Improved flow path for flow measurement

Abstract

An improved flow sensor is provided that allows for accurate dosage measurements with little or no sensor calibration due to a highly accurate flow channel cross section. The flow channel is formed as a metal tube. A sensor window is formed in a sidewall of the metal tube, and a flow sensor is mounted within the sensor window. A flow manifold is formed around the metal flow channel.

Description

[Technical Field]

[0001] The present invention relates to medication delivery devices, and in particular to an improved system for measuring the dose delivered from an injection pen or the like, utilizing an improved in-flow path flow sensor. [Background technology]

[0002] Insulin injections are a necessary daily routine in the lives of people with diabetes. While the act of insulin injection appears to be a simple task, it carries many risks for patients who use insulin. Patients are routinely required to keep a diary that includes the time of insulin injection and the amount of insulin injected. Maintaining such a written diary is made difficult by several confounding factors. When an insulin injection is administered, the patient may be preoccupied with another activity, such as attending a meeting or participating in a telephone conversation, which makes it difficult or impossible to complete the diary. Furthermore, a common consequence of chronic hyperglycemia experienced by people with diabetes is cognitive impairment, which makes it impossible for patients to remember when an insulin dose was administered and / or which dose was actually injected. Therefore, what is needed is an attachment mechanism to an insulin pen that automatically measures the amount of insulin injected and the time the insulin was injected. Such a device would address the impossibility of completing the written diary described above, making such diary entry unnecessary or obsolete.

[0003] Accurate dose measurement is a critical component of any drug therapy and is particularly important for insulin therapy regimens for diabetic patients. Recently, several injection pens and pen mounting mechanisms have been developed for the purpose of measuring delivered doses and automatically data logging them, for example, powered injection pens and mounting mechanisms 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 sufficient. Manual recording of insulin doses is inherently inaccurate due to human error and negligence, and plunger measurement, while an improvement over manual recording, is still not sufficiently accurate for individual doses and does not record the time that a dose was delivered.

[0004] Thermal time-of-flight (TTOF) sensors are used to detect the time of flight of a heat pulse induced in a moving fluid as the fluid travels through a flow path of known cross-section over a known distance in order to measure the volumetric flow rate of the fluid. However, existing TTOF sensors are generally used in steady-state flow scenarios and have not until now been required to measure rapid, large changes in flow rate, such as those expected during insulin injection from an insulin pen.

[0005] Insulin pen attachment mechanisms have been developed, which are injection-molded plastic parts into which a tip is placed to measure the flow of insulin as it exits the insulin pen, enters the insulin pen needle, and ultimately enters the subcutaneous tissue of the patient using the insulin. An exemplary insulin pen attachment mechanism utilizing a TTOF sensor is described in detail in U.S. Patent No. 6,277,949, the entire contents of which are incorporated herein by reference. The accuracy of such sensors depends on the precision of the cross-sectional area of ​​the flow channel in which the sensor is housed. While injection-molded parts have specified dimensions such as inner diameter and roundness, the injection molding process is limited in its ability to achieve precise uniformity from one molded part to another. Typical manufacturing tolerances that are economically achievable depend on the type of polymer and filler used and can easily exceed + / - 0.005 inches. With some polymers, finer tolerances approaching + / - 0.005 inches can be achieved, but at significantly increased cost. Such variations lead to dimensional variations in insulin pen mounting mechanisms to the extent that each individual mounting mechanism must be calibrated before being used to ensure accurate measurement performance of the insulin pen mounting mechanism. Individual calibration of each insulin pen mounting mechanism is cumbersome and expensive for manufacturers of such mounting mechanisms. Therefore, there is a need for an improved flow path, such as one that accommodates a flow sensor within the insulin pen mounting mechanism, improving accuracy and reducing the need for and costs associated with calibration. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] U.S. Patent No. 10,052,441 Summary of the Invention

[0007] As will be appreciated by those skilled in the art, embodiments of the present invention overcome the above-mentioned drawbacks and achieve other advantages. Exemplary embodiments of the present invention provide an improved fluid channel assembly for measuring insulin flow as it exits an insulin pen, enters an insulin pen needle, and then ultimately enters a patient. In embodiments of the present invention, a plastic assembly formed by injection molding is replaced with a metal cannula or elongated metal needle. The metal cannula or metal needle is provided with a window in which a flow measurement tip is positioned. The metal cannula or elongated metal needle can be advantageously mass-produced from welded or seamless tubing from sheet metal. Such a process can advantageously hold an inner diameter tolerance of less than + / - 0.00075 inches. As a result, metal cannula-based flow channels can be manufactured at low cost with sufficient part-to-part uniformity required to eliminate the need for individual calibration of each flow channel assembly, thereby simplifying the associated manufacturing process.

[0008] Furthermore, the interior surfaces of such metal-based insulin channels provide superior uniformity of the surface presented to insulin flowing therethrough compared to the surfaces of injection-molded parts. Such improved surface finish uniformity improves part-to-part uniformity of fluid flow through the channels. Fluid flow through such channels can be either laminar or turbulent in nature, which can affect the quality of the flow sensing measurement capabilities of the flow sensing chip.

[0009] 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 insulin nucleation or deposition as insulin migrates through the flow channel. Metal-based flow channels can be electropolished if necessary to provide a contact surface with minimal fractal length compared to injection-molded surfaces. [Brief explanation of the drawings]

[0010] The present invention will be more readily understood by reference to the embodiments thereof illustrated in the accompanying drawings. [Figure 1] FIG. 1 illustrates a dose capture system according to an exemplary embodiment of the present invention. [Figure 2] FIG. 2 shows a semi-disposable portion of the dose measuring system of FIG. 1. [Figure 3] FIG. 2 shows a durable part of the dose capture system of FIG. 1. [Figure 4] FIG. 1 is a block diagram of a dose capture system, according to an exemplary embodiment of the present invention. [Figure 5] 1 is a cross-sectional view of a semi-disposable portion of a dosage measuring system utilizing an improved flow path according to an exemplary embodiment of the present invention. [Figure 6] 1A and 1B are front and perspective views of an improved flow path according to an exemplary embodiment of the present invention; [Figure 7] 1 is a flowchart illustrating a method of forming a semi-disposable portion of a dosage measurement system, according to an exemplary embodiment of the present invention. [Figure 8A] 10A-10C illustrate exemplary user interfaces of a dose capture system, according to exemplary embodiments of the present invention. [Figure 8B] 10A-10C illustrate exemplary user interfaces of a dose capture system, according to exemplary embodiments of the present invention. [Figure 8C] 10A-10C illustrate exemplary user interfaces of a dose capture system, according to exemplary embodiments of the present invention. [Figure 9] FIG. 10 illustrates a dose profile captured by a dose capture system, according to an exemplary embodiment of the present invention. [Figure 10] FIG. 1 shows a cross section of the static temperature field in a sensor with no fluid flow. [Figure 11] FIG. 1 shows a cross section of a distorted temperature field in a sensor with a flowing fluid. [Figure 12]FIG. 10 illustrates a trapezoidal summation method for integrating flow readings to calculate dose volume, according to an exemplary embodiment of the present invention. [Figure 13] FIG. 10 illustrates an alternative embodiment of the present invention utilizing two flow sensors to improve the dynamic range of the dose capture system, according to an exemplary embodiment of the present invention.

[0011] It should be understood that throughout the drawings, like reference numerals refer to like elements, features and structures. DETAILED DESCRIPTION OF THE INVENTION

[0012] Exemplary embodiments of the present invention will now be described with reference to the accompanying drawings. FIG. 1 illustrates an exemplary dose capture system 100, preferably integrating with a conventional insulin pen 102. While this exemplary embodiment is shown with respect to an insulin pen, it should be appreciated that embodiments of the present invention may be utilized with any suitable medication device, including, but not limited to, a patch pump, an intravenous pump, a fixed dose injector, an auto-injector, a syringe, and the like. The system 100 includes a semi-disposable flow sensor 104 that includes a fluid manifold and a thermal time-of-flight (TTOF) hybrid sensor. The semi-disposable flow sensor 104 preferably has a lifespan comparable to that of the insulin pen 102 to which it is attached. The system 100 further includes a durable portion 106, which preferably has a multi-year lifespan. The durable portion 106 consists of a plastic enclosure containing electronic circuitry to power the flow sensor and read the sensor signal, a microprocessor for analyzing dosage data, a rechargeable battery, temperature and motion and / or position sensors, and wireless communication circuitry. The durable portion 106 also preferably has a removable cap 146 that can provide one or more of the following functions: protecting the semi-disposable flow sensor, shielding the insulin from light, protecting the patient from unintentional needlesticks, and acting as a switch for an electrical contact closure that activates and deactivates the sensing system when the cap 146 is removed from or replaced on the durable portion, respectively. The durable portion 106 is preferably adapted to be charged via a standard connector, such as a USB port, or, preferably, via a wireless charging system. Preferably, a smartphone 108-based software application wirelessly interacts with the durable portion 106 to read, store, and present dosage information. The application can also interact with other electronic devices and networks, such as glucose meters, activity and fitness meters, or diabetes care networks. A software application is preferably paired with durable portion 106 only once.After the initial pairing, the software can automatically recognize the durable portion 106 and automatically transfer data reliably from the durable portion 106 to the smartphone application. It should be appreciated that in alternative embodiments of the present invention, other pairing configurations may be implemented as appropriate and desired.

[0013] 2, the semi-disposable flow sensor 104 preferably has a threaded portion 114 for accepting a standard insulin pen needle 110. The pen needle 110 is preferably changed conventionally with each insulin dose.

[0014] The semi-disposable flow sensor 104 will be described in further detail with respect to FIG. 2 . As shown, the distal end of the semi-disposable flow sensor 104 includes a septum 112 and a universal pen needle thread 114. A MEMS flow sensor chip 116 is mounted on a carrier printed circuit board and secured to the semi-disposable flow sensor assembly 104. An electrical connector 118 is provided for making an electrical connection between the semi-disposable flow sensor portion 104 and the durable portion 106. The proximal end of the semi-disposable flow sensor portion 104 includes an insulin pen connection 120 with an inlet cannula 122. The semi-disposable object 104 also preferably includes alignment features 124 on the housing for aligning the semi-disposable object 104 within the durable portion 106. The semi-disposable object preferably includes an axial lock 126 or similar feature for releasably locking the semi-disposable object 104 within the durable portion 106. As shown, the shaft lock 126 includes a flexible member 128 and a locking member 130 adapted to be locked to a corresponding feature on the durable portion 106 .

[0015] The durable portion 106 will now be described in further detail with reference to FIGS. 3 and 4. As shown, the durable portion 106 includes an outer housing 132 that preferably includes an opening for a charging port 134. The charging port 134 preferably conforms to a commonly adopted standard, such as mini-USB, although any suitable connection, including a proprietary connection, may be utilized. Alternatively, a wireless charging configuration can be incorporated into the durable unit. The durable unit has a proximal end 136 that includes an opening 138 for an attachment mechanism to the insulin pen 102. The durable unit further has a distal end 140 that includes an opening 142 adapted to receive the semi-disposable portion 104. The durable portion 106 is preferably contoured to receive a removable cap 146 and includes a detent 144 or similar feature to do so. The durable portion 106 includes a printed circuit board 2000, shown in FIG. 4. Durable PCB 2000 preferably includes an ASIC 2002 that provides an analog filter 2004, a lock-in / instrumentation amplifier 2006, and an oscillator 2008. The ASIC 2002 provides data to an analog-to-digital converter (ADC) 2010. The ADC 2010 then provides data to a Bluetooth® ARM processor 2012. Durable PCB 2000 further includes a communications port 2014, such as a micro USB port, an interface / sensor 2016, and battery components 2018 / 2020. Durable PCB 2000 interfaces with a MEMS chip 2022 that provides a heater 2024 and a sensor element 2026.

[0016] FIG. 5 is a cross-sectional view of a semi-disposable flow sensor 104. It shows a sensor chip 1200 mounted on a PCB 1202 with the sensor surface exposed within a flow manifold 1204. A metal cannula 1301 is formed inside the flow manifold 1204. The metal cannula can be formed with a more precise geometry, including the inner diameter, improving the overall accuracy of the sensor. Metal cannulae or elongated metallic needles can be advantageously mass-produced from welded or seamless tubes from sheet metal. These tubes are then thinned through the use of several intervening annealing and drawing steps until the final dimensions are achieved. Advantageously, calibration of sensors so formed can be simplified or eliminated, since sensor-to-sensor variability is reduced. The chip 1200 can be attached and sealed to the manifold 1204 by any suitable means, including UV-curable adhesive, molded-in elastomeric seals, or overmolded elastomeric seals. One end of the manifold 1204 contains the needle cannula 122 and attaches to the ISO-standard hub of the insulin pen. It should be understood that the needle cannula 122 need not be a separate component from the metal cannula 1301 but may be integrally formed therewith. Attaching the manifold 1204 to the pen 102 punctures the rubber septum on the insulin cartridge, establishing an insulin flow path across the sensor 1200. The opposite end of the manifold 1204 contains threads and an elastomeric septum that create an ISO-compliant connection for the insulin pen needle. The manifold 1204 is formed to have a minimum residual (non-recoverable) internal volume, ideally less than 30 microliters, and a minimum additional length, ideally less than 25 mm. The manifold 1204 includes a metal flow path 1206 designed with a cross-sectional area and smooth transitions that ensure laminar flow is maintained across the face of the sensor 1200 at all times. The face of the sensor 1200 is specifically positioned relative to the channel wall so that it is always in the shear zone of the insulin flow. The placement of the sensor face should be 0 to 0.1 mm protruding from the manifold wall, with 0.05 mm being preferred.A metal flow channel 1206 through manifold 1204 is preferably formed in a substantially straight line from inlet cannula 122 to sensor surface 1200 toward the end of the pen needle to promote laminar flow of insulin through flow channel 1206.

[0017] The manifold 1204 preferably has alignment features that ensure proper orientation and placement of the semi-disposable portion 104 relative to the durable portion 106 during insertion and setup. Retention features, such as snap flexes 1208, secure the semi-disposable portion 104 to the durable portion 106 and insulin pen 102 during use and allow the user to open and remove the semi-disposable portion when the pen 102 is empty. The 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 that a fluid path is established upon insertion of the semi-disposable portion 104 into the durable portion 106. While the electrical connector 118 shown in FIG. 5 has conductive pins, other features, such as conductive pads, flexible cables, conductive flexures, or pins, could also be used.

[0018] For a given sensing tip with a given heater to sensory space, the range of measurable flows can be adjusted by changing the channel cross-section. At a given flow rate, a larger cross-section will reduce the apparent velocity observed by the tip, allowing the tip to measure higher flow rates before the sensor signal saturates. A larger cross-section has an inherent trade-off of reduced accuracy at low flow rates. A smaller cross-section, combined with a larger element space, can be used to measure an equivalent range of flows with a reduced internal volume in the channel.

[0019] The semi-disposable item 104, and more particularly the components comprising the flow path 1206, are preferably designed with materials that are compatible with and will not bond to insulin for the entire life of the pen injector, i.e., up to at least 28 days. Such materials include ABS plastic and 304 series stainless steel, among others. When liquid silicone rubber is used for the seal between the PCB and manifold, and because elastomers tend to adsorb preservatives from insulin, the exposed surface of the rubber seal is minimized. Medical-grade light-cure adhesives are used to bond the manifold components. These preferably include flash-cure cyanoacrylates or light-cure acrylics.

[0020] The insulin flow path 1204 is designed with a gradual flow transition to avoid any zones of high shear that could potentially damage the insulin protein molecules. The manifold threaded hub 114 is preferably designed to accept an ISO standard insulin pen needle.

[0021] The semi-disposable object 104 shown in FIG. 4 is preferably an injection-molded thermoplastic part formed around a metal cannula 1301. FIG. 6 shows an exemplary embodiment of the metal cannula 1301, including both a puncture portion 1302 and a flow path portion 1303. As shown, a sensor window 1304 is formed within the flow path portion 1303. A flow sensor is disposed within the sensor window 1304 to access the fluid flowing through the flow path. The flow path portion 1204 of the semi-disposable object 104 can be replaced with micro-machined metal, plastic, ceramic, or composite tubing 1301 to provide the smooth flow transitions described above. However, for accuracy, the portion of the flow path where the sensor window 1304 is located is preferably formed from the metal cannula. The metal flow path 1206 is preferably insert molded into the semi-disposable object 104, or the plastic portion of the semi-disposable object 104 is injection molded around the metal flow path.

[0022] A method of manufacturing a flow sensor for use with an insulin pen is described with reference to FIG. 7. In step 701, a metal flow channel is formed having a predetermined cross-sectional area. Needle manufacturing techniques are preferably used, taking advantage of high-precision diameters. The proximal end of the metal flow channel optionally includes a puncture member. In step 702, a sensor window is formed between the ends of the metal flow channel. In step 703, a flow manifold body is injection molded around the metal flow channel. The flow manifold body includes a proximal end adapted to expose the puncture member and shaped to connect to an insulin pen. The flow manifold distal end includes a threaded outer portion adapted to receive a pen needle and is shaped to receive a septum therein. In step 704, a flow sensor is attached to the window in the flow channel.

[0023] The operation of the dose capture system according to an exemplary embodiment will now be described. The dose capture system 100 is attached to the insulin pen 102 as part of the setup sequence with each new pen, i.e., every 3 to 7 days (nominally 5 days) for a typical user. The durable portion 106 is attached to the insulin pen 102 first. The semi-disposable object 104 is then inserted into the distal opening 140 of the durable portion 106. The cannula 122 of the disposable portion 104 penetrates the distal bulkhead of the insulin pen 102, creating a fluid path across the TTOF sensing element. As the semi-disposable portion 104 is inserted into the durable portion 106, the electrical connector 118 mates with a corresponding electrical connector in the durable portion 106, creating an electrical connection to the TTOF sensor 116. When disposable portion 104, and therefore the pen needle cannula, penetrates septum 112, the pen needle is threaded onto distal threaded end 114, 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 usual manner to remove any trapped air.

[0024] In this embodiment, the assembly sequence is durable portion 106 first, semi-disposable portion 104 second, although one skilled in the art will appreciate that the system can be designed with a reversed assembly order. With this assembly sequence, durable portion 106 can be used on different insulin pens, such as one pen with a delayed-acting insulin and a second pen with a fast-acting insulin. Semi-disposable portion 104 preferably attaches to a universal ISO connection found on each insulin pen, and durable portion 106 is then attached to the semi-disposable portion 104 and the body of the insulin pen. Because durable portion 106 does not come into contact with the insulin, durable portion 106 can be swapped back and forth between multiple pens as needed for the user's treatment without affecting the sterility of the insulin. For treatments involving more than one insulin or medication, a means is provided to recognize additional medications with a durable attachment. For example, when the durable unit is attached to the pen, the camera on the smartphone paired with the durable portion is used to read the barcode on the injection pen.

[0025] The durable part 106 is preferably paired with the smartphone application as described above. The pairing procedure is preferably performed once for a given mobile phone 108 / durable part 106 pair. After the initial pairing, the application on the mobile phone 108 preferably automatically recognizes and communicates with the paired durable part 106.

[0026] Once installed on an insulin pen, the exemplary system automatically recognizes and captures dosage events as part of the user's normal injection sequence. Preferably, no additional usage steps beyond those required for normal insulin pen injections are required for the dosage sensor after initial setup on the pen. Dose volume and time are calculated by the durable portion 106. The durable portion 106 is preferably capable of storing many insulin pen minutes of dosage data. Data recorded by the durable portion 106 is preferably transferred to a smartphone 108 application whenever the smartphone 108 and durable portion 106 are within broadcast range of each other. Dosage data transferred to the smartphone 108 is preferably presented to the user in a convenient, easy-to-read format. Dosage information can also be transferred from the mobile phone to other diabetes management devices or to a cloud-based data storage site if further processing and analysis and transfer to other stakeholders in the patient's healthcare network are desired.

[0027] When the insulin pen 102 is emptied, the durable portion 106 is removed and prepared for the next use. The combination of the used insulin pen 102 and semi-disposable portion 104 is discarded similar to a conventional diabetes pen. The durable portion 106 or the semi-disposable portion 104 preferably has features to prevent reuse of the semi-disposable portion 104 on another insulin pen 102.

[0028] We next describe an exemplary smartphone 108 application. The smartphone application preferably displays dosage data to the user in an easy-to-understand format. FIG. 8A shows a dosage overview window, which can show recent dosage measurements and time-based averages. FIG. 8B has a dosage log that can be reviewed by the user for accuracy and provides a location for notes and other context-based data. FIG. 8C shows a graph of dosage measurements over a selectable time range, which can give the user trend insights.

[0029] Several aspects of insulin injections present significant challenges to measuring accurate doses. Insulin dose sizes can vary significantly, from as low as 3.3 microliters to as high as 800 microliters. Dose delivery times can vary significantly, from less than 1 second to more than 10 seconds, based on the size of the dose, the diameter and length of the needle used, the friction and mechanical efficiency of the insulin pen, and the actuation force applied by the user or the spring-loaded actuation of the pen. A typical insulin injection flow profile 500 is shown in FIG. 9. The flow profile has a sudden, large increase in flow 502 at the beginning of the injection, a continuously varying flow rate 504, and a relatively long flow decay 506 at the end of the dose. To calculate an accurate dose, the flow sensor must respond rapidly and accurately to all portions of the flow profile. The flow sensor must be able to respond to sudden changes in flow and be accurate over the range of flow rates that can be produced by a wide range of users. Advantageously, embodiments of the present invention are capable of determining doses by integrating flow measurements over time. Alternatively, several flow rate data points or the general shape of the flow curve can be matched to a stored table of dosage values, for example, incremental dosages from 1 unit to 60 units.

[0030] International standards currently require a volumetric accuracy equal to the insulin pen's minimum resolution or + / - 5% of the dose volume, whichever is greater. For example, for a typical U-100 pen with a 1U dial resolution, an accuracy of + / - 10 microliters is required for doses smaller than 200 microliters, and + / - 5% for doses larger than 200 microliters. Higher insulin concentrations are inversely proportional to volume. For example, a U-200 insulin pen with a 1U resolution would require a volumetric accuracy of + / - 5 microliters for doses smaller than 100 microliters, and + / - 2.5% for doses larger than 100 microliters.

[0031] For insulin injections, small diameter needles are typically used which can create relatively high back pressures, therefore, a flow sensor according to an embodiment of the present invention must be able to tolerate back pressures of up to 1 megapascal.

[0032] Because the flow sensor is in the insulin delivery pathway, it must be made from a material that is chemically compatible with insulin and must not react or be damaged in any way by insulin.

[0033] According to an exemplary embodiment of the present 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 both sides of the heating element. A time-varying signal of known amplitude, frequency, shape, and phase is applied to the central heater. The thermal signal diffuses through the fluid toward the sensor, where it is detected at both a reduced amplitude and a shifted phase relative to the drive signal. The amplitude signal corresponds to calorimeter sensing, while the phase-shifted signal corresponds to time-of-flight sensing. In the absence of flow, the thermal conduction zone around the heater is symmetrical, as shown in Figure 10. Electronic circuitry in the durable portion 106 senses balanced signals from the upstream and downstream sensors. The common signal received by both sensors, when filtered out by the electronic circuitry, calculates the no-flow condition for the sensor. In the presence of flow, the thermal zone is distorted by fluid convection, as shown in Figure 11. The thermal signal is unbalanced, and the electronic signal received at the downstream sensing element is phase (time) and amplitude shifted relative to the input and relative to the upstream sensor. Advantageously, the sensor signals from both the upstream and downstream sensor traces are sampled over the entire expected flow range during an infusion event. The shifted-in sensor signal is read by electronic circuitry in the durable portion 106 and converted to an instantaneous flow rate of insulin by referencing a stored calibration curve or table. Sampling the instantaneous flow rate at precise, frequent time intervals allows the total volume delivered to be calculated for each dose event. Figure 12 shows an example dose event and the associated data captured by the flow sensor to calculate the dose volume.

[0034] Several dose-tracking insulin pens are currently available on the market. These pens track and monitor the movement of the pen mechanism to determine the delivered dose. Traditional pens use a small display to communicate the intended dose volume of the current injection. Some newer models also incorporate wireless communication to smartphones. Because the pen's mechanization has inherent errors that can be additive to errors in the detection device, tracking the pen injection mechanism can fail to properly monitor the dose received by the user. Furthermore, user error, such as withdrawing the pen from the injection site before the dose is fully delivered to the tissue or failure of a system component, e.g., a pinched or clogged pen needle, can all contribute to not delivering the intended dose. Unlike traditional insulin pens, exemplary embodiments of the present invention utilize TTOF sensing to measure the actual time of delivery from the pen and the changing insulin flow profile, thereby enabling more complete and accurate information about the actual dose delivered.

[0035] A TTOF sensor measures the velocity of a fluid passing through the sensor. Therefore, the volume of fluid passing through a flow sensor that utilizes TTOF to measure fluid velocity depends on the cross-sectional area of ​​the flow path through which the fluid flows. As discussed above, injection-molded parts are limited in how precisely the flow path geometry can be made and how variable it can be from part to part. Embodiments of the present invention improve upon the disposable portion that interfaces between an insulin pen and a pen needle to measure flow from the insulin pen, through the disposable portion, into the pen needle, and to the patient. Metal tubing, as is known for needles and metal cannulas, can be manufactured relatively inexpensively and with high-precision inner diameters. Embodiments of the present invention advantageously utilize a metal cannula as the flow path through which fluid flows for flow measurement and dose recording.

[0036] An exemplary embodiment of the present invention forms a sensor on a glass substrate, which 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 preferable for liquid drug flow applications because one sensor surface is preferably exposed to the drug in the flow path, overcoming the limitations noted above with respect to thin film or bridge structures used in gaseous applications where pressure applied to the sensor is not an issue.

[0037] In another exemplary embodiment of the present invention, multiple sensor chips are used in tandem to increase the dynamic range of the sensor. FIG. 13 illustrates an alternative flow path 1800 having a first sensor 1802 and a second sensor 1804 downstream from the first sensor 1802. The flow path 1806 is provided with two different cross-sectional zones corresponding to the two sensor chips. The first sensor 1802 can be positioned in a relatively larger flow cross-section 1808 within the flow path 1806. This sensor will have better resolution at higher flow rates due to the relatively lower flow rate. The second sensor 1804 is positioned downstream of the first sensor 1802 in an area of ​​the flow path 1806 having a smaller cross-section 1810. The second sensor 1804 will have better resolution at lower flow rates due to the relatively higher flow rate. Of course, those skilled in the art will readily appreciate that more than two sensors can be used to further improve the dynamic range if necessary. The dose sensing algorithm determines the appropriate sensor pair to power and read the signal based on the measured flow conditions and trends.

Claims

1. a proximal end shaped to connect to an insulin pen, the proximal end having a piercing member extending therefrom; a distal end shaped to connect to a pen needle and having a septum; a metal flow path having a circular cross-section near the proximal end and a rectangular cross-section near the distal end, the metal flow path extending from the proximal end to the distal end with a smooth transition between the circular cross-section and the rectangular cross-section, the metal flow path having a sensor window in the rectangular cross-section; a flow manifold including: a flow sensor located within the sensor window that senses the velocity of fluid flowing through the metal flow channel; Equipped with A flow sensor assembly wherein a surface of the flow sensor does not protrude into the metal flow path.

2. A proximal end shaped to connect to an insulin pen, the proximal end having a puncture member extending from the proximal end, a distal end opposite the proximal end, the proximal end having a circular cross-sectional portion near the proximal end and a rectangular cross-sectional portion near the distal end, and a step of forming a metal flow path extending from the proximal end to the distal end so that there is a smooth transition between the circular cross-sectional portion and the rectangular cross-sectional portion; forming a sensor window in a sidewall of the rectangular cross-sectional portion of the metal flow path; injection molding a flow manifold around the metal flow passages; mounting a flow sensor within the sensor window; Equipped with A method of manufacturing a flow sensor assembly, wherein a surface of the flow sensor does not protrude into the metal flow path.

3. The step of injection molding the flow manifold comprises:

3. The method of manufacturing a flow sensor assembly of claim 2, including forming an insulin pen connector at the proximal end of the flow manifold.

4. The step of injection molding the flow manifold comprises: The method of manufacturing a flow sensor assembly of claim 2 including forming a threaded pen needle connector at a distal end of the flow manifold.

5. The method of manufacturing a flow sensor assembly of claim 4 further comprising the step of attaching a bulkhead to the distal end of the flow manifold.

Images