Patent Application
20190110725
The present invention relates to a method and its associated apparatus for autonomous minimally-invasive capillary blood extraction comprising a miniature in-plane lancing device for the purpose of lancing the skin and extracting a whole blood sample from capillaries below the surface of the skin.
Blood extraction is an important medical practice. Blood samples extracted from patients can be sent to laboratories for tests which can determine physiological states, diseases and drug effectiveness. If a blood test requires only a tiny amount of blood, blood extraction can be performed by patients themselves at home using miniature devices. For example, Diabetes mellitus is a systemic disorder that results in elevated blood glucose levels due to insulin deficiency in the body and subsequently leads to many secondary complications (American Diabetes Association, 2012). Diabetes mellitus requires long-term treatment, the goal of which is to achieve optimal glucose monitoring and control with the long-term aim of decreasing the risk of vascular complications while minimizing daily glycemic variations (Hendriks, Brokken, Oomens, Baaijens, & Horsten, 2000). Current standards for blood glucose monitoring for diabetics rely on finger-prick testing performed by patients at home using a device manually operated by themselves (Penfornis, Personeni, & Borot, 2011). Though accurate in detecting blood glucose levels, finger-prick testing is painful and inconvenient. In a recent systematic review of clinical trials, it has been found that providing a distraction can reduce the acute pain felt by children and adolescents during needle-related procedures (Uman, Chambers, McGrath, & Kisely, 2008). Therefore, users would feel less procedural pain if they were distracted by their ordinary daily activities. There is an obvious need for wearable blood extraction devices which would be pre-programmed to automatically obtain static blood samples multiple times over a long period of time with minimal pain and limited user intervention.
Standard diabetic monitoring relies on finger-prick testing by a miniature device (Penfornis, Personeni, & Borot, 2011). Though highly accurate in detecting blood glucose levels, finger-prick testing is painful and inconvenient. Therefore, patients, especially those in their youth and in active maturity, are often unable to adhere to the test schedule. As a result, irregular measurements limit the applicability of the finger-prick test and disturb the management of diabetes (Penfornis, Personeni, & Borot, 2011).
Continuous glucose monitoring (CGM), introduced in 1960s, is a concept which measures glucose levels in the interstitial fluid (ISF). A CGM device can be subcutaneously inserted and records ISF glucose level but only for 3-7 days (Penfornis, Personeni, & Borot, 2011). Clinicians rely on CGM to retrospectively understand glucose level trends within this short period and guide diabetes management (Oliver, Toumazou, Cass, & Johnston, 2009). Its accuracy is dependent on the equilibrium of glucose levels between ISF and blood. The balance between the two glucose levels further accounts for a time delay in the measurement (Penfornis, Personeni, & Borot, 2011) and requires frequent recalibration using finger-prick testing (Hoeks, Greven, & Valk, 2011).
There is an obvious need for wearable semi-invasive blood sampling devices which would be able to automatically obtain and analyze a series of static blood samples over an extended period of time with minimal pain and limited user intervention. This can be achieved by inserting a hypodermic needle to a level where capillaries are abundant but nerve endings are rare (Gattiker, Kaler, & Mintchev, 2005).
On average the skin of an adult has a thickness of roughly 2 mm (Martini, 2001). The outermost layer of the skin is the stratum corneum which is a thin but very dense and resistive compound of dead cells. The thickness of stratum corneum varies among different skin sites, ranging from 23.6±4.33 μm for the forearm and 173.0±36.96 μm for the palm (El-Laboudi, Oliver, Cass, & Johnston, 2013). Situated below is the epidermis which protects against the rays of the sun and has a thickness of 30 to 130 μm. The dermis, which is located under the epidermis and ranges 800-1500 μm in thickness, holds abundant blood vessels, hair follicles, sweat glands and few nerve endings (Hendriks, Brokken, Oomens, Baaijens, & Horsten, 2000). Lastly, the subcutaneous tissue is a fatty layer located below the dermis which connects to internal organs. It is usually about 1.2 mm deep (Hendriks, Brokken, Oomens, Baaijens, & Horsten, 2000). In order to successfully acquire blood sample, a lancet has to penetrate the resistive stratum corneum and reach the dermis layer which contains capillaries.
Prior methods of acquiring a blood sample suffer from the need for human intervention in order to control the lancing device. Kuhr and Forster U.S. Pat. No. 6,419,661 describe a lancing device for withdrawing blood for diagnostic purposes, which has been implemented in the Accu-chek blood glucose monitoring products by Roche. In this patent, a lancet holder for holding a lancet and a lancet drive having a loadable elastic drive spring are provided within an elongated housing. The triggering of the spring is performed by finger-pressing on a button. This device exemplifies the devices used in a standard finger-pricking test that require two separate components: a lancing device to perform the lancing as the first step and a blood testing device to load the blood sample as the second step. As described above, finger-prick testing suffers from low patient compliance due to painful experiences and inconveniences caused. Furthermore, time delays between these two steps may potentially contaminate blood samples and result in inaccurate tests.
Perez and Roe U.S. Pat. No. 8,257,276 describes a blood sampling assembly with a single spring-force triggered lancet and an integrated capillary-action based blood collection mechanism which can be directly associated with a blood testing device. This device is a convenient single disposable unit. Patients need to take only one action to get their blood glucose level reading. Other similar patents include Haynes U.S. Pat. No. 4,920,977 and Jordan et al., U.S. Pat. No. 4,850,973.
An automatic blood collection system comprising a plurality of lancets is also disclosed in Kelly, U.S. Pat. No. 6,530,892. A drive unit is implemented by a magnet, similarly to the above mentioned prior art. However, these types of integrated devices still require hand control and therefore the associated problems described before are still not overcome.
The difficulty of implementing a fully automated and wearable blood sampling and analysis device lies in the device miniaturization, and in particular, the actuator miniaturization. Maximal stroke and optimal insertion force are the two primary design factors for a lancing device for blood sampling. In order to penetrate the skin surface, the minimum lancing force required is approximately 30 gf (Tsuchiya, Nakanishi, Uetsuji, & Nakamachi, 2005). On the other hand, the actuator must be capable of moving the lancet to depths between 0.5 to 1.4 mm below the skin, where capillary vessels are abundant in order to successfully acquire blood samples. For manual lancing devices, a wide range of large actuators that can achieve these two requirements can be selected as there is relatively less restriction for the actuator size.
In order to provide sufficient lancing force and stroke for wearable blood sampling devices, other actuation methods have been proposed. Kaler et al. US Pat. App. No. 20050228313 proposed a miniature scale system that automatically penetrates the skin to extract a static blood sample for on-site analysis.
Sof-Tact™ is a fully integrated blood glucose testing device. The device features a lancet holder and a strip holder, which house a lancet and a test strip inside the device's cover. To perform a blood glucose test, users load a test strip and a lancet inside the device and then gently press the gasket on the forearm or other sites. Once a user presses the main button, the Sof-Tact™ electrical actuator automatically lances the skin, draws a blood sample using suction, transfers the sample to the embedded test strip and provides a glucose reading in 20 seconds.
The POGO™ System by Intuity Medical, Inc. (see http://www.presspogo.com/pogo/system/) is a commercially available blood glucose monitoring device that is designed to reduce the steps and components required for a finger-pricking test. The POGO™ System has an integrated cartridge which consists of multiple pairs of miniaturized lancet and test strip. The user presses a finger on the button of this device to trigger a skin-lancing mechanism below that button that pokes the fingertip and withdraws a blood sample, which is immediately wicked into a miniaturized strip to get a reading. At the end of each lancing, the cartridge revolves and reloads a new lancet and its associated strip for the next test.
It remains technically challenging to implement a fully automatic BGM device that can be wearable at the fingertips. As another point of view, such a device may not be accepted by the market as it is quite visible to others and will also affect users' hand activities. Furthermore, the fingertips are also abundant with nerve endings and are therefore sensitive to skin lancing. Automated skin lancing at the fingertips is expected to cause the same level of pain compared to manual fingerpricking, which could become a concern to potential users in the future. These semi-automated devices reduce errors due to mishandling related to the fingerpricking test. In spite of their advantages, semi-automated BGM devices are still bulky in size due to their mechanical design. Both Sof-Tact™ and Pogo™ are about the size of a cellphone and designed as handheld devices that require strong manual force input to trigger their skin lancing mechanisms. Therefore, they are not suitable for miniaturization towards a wearable device. The present invention provides a method and apparatus for using the forces exerted during normal mammalian movements to autonomously actuate a lancet to pierce the skin of the mammal which is integrated into a wearable autonomous device for ultimate convenience.
The objective of the present invention is to disclose a method and its associated apparatus for minimally-invasive skin penetration comprising a miniature in-plane lancing device for the purpose of lancing the skin and extracting whole blood sample from capillaries below the surface of the skin.
The present invention aims to be integrated with a wearable blood sampling device so that blood sampling can be done without any human intervention.
A method and its associated apparatus for minimally-invasive skin penetration and whole blood extraction is described. The proposed method may be implemented on a wearable blood sampling device which would be pre-programmed to automatically extract static blood samples multiple times over a prolonged period of time with minimal pain and limited user intervention. Whole blood samples collected using the present invention can be automatically analyzed on site for monitoring certain blood components.
According to one aspect of the invention, there is provided a system for fluid sampling and analysis from a biological body, whether human or otherwise, using the own natural motions of the said body, said system comprising an integrated unit that comprises: (a) a lancing assembly, (b) an actuator operable to drive movement of said lancing assembly into piercing relation to the biological body at a lancing site thereon, (c) a sample interface holder configured to support a sample interface in a position receiving a fluid sample from the lancing site, and (d) circuitry connected to the sample interface holder to enable sample analysis.
In detailed embodiments, the proposed apparatus consists of rotational and translational actuator components which work together to convert the forces exerted by normal mammalian movement into the power needed to penetrate the skin with a lancet either directly or indirectly through the use of further mechanisms to promote consistency of penetrations. One embodiment further comprises an electrically-controlled mechanical locking mechanism that initially blocks the movements of the rotational and translational actuator components. Further description of the present preferred embodiment of the apparatus is illustrated in the appended drawings.
According to another aspect of the invention, there is provided a method of obtaining a fluid sample from a biological body, whether human or otherwise, said method comprising using natural movement of said biological body to trigger a lancing action releasing a fluidic sample from said biological body.
For the purposes of promoting an understanding of the principles of this invention, reference will now be made to the embodiments illustrated in the figures and the specific terminology will be used to describe these embodiments. It will be nonetheless understood that no limitation is intended.
The present invention provides a method and its associated apparatus for lancing the skin for the purpose of obtaining and analyzing a whole blood sample. In its preferred embodiment, the invention combines a set of rotational and translational actuation components integrated with a spring-loaded safety lancet as well as an electrically-controlled mechanical locking mechanism that controls the freedom of movement of the set of rotational and translational actuation components. The actuation components are capable of transforming a force exerted on the rotational element into translational movement of the lancet assembly approximately orthogonal to the intended skin's surface. This integrated unit is useful in combination with other devices which preform complementary functions such as collecting, analyzing or testing the blood.
In contrast to the prior art, the present invention introduces an actuator capable of converting the forces exerted by natural mammalian movements, such as, but not limited to, walking, into horizontal translation of the lancet assembly driven by the rotational element. The developed actuation system can (a) harness the energy produced by natural mammalian movements to automatically trigger the skin lancing system; and (b) apply an oscillating pressure to the body to accelerate blood flow from capillary vessels to the skin surface via the wound created by lancing the skin. The proposed actuation method reduces and even eliminates the significant difficulties associated with housing the components of a wearable blood sampling device due to typical space and energy constraints.
In the preferred embodiment illustrated in
The body 101 can be fabricated from a biocompatible hard plastic or metal. The body 101 acts as the framework in which all other components of the actuator are housed and/or are coupled to. The body 101 also features a guiding channel 114 which will be discussed in further details hereafter.
The rotational element 102 can be fabricated from any biocompatible hard plastic or metal. The rotational element has a first lever-like member 102a situated internally of the body 101 and pivotally coupled to the body via pin 103 so that the rotational element 102 has freedom of rotation about the longitudinal axis of pin 103. A second saddle-like member 102b of the rotational element is affixed to and stands upward from the first lever-like member 102a on a side of the pin 103 opposite the return spring 105, and protrudes externally of the body and embraces over the slide element 106 and the spring-loaded lancet assembly 107 carried thereby. The second member 102b of the rotational element engages with the sliding element 106 via a pair of slot joints on opposite sides of the sliding element 106. One of these slot joints can be seen at 109 in
The locking mechanism 104 can be implemented using a solenoid as illustrated, but this is not meant to be a limiting method for restricting the movement of rotational element 102. The locking mechanism is responsible for the initial prevention of the movement of the rotational and translational components (i.e. rotational element 102 and slide element 106) of the actuator. It is released in order to initiate the actuation process as described hereafter. The locking mechanism 104 can thus be controlled electronically using an onboard microcontroller of the unit 100 to allow for autonomous actuation. As shown in
The return spring 105 can be fabricated from metal or plastic as known in the art. The purpose of the return spring 105 is to provide a force which opposes the effects of gravity on the rotational element 102 so that the device is oriented in the initial default position illustrated in
The sliding element 106 can be fabricated from any biocompatible hard plastic or metal. The purpose of the sliding element 106 is to hold the spring-loaded lancet assembly 107, and to move the spring-loaded lancet assembly 107 towards a user's toe in the longitudinal direction along a horizontal plane as the result of a force exerted on the rotational element 102 by said user's toe. As described before, the sliding element 106 is coupled with the rotational element 102 via the sliding-pin joints 109. The sliding element 106 also has a dove tail which is coupled with the guiding channel 114 of the body 101 to restrict the movement of the sliding element 106 generated by the translation of the torque on the rotational element 102 to linear translational displacement along a horizontal plane approximately orthogonal to the skin at the tip of the user's toe.
The lancet assembly 107 can be fabricated from any biocompatible material such as stainless steel, titanium, as well as many other suitable materials known in the art. In the preferred embodiment, the lancet of the assembly is driven by a spring 115, but this is not meant to be limiting. This spring is pre-loaded (compressed) and is released by depression of a button 111, as known in the art. The reason the preferred embodiment utilizes a spring-loaded lancet is to promote consistency in actuation parameters. Preferably, the lancet 107 is sufficiently sharpened to make an incision through the skin surface and reach the underlying capillary vessels in order to extract sufficient volumes of blood. In the illustrated embodiment, the spring-loaded lancet is shown to be a separate disposable entity however this is not meant to be considered limiting.
Now referring to
Now referring to
The actuator is engaged by removing the locking mechanism 104 from its locked state with the rotational element. This is accomplished by supplying adequate power to the push-pull solenoid under the control of the onboard microcontroller, which also carried on the body of the integrated unit along with a battery for powering the microcontroller and locking mechanism solenoid. When the solenoid is activated by the micro-controller, the solenoid plunger retracts into an unlocked state disengaged from the rotational element 102, at which point the rotational element 102 is allowed to rotate freely about the longitudinal axis of pin 103. When a force is exerted on the proximal end of the rotational element, torque is generated on the rotational element 102. The force on the proximal end of the rotational element is supplied by typical mammalian movement such as walking, however this is not meant to be considered limiting. The torque on the rotational element 102 results in clockwise angular displacement of approximately 30 degrees of the rotational element 102. This angular displacement of, and torque on, the rotational element 102 is converted to horizontal translation of, and force exerted on, the sliding element 106. The horizontal translation of the sliding element 106 results in depression of the pressure-activated push button 111 of the spring-loaded lancet 107 as it comes into contact with the intended lancing site on the skin of the user's toe. Depression of the push button 111 triggers the compressed spring 115 to be released, causing the lancet 107 to penetrate the skin with a predetermined force, incision size, and incision depth. The result of these motions is that the actuator is oriented in the position shown in
The actuator is returned to is starting orientation shown in
The subsequent oscillating exertion of force on the proximal end of the rotational element 116 causes an oscillating pressure within the capillary tissue of the mammal which forces blood to be expelled from the created incision. This blood is then collected by the test strip 108, whose blood sample interface opening is positioned in close proximity to the lancing site to enable this automatic collection of the sample. The blood sample can then be analyzed using methods known in the arts for detecting the presence of concentration of specific molecules such as, which is not meant to be limiting, blood glucose molecules.
In summary, none of the test strip arrangements presented herein are meant to be limiting but rather to provide an insight into the methods which can deliver reliable test results.
| Number | Date | Country | |
|---|---|---|---|
| 62574062 | Oct 2017 | US |
