said analyte is selected from a group consisting of glucose, uric acid, creatinine, calcium, cholesterol, different proteins and triglycerides.

8. The hand-held apparatus according to claim 6, wherein said PCCP is adapted for applying pressure Pl on said skin prior to during and/or after piercing thereof by said piercing mechanism; said applied pressure Pl of said PCCP is optimized such that said pain caused by said piercing is eliminated.

9. The hand-held apparatus according to claim 6, additionally comprising controlling mechanism; wherein said controlling mechanism is adapted to control said depth D, said temperature T_JPCCP, said time t and said applied pressure P_1; said final temperature T_D at depth D; said ΔT/Δt or any combination thereof; further wherein said controlling mechanism is adapted to prevent said final temperature T_D and/or said T_JPCCP from decreasing below about 0 degrees C.

10. The hand-held apparatus according to claim 6, additionally comprising a sensors system adapted to prevent piercing of an undesirable area.

11. The hand-held apparatus according to claim 10, wherein the prevention is based upon sensed thermal and/or optical and/or conductive and/or visual parameters of said skin.

12. The hand-held apparatus according to claim 6, additionally comprising a sensor system adapted to sense parameters of said skin.

13. The hand-held apparatus according to claim 12, wherein said parameters are selected from a group comprising thermal parameters, conductive parameters, visual parameters.

14. The hand-held apparatus according to claim 6, additionally comprising (a) a memory into which said analyte concentration is stored; and (b) a communication apparatus adapted to transfer the information sensed by said sensors to any medical personnel.

15. A method for detecting and quantitating an analyte in blood or interstitial fluid whilst eliminating the pain caused the patient; said method comprising steps of: a. obtaining hand-held apparatus comprising: i. piercing mechanism adapted to pierce said patient's skin, to detect and to quantize said analyte comprising at least one reciprocating strip- needle; said strip needle is adapted to pierce a region of said skin, and to penetrate to depth D in said skin; said depth D is characterized by an initial temperature T; said strip-needle comprising (a) an actuator adapted to activate said strip-needle; and, (b) an electrochemical sensor adapted to indicate the amount of said analyte; ii. at least one displaying unit in communication with said piercing mechanism for displaying said analyte quantity to said patient comprising a display in communication with said electrochemical sensor, and adapted for displaying said analyte amount to said patient; iii. a cooling mechanism adapted to eliminate the pain caused by said piercing to said patient comprising at least one attachable cooling means, especially a Peltier Cooled Cold Plate (PCCP), in connection with a radiator/thermal mass and DC power supply; said PCCP is characterized by an effective surface area S; said effective surface S is optimized such that said pain caused by said piercing is eliminated; said PCCP is characterized by temperature T_JPCCP; said PCCP adapted for cooling a portion of said skin prior to and/or during and/or after piercing thereof by said piercing mechanism such that the cooling is obtained at said depth D; said depth D is cooled from said initial temperature T to a final temperature TQ (ΔT) in a period of time t (Δt) by said PCCP; said final temperature T_D of said depth D is higher than about 0 and lower than about 13 degrees C; said ΔT/Δt is optimized such that said pain caused to said patient is eliminated; b. cooling said PCCP to TJ_PCCP; c. placing said cold PCCP on said skin for a period of time t, such that the cooling is obtained at depth D; d. attuning the temperature at said depth D to final temperature T_D at said period of time t; said T_D is higher than about 0 and lower than about 13 degrees C; e. piercing said patient skin; f. withdrawing said blood sample and/or said interstitial fluid; g. indicating the amount of said analyte; wherein said step of cooling is eliminating said pain caused to said patient by said step of piercing; further wherein the pain caused by said step of piercing is less than 2 on the SVAS scale.

16. The method according to claim 15, wherein the pain caused by said step of piercing is alleviated by at least one stage of the SVAS scale.

17. The method according to claim 15, wherein said method additionally comprising step of electrochemically reacting said blood sample and/or said interstitial fluid with said electrochemical sensor.

18. The method according to claim 17, wherein said method additionally comprising step of providing an electrical signal corresponding to said analyte concentration.

19. The method according to claim 18, wherein said method additionally comprising step of converting said electrical signal into a digital value of said analyte concentration.

20. The method according to claim 19, wherein said method additionally comprising step of displaying said digital value to said patient.

21. The method according to claim 15, wherein said method additionally comprising step of applying pressure P₁ on said skin prior to and/or during and/or after said step of piercing.

22. The method according to claim 15, wherein said method additionally comprising step of selecting said analyte from a group comprising glucose, uric acid, creatinine, calcium, cholesterol, different proteins and triglycerides.

23. The method according to claim 15, wherein said method additionally comprising step of preventing said temperature T_D from decreasing below 0 degrees C.

24. The method according to claim 15, wherein said method additionally comprising step of controlling said temperature T, said T,_PCCP, said pressure Pl, said final TD at said depth D_, said ΔT/Δt.

25. The method according to claim 15, wherein said method additionally comprising step of injecting a medicine to said patient.

26. The method according to claim 15, wherein said method additionally comprising step of withdrawing fluids from said patient.

27. The method according to claim 15, wherein said method additionally comprising step of preventing piercing of an undesirable area.

28. The method according to claim 15, additionally comprising steps of (a) storing said analyte concentration; and (b) either online or offline transmitting said concentration to a medical personnel.

29. A method for encouraging a self injection compliance of a patient; said method comprising steps of: a. obtaining the hand-held apparatus comprising; i. piercing mechanism adapted to pierce said patient's skin, to detect and to quantize said analyte comprising at least one reciprocating strip- needle; said strip needle is adapted to pierce a region of said skin, and to penetrate to depth D in said skin; said depth D is characterized by an initial temperature T; said strip-needle comprising (a) an actuator adapted to activate said strip-needle; and, (b) an electrochemical sensor adapted to indicate the amount of said analyte; ii. at least one displaying unit in communication with said piercing mechanism for displaying said analyte quantity to said patient comprising a display in communication with said electrochemical sensor, and adapted for displaying said analyte amount to said patient; iii. a cooling mechanism adapted to eliminate the pain caused by said piercing to said patient comprising at least one attachable cooling means, especially a Peltier Cooled Cold Plate (PCCP), in connection with a radiator/thermal mass and DC power supply; said PCCP is characterized by an effective surface area S; said effective surface S is optimized such that said pain caused by said piercing is eliminated; said PCCP is characterized by temperature T,_PCCP, said PCCP adapted for cooling a portion of said skin prior to and/or during and/or after piercing thereof by said piercing mechanism such that the cooling is obtained at said depth D; said depth D is cooled from said initial temperature T to a final temperature T_D (ΔT) in a period of time t (Δt) by said PCCP; said final temperature T_D of said depth D is higher than about 0 and lower than about 13 degrees C; said ΔT/Δt is optimized such that said pain caused to said patient is eliminated; b. lowering said patient's physiology barrier of piercing; and alleviating needle phobia and/or tension and/or anxiety c. piercing said patient; wherein said patient will undergo self injection treatment according to a predetermined medical needs.

30. A method for alleviating needle phobia and/or tension and/or anxiety whilst piercing a patient's skin with an injector, comprising steps of: a. obtaining the hand-held apparatus comprising; i. piercing mechanism adapted to pierce said patient's skin, to detect and to quantize said analyte comprising at least one reciprocating strip- needle; said strip needle is adapted to pierce a region of said skin, and to penetrate to depth D in said skin; said depth D is characterized by an initial temperature T; said strip-needle comprising (a) an actuator adapted to activate said strip-needle; and, (b) an electrochemical sensor adapted to indicate the amount of said analyte; ii. at least one displaying unit in communication with said piercing mechanism for displaying said analyte quantity to said patient comprising a display in communication with said electrochemical sensor, and adapted for displaying said analyte amount to said patient; iii. a cooling mechanism adapted to eliminate the pain caused by said piercing to said patient comprising at least one attachable cooling means, especially a Peltier Cooled Cold Plate (PCCP), in connection with a radiator/thermal mass and DC power supply; said PCCP is characterized by an effective surface area S; said effective surface S is optimized such that said pain caused by said piercing is eliminated; said PCCP is characterized by temperature T_JPCCP; said PCCP adapted for cooling a portion of said skin prior to and/or during and/or after piercing thereof by said piercing mechanism such that the cooling is obtained at said depth D; said depth D is cooled from said initial temperature T to a final temperature T_D (ΔT) in a period of time t (Δt) by said PCCP; said final temperature T_D of said depth D is higher than about 0 and lower than about 13 degrees C; said ΔT/Δt is optimized such that said pain caused to said patient is eliminated; b. cooling said PCCP to TJPC_CP; c. placing said cold PCCP on said skin for a period of time t, such that the cooling is obtained at depth D; d. attuning the temperature at said depth D to final temperature T_D at said period of time t; said T_D is higher than about 0 and lower than about 13 degrees C; e. lowering said patient's needle phobia barrier and/or said patient's tension and/or said patient's anxiety; and, f. piercing said patient skin.

31. A hand-held apparatus adapted to pierce a region of a patient's skin, to detect and to quantize an analyte in the blood or interstitial fluid; said apparatus comprising: a. piercing mechanism adapted to pierce said patient's skin, comprising at least one reciprocating strip-needle; said strip needle is adapted to pierce a region of said skin, and to penetrate to depth D in said skin; said depth D is characterized by an initial temperature T; said strip-needle comprising (a) an actuator adapted to activate said strip- needle; and, (b) an electrochemical sensor adapted to indicate the amount of said analyte; b. a cooling mechanism adapted to eliminate the pain caused by said piercing to said patient; comprising: at least one attachable cooling means, especially a Peltier Cooled Cold Plate (PCCP), in connection with a radiator/thermal mass and DC power supply; said PCCP is characterized by an effective surface area S; said effective surface S is optimized such that said pain caused by said piercing is eliminated; said PCCP is characterized by temperature T_JPCCP; said PCCP adapted for cooling a portion of said skin prior to and/or during and/or after piercing thereof by said piercing mechanism such that the cooling is obtained at said depth D; said depth D is cooled from said initial temperature T to a final temperature T_D

(ΔT) in a period of time t (Δt) by said PCCP; said final temperature Tp of said depth D is higher than about 0 and lower than about 13 degrees C; said ΔT/Δt is optimized such that said pain caused to said patient is eliminated. wherein said patient reported pain during said piercing is less than 2 on the SVAS scale.

32. The hand-held apparatus according to claim 31, wherein said patient reported pain during said piercing is alleviated by at least one stage on the SVAS scale.

33. The hand-held apparatus according to claim 31, additionally comprising an analyte detector in communication with said electrochemical sensor in said piercing mechanism, adapted to display to said patient's the amount of said analyte.

34. The hand-held apparatus according to either one of claims 31 -33, additionally comprising an aperture through which said strip-needle is adapted to pierce said skin.

35. The hand-held apparatus according to either one of claims 31 -33, wherein said actuator activates said strip-needle by means of mechanical actuation or magnetic actuation.

36. The hand-held apparatus according to either one of claims 31 -33, wherein said electrochemical sensor is adapted to provide an electrical signal corresponding to said analyte concentration in said blood sample and/or said interstitial fluid.

37. The hand-held apparatus according to either one of claims 31 -33, additionally comprising a converter adapted to convert said electrical signal provided by said electrochemical sensor into a digital value representing the analyte concentration.

38. The hand-held apparatus according to either one of claims 31 -33, wherein said analyte is selected from a group consisting of glucose, uric acid, creatinine, calcium, cholesterol, different proteins and triglycerides.

39. The hand-held apparatus according to either one of claims 31 -33, wherein said PCCP is adapted for applying pressure Pl on said skin prior to during and/or after piercing thereof by said piercing mechanism; said applied pressure Pl of said PCCP is optimized such that said pain caused by said piercing is eliminated.

40. The hand-held apparatus according to either one of claims 31 -33, additionally comprising controlling mechanism; wherein said controlling mechanism is adapted to control said depth D, said temperature Tipccp, said time t and said applied pressure P_{1 ;} said final temperature T_D at depth D; said ΔT/Δt or any combination thereof; further wherein said controlling mechanism is adapted to prevent said final temperature T_D and/or said T_JPCCP from decreasing below about 0 degrees C.

41. The hand-held apparatus according to either one of claims 31-33, additionally comprising a sensors system adapted to prevent piercing of an undesirable area.

42. The hand-held apparatus according to claim 39, wherein the prevention is based upon sensed thermal and/or optical and/or conductive and/or visual parameters of said skin.

43. The hand-held apparatus according to either one of claims 31 -33, additionally comprising a sensor system adapted to sense parameters of said skin.

44. The hand-held apparatus according to claim 43, wherein said parameters are selected from a group comprising thermal parameters, conductive parameters, visual parameters.

45. The hand-held apparatus according to either one of claims 43 - 45, additionally comprising (a) a memory into which said analyte concentration is stored; and (b) a communication apparatus adapted to transfer the information sensed by said sensors to any medical personnel.

46. A method for detecting and quantitating an analyte in blood or interstitial fluid whilst eliminating the pain caused the patient; said method comprising steps of: a. obtaining hand-held apparatus comprising i. piercing mechanism adapted to pierce said patient's skin, comprising at least one reciprocating strip-needle; said strip needle is adapted to pierce a region of said skin, and to penetrate to depth D in said skin; said depth D is characterized by an initial temperature T; said strip- needle comprising (a) an actuator adapted to activate said strip-needle; and, (b) an electrochemical sensor adapted to indicate the amount of said analyte; ii. a cooling mechanism adapted to eliminate the pain caused by said piercing to said patient; comprising at least one attachable cooling means, especially a Peltier Cooled Cold Plate (PCCP), in connection with a radiator/thermal mass and DC power supply; said PCCP is characterized by an effective surface area S; said effective surface S is optimized such that said pain caused by said piercing is eliminated; said PCCP is characterized by temperature Tipccp, said PCCP adapted for cooling a portion of said skin prior to and/or during and/or after piercing thereof by said piercing mechanism such that the cooling is obtained at said depth D; said depth D is cooled from said initial temperature T to a final temperature TQ (ΔT) in a period of time t (Δt) by said PCCP; said final temperature TQ of said depth D is higher than about 0 and lower than about 13 degrees C; said ΔT/Δt is optimized such that said pain caused to said patient is eliminated; b. cooling said PCCP to Tipccp; c. placing said cold PCCP on said skin for a period of time t, such that the cooling is obtained at depth D; d. attuning the temperature at said depth D to final temperature TQ at said period of time t; said TD is higher than about 0 and lower than about 13 degrees C; and, e. piercing said patient skin; wherein said step of cooling is eliminating said pain caused to said patient by said step of piercing; further wherein the pain caused by said step of piercing is less than 2 on the SVAS scale.

47. The method according to claim 46, wherein the pain caused by said step of piercing is alleviated by at least one stage of the SVAS scale.

48. The method according to claim 46, additionally comprising step of withdrawing said blood sample and/or said interstitial fluid.

49. The method according to claim 46, additionally comprising steps of introducing said strip-needle into an analyte detector; and, indicating said patient the amount of said analyte.

50. The method according to claim 46, wherein said method additionally comprising step of electrochemically reacting said blood sample and/or said interstitial fluid with said electrochemical sensor.

51. The method according to claim 46, wherein said method additionally comprising step of providing an electrical signal corresponding to said analyte concentration.

52. The method according to claim 46, wherein said method additionally comprising step of converting said electrical signal into a digital value of said analyte concentration.

53. The method according to claim 46, wherein said method additionally comprising step of displaying said digital value to said patient.

54. The method according to claim 46, wherein said method additionally comprising step of applying pressure Pi on said skin prior to and/or during and/or after said step of piercing.

55. The method according to claim 46, wherein said method additionally comprising step of selecting said analyte from a group comprising glucose, uric acid, creatinine, calcium, cholesterol, different proteins and triglycerides.

56. The method according to claim 46, wherein said method additionally comprising step of preventing said temperature T_D from decreasing below 0 degrees C.

57. The method according to claim 46, wherein said method additionally comprising step of controlling said temperature T, said TJ_PCCP, said pressure Pl, said final Tp at said depth D, said ΔT/Δt.

58. The method according to claim 46, wherein said method additionally comprising step of injecting a medicine to said patient.

59. The method according to claim 46, wherein said method additionally comprising step of withdrawing fluids from said patient.

60. The method according to claim 46, wherein said method additionally comprising step of preventing piercing of an undesirable area.

61. The method according to claim 46, additionally comprising steps of (a) storing said analyte concentration; and (b) either online or offline transmitting said concentration to medical personnel.

62. A method for encouraging a self injection compliance of a patient; said method comprising steps of: a. obtaining the hand-held apparatus comprising; i. piercing mechanism adapted to pierce said patient's skin, comprising at least one reciprocating strip-needle; said strip needle is adapted to pierce a region of said skin, and to penetrate to depth D in said skin; said depth D is characterized by an initial temperature T; said strip- needle comprising (a) an actuator adapted to activate said strip-needle; and, (b) an electrochemical sensor adapted to indicate the amount of said analyte; ii. a cooling mechanism adapted to eliminate the pain caused by said piercing to said patient; comprising at least one attachable cooling means, especially a Peltier Cooled Cold Plate (PCCP), in connection with a radiator/thermal mass and DC power supply; said PCCP is characterized by an effective surface area S; said effective surface S is optimized such that said pain caused by said piercing is eliminated; said PCCP is characterized by temperature Tipccp; said PCCP adapted for cooling a portion of said skin prior to and/or during and/or after piercing thereof by said piercing mechanism such that the cooling is obtained at said depth D; said depth D is cooled from said initial temperature T to a final temperature T_D (ΔT) in a period of time t (Δt) by said PCCP; said final temperature TD of said depth D is higher than about 0 and lower than about 13 degrees C; said ΔT/Δt is optimized such that said pain caused to said patient is eliminated; b. lowering said patient's physiology barrier of piercing; and c. piercing said patient; wherein said patient will undergo self injection treatment according to a predetermined medical needs.

63. A method for alleviating needle phobia and/or tension and/or anxiety whilst piercing a patient's skin with an injector, comprising steps of: a. obtaining the hand-held apparatus comprising; i. piercing mechanism adapted to pierce said patient's skin, comprising at least one reciprocating strip-needle; said strip needle is adapted to pierce a region of said skin, and to penetrate to depth D in said skin; said depth D is characterized by an initial temperature T; said strip- needle comprising (a) an actuator adapted to activate said strip-needle; and, (b) an electrochemical sensor adapted to indicate the amount of said analyte; ii. a cooling mechanism adapted to eliminate the pain caused by said piercing to said patient; comprising at least one attachable cooling means, especially a Peltier Cooled Cold Plate (PCCP), in connection with a radiator/thermal mass and DC power supply; said PCCP is characterized by an effective surface area S; said effective surface S is optimized such that said pain caused by said piercing is eliminated; said PCCP is characterized by temperature Tipccp_, said PCCP adapted for cooling a portion of said skin prior to and/or during and/or after piercing thereof by said piercing mechanism such that the cooling is obtained at said depth D; said depth D is cooled from said initial temperature T to a final temperature TQ (ΔT) in a period of time t (Δt) by said PCCP; said final temperature TD of said depth D is higher than about 0 and lower than about 13 degrees C; said ΔT/Δt is optimized such that said pain caused to said patient is eliminated; b. cooling said PCCP to T,PCCP; c. placing said cold PCCP on said skin for a period of time t, such that the cooling is obtained at depth D; d. attuning the temperature at said depth D to final temperature TD at said period of time t; said T_D is higher than about 0 and lower than about 13 degrees C; e. lowering said patient's needle phobia barrier and/or said patient's tension and/or said patient's anxiety; and, f. piercing said patient skin.