Patent Application
20220280728
The present invention relates to medication delivery devices. In particular, the present invention relates to improved systems for measuring a dose delivered from an injection pen, or the like, utilizing a flow sensor within an improved flow channel.
Insulin injection is a required daily task in the lives of people afflicted with diabetes. The action of insulin injection deceptively appears to be a simple task, but it is fraught with a number of risks to the insulin using patient. A patient is routinely requested to maintain a written diary containing the time of the insulin injection and the amount of insulin injected. Maintenance of such a written diary is made difficult by several confounding factors. When an insulin injection is made, the patient may be pre-occupied with another activity such as attending a meeting or participating in a telephone conversation which makes writing an entry into the diary difficult or impossible. Additionally, a consequence of chronic hyperglycemia commonly experienced by people with diabetes is cognitive impairment which renders a patient unable to remember when an insulin dose was taken and/or what dose was actually injected. Accordingly, what is needed is an attachment to an insulin pen which automatically measures the amount of insulin injected and what time the insulin was injected. Such a device solves the inability to make entries into the written diary described above and renders such a written diary as unnecessary or obsolete.
Accurate dose measurement is an important component of any medicine therapy, and especially important for an insulin therapy regimen for diabetics. Recently, a few injection pens and pen attachments have been developed for the purpose of measuring and automatically data logging the dose delivered, e.g. motorized injection pens and attachments that approximate the position of a plunger within an insulin reservoir to determine how much insulin has been delivered. However, none of the current solutions are adequate. Manual recording of insulin doses is inherently inaccurate due to human errors and omissions, and measurement of a plunger, while an improvement over manual recording, is still not accurate enough for individual doses and does not record the time that doses are delivered.
Thermal time of flight (TTOF) sensors have been used to detect the time of flight of a heat pulse induced into moving fluid as it travels through a channel of known cross-section over a known distance in order to measure volumetric flow of the fluid. However, existing TTOF sensors are typically used in steady state flow scenarios, and have not to date been required to measure rapid and large changes in flow rate, as is expected in an insulin injection from an insulin pen, or the like.
An insulin pen attachment has been developed which is an injection molded plastic part into which is placed a chip to measure the flow of insulin out of the insulin pen then into the insulin pen needle and ultimately into the subcutaneous tissue of the insulin using patient. An exemplary insulin pen attachment utilizing a TTOF sensor is described in greater detail in U.S. Pat. No. 10,052,441, the entire contents of which are hereby incorporated by reference. The accuracy of such sensors are dependent on the accuracy of the cross sectional area of the flow channel in which the sensor is housed. Although an injection molded part has its dimensions such as internal diameter and roundness specified, the injection molding process is limited in its ability to achieve precise consistency from one molded part to another. Common production tolerances that can be achieved economically depend on the types of polymer and fillers used can easily exceed +/−0.005″. Finer tolerances approaching +/−0.001″ can be achieved with some polymers, but at a significant incremental cost. Such variability translates into variability in dimensions of the insulin pen attachment to such an extent that each individual attachment would need to be calibrated before insulin pen attachment to ensure accurate measuring performance of the attachment. Individual calibration of each insulin pen attachment is cumbersome and expensive for the manufacturer of such an attachment. Accordingly, there is a need for an improved flow channel to house a flow sensor within an insulin pen attachment, to improve accuracy, lower the need for and costs associated with calibration, and the like.
The above described disadvantages are overcome and other advantages are realized by embodiments of the present invention, as will be appreciated by those of ordinary skill in the art. Exemplary embodiments of the invention provide an improved liquid channel assembly to measure insulin flow as it moves out of an insulin pen and into an insulin pen needle and then ultimately into a patient. Embodiments of the invention replace the plastic assembly formed by injection molding with a metallic cannula or elongated needle. The metallic cannula or needle is provided with a window where a flow measurement chip is positioned. Metallic cannula or elongated needles are advantageously able to be mass produced from welded or seamless tubes from metal sheet. Such processes are advantageously capable of holding tolerances on the inside diameter of less than +/−0.00075″. Consequently, a metallic cannula-based flow channel can be produced at low cost with the sufficient part to part consistency required to eliminate the need for individual calibration of each flow channel assembly. This simplifies the related manufacturing processes.
Additionally, the inner surface of such a metallic-based insulin flow path provides superior consistency of the surfaces presented to insulin flowing through it as compared to the surface of an injected molded part. Such an improved surface finish consistency improves part to part consistency of fluid flow through the flow channel. Fluid flowing through such a channel can either be laminar or turbulent in nature which can affect the quality of the flow sensing measurement capabilities of the flow sensing chip.
Another important attribute of the flow channel is insulin compatibility which can be affected by the surface roughness of the flow channel. Specifically, the fractal length of the flow channel surface can provide sites for nucleation or deposition of the insulin as it transitions through the flow path. A metallic-based flow channel could be electropolished if necessary to present a contact surface with minimal fractal length as compared to an injection molded surface.
The invention will be more readily understood with reference to the embodiments thereof illustrated in the attached drawing figures, in which:
Throughout the drawings, like reference number should be understood to refer to like elements, features and structures.
The exemplary embodiments of the invention will now be described with reference to the attached drawing figures.
As illustrated in
The semi-disposable flow sensor 104 will now be described in further detail in connection with
The durable portion 106 will now be described in further detail with reference to
The manifold 1204 preferably has alignment features that ensure proper orientation and positioning of the semi-disposable portion 104 relative to the durable portion 106 during insertion and set up. A retention feature such as a snap flexure 1208 secures the semi-disposable portion 104 to the durable portion 106 and the insulin pen 102 during use and allows the user to release and remove the semi-disposable when the pen 102 is empty. An electrical connector 118 on the manifold 1204 is preferably oriented in the same direction as the inlet cannula 122 and establishes electrical contact with the durable portion 106 at the same time the flow path is being established when inserting the semi disposable portion 104 into the durable portion 106. The electrical connector 118 shown in
For a given sensing chip with an established heater to sensor spacing, the measurable flow range can be adjusted by changing the flow channel cross section. For a given flow rate, a larger cross section will reduce the apparent velocity observed by the chip, allowing the chip to measure higher flow rates before the sensor signal saturates. The larger cross section will have an inherent trade off of reduced accuracy for low flow rates. A smaller cross section can be paired with a larger element spacing to measure an equivalent flow range with reduced internal volume in the flow path.
The semi-disposable 104, and more specifically the elements comprising the flow channel 1206 are preferably designed with materials that are compatible and non-binding with insulin for the full life of the pen injector, that is, up to at least 28 days. Such materials include ABS plastic and 304 series stainless steel, among others. If liquid silicone rubber is used for the seal between the PCB and the manifold, and since elastomers have tendency to adsorb the preservative from the insulin, the exposed surface of the rubber seal is minimized. Medical grade light cured adhesives are used to bond manifold components. These preferably include flash cured cyanoacrylates or light cured acrylics.
The insulin flow channel 1204 is designed with gradual flow transitions in order to avoid any zones of high shear, which could potentially damage the insulin protein molecules. The manifold threaded hub 114 is preferably designed to accept ISO standard insulin pen needles.
The semi-disposable 104 illustrated in
A method of fabricating a flow sensor for use with an insulin pen will now be described in connection with
Now operation of the dose capture system according to an exemplary embodiment will be described. The dose capture system 100 is installed on an insulin pen 102 as part of the set up sequence with each new pen, that is, every three (3) to seven (7) days (nominally five (5)) for a typical user. The durable portion 106 is first attached to the insulin pen 102. The semi-disposable 104 is then inserted into the distal opening 140 of the durable portion 106. Cannula 122 of the disposable portion 104 pierces the distal septum of the insulin pen 102, creating a flow path over the TTOF sensing element. As the semi-disposable portion 104 is inserted into the durable portion 106, electrical connector 118 is mated with a corresponding electrical connector within the durable portion 106, creating electrical connections to the TTOF sensor 116. A pen needle is threaded onto the distal threaded end 114 if the disposable portion 104, such that the pen needle cannula pierces the septum 112, completing a fluid path from the insulin pen through the flow sensor and pen needle. The combined insulin pen and dose sensing system is then primed in the normal manner to remove trapped air.
Although in this embodiment the assembly sequence is durable portion 106 first and semi-disposable portion 104 second, the system can be designed with the assembly order reversed, as will be appreciated by those of ordinary skill in the art. With this assembly sequence, the durable portion 106 could be used on different insulin pens, such as one pen with slow acting insulin and a second pen with fast acting insulin. The semi-disposable portion 104 preferably attaches to the universal ISO connection found on each insulin pen, and the durable portion 106 would then attach to the semi-disposable portion 104 and to the body of the insulin pen. Since the durable portion 106 does not contact insulin, the durable portion 106 is capable of being swapped back and forth between multiple pens as required for the user's therapy without affecting the sterility of the insulin. For therapy involving more than one insulin or drug, a means of recognizing the additional drug to which the durable attached is provided. For example. a camera on the smart phone that is paired with the durable portion is used to read a bar code on the injection pen when the durable unit is attached to the pen.
The durable portion 106 is preferably paired with the smart phone application, as discussed above. A pairing procedure is preferably done once for a given cell phone 108/durable portion 106 pair. After the initial pairing, the cell phone 108 application preferably automatically recognizes and communication with the paired durable portion 106.
Once installed on the insulin pen, the exemplary system automatically recognizes and captures dose events as part of the user's normal injection sequence. Preferably, no additional use steps beyond those necessary for a normal insulin pen injection are required for the dose sensor after the initial set up on the pen. Dose volumes and times are calculated by the durable portion 106. The durable portion 106 preferably can store many insulin pens worth of dose data. Data recorded by the durable portion 106 is preferably transferred to the smart phone 108 application whenever the smart phone 108 and the durable portion 106 are within broadcast range of one another. The dose data transferred to the smart phone 108 is preferably presented to the user in a convenient and easy to read format. Dose information may also be transferred from the cell phone to other diabetes management devices or to a cloud based data storage site if desired for further processing and analysis and transfer to other stakeholders in the patient's healthcare network.
When the insulin pen 102 is empty, the durable portion 106 is removed and readied for the next use. The spent insulin pen 102 and the semi-disposable portion 104 combination are discarded in the same way as conventional diabetes pens. The durable portion 106 or the semi-disposable portion 104 preferably have features to prevent the reuse of a semi-disposable portion 104 on another insulin pen 102.
Next an exemplary smart phone 108 application will be described. The smart phone application preferably displays dose data to the user in an easy to understand format.
Several aspects of insulin injection present significant challenges to measuring accurate doses. Insulin dose size can vary greatly, from as low as 3.3 microliters to as high as 800 microliters. Dose delivery times can vary from less than 1 second to greater than 10 seconds based upon the size of the dose, diameter and length of the needle being used, the friction and mechanical efficiency of the insulin pen, and actuation force applied by the user or the spring loaded actuation of the pen. A typical insulin injection flow profile 500 is shown in
International standards currently require volumetric accuracy equivalent to the minimum resolution of the insulin pen or +/−5% of the dose volume, whichever is greater. For example, on the typical U-100 pen with a dial resolution of 1 U, accuracy of +/−10 microliters for doses less than 200 microliters and +/−5% for doses greater than 200 microliters is required. Higher insulin concentrations scale inversely with respect to volume. For instance, a U200 insulin pen with resolution of 1 U would require volumetric accuracy of +/−5 microliters for doses less than 100 microliters and +/−2.5% for doses greater than 100 microliters.
Small diameter needles are typically used for insulin injections which can create relatively high back pressures. Accordingly, a flow sensor according to an embodiment of the invention must be able to tolerate back pressures of up to 1 mega-pascal.
Since the flow sensor is in the insulin delivery path, it must be manufactured from materials that are chemically compatible with the insulin, and must not in any way react with or break down the insulin.
According to exemplary embodiments of the invention, TTOF flow sensing uses a central heating element with offset thermal sensing elements. The offset of each sensing element is preferably, but not necessarily, symmetrical on either side of the heating element. A time varying signal of known amplitude, frequency, shape and phase is applied to the central heater. The heat signal diffuses through the fluid toward the sensors, where it is detected with both reduced amplitude and a shifted phase relative to the drive signal. The amplitude signal corresponds to calorimetric sensing while the phase shift signal corresponds to time of flight sensing. Without flow, the thermal conduction zone around the heater is symmetric, as shown in
Several dose tracking insulin pens are currently available on the market. These pens track and monitor the motion of the pen mechanism to determine the dose delivered. Conventional pens use a small display to communicate intended dose volume of recent injections. Some newer models also incorporate wireless communication to a smart phone. Tracking the pen injection mechanism can fail to correctly monitor dose received by the user, as the pen mechanization has inherent error, which can be additive to the error in the sensing apparatus. Additionally, user errors, such as withdrawing the pen from the injection site before the dose is completely delivered into the tissue or not recognizing failures with system components, e.g. a pinched or clogged pen needle, can all contribute to not delivering the intended dose. Unlike conventional insulin pens, exemplary embodiments of the invention advantageously utilize TTOF sensing to measure the time and changing insulin flowrate profile actually delivered from the pen, allowing for more complete and accurate information on the actual dose delivered.
TTOF sensors measure the velocity of fluid passing the sensor. Accordingly, the volume of fluid passing through a flow sensor utilizing TTOF to measure fluid velocity is dependent upon the cross sectional area of the flow channel through which the fluid flows. As discussed above, injection molded parts are limited in how accurate the flow channel geometry can be made, and in how variable they are from part to part. Embodiments of the present invention improve upon the above described disposable portion that interfaces between the insulin pen and a pen needle to measure flow from the insulin pen, through the disposable portion, and into the pen needle to the patient. Metal tubes can be manufactured relatively inexpensively, and with highly accurate inner diameters, such as is known for needles and metal cannulas. Embodiments of the present invention advantageously utilize a metal cannula as the flow channel through which fluid flows for flow rate measurement and dose recording.
Exemplary embodiments of the invention form the sensor onto a glass substrate. The glass substrate has low thermal conductivity and structural rigidity to prevent deformation of the sensor during a dosing event. Forming the sensor surface on a glass substrate is preferred in the liquid medicament flow application, since preferably one sensor surface is exposed to the medicament within a flow channel, and overcomes the limitations described above in connection with thin membrane or bridge structures used on gaseous applications where pressures imparted onto the sensor are not a concern.
In another exemplary embodiment of the invention, multiple sensor chips are used in tandem to increase the dynamic range of the sensor.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US2020/043254 | 7/23/2020 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 62878382 | Jul 2019 | US |
