Arrangement for detecting a position of a plunger
11786657 · 2023-10-17
Assignee
Inventors
- Paul Richard Draper (Worcestershire, GB)
- Anthony Paul Morris (Coventry, GB)
- Stephen Francis Gilmore (Bristol, GB)
Cpc classification
A61M5/3146
HUMAN NECESSITIES
A61M5/20
HUMAN NECESSITIES
G01D5/32
PHYSICS
International classification
A61M5/20
HUMAN NECESSITIES
A61M5/145
HUMAN NECESSITIES
G01D5/32
PHYSICS
Abstract
The invention relates to an arrangement for detecting a position of a plunger (4) relative to a bung (3) in a drug cartridge (1), comprising a proximity sensor (5) located close to a distal end (6) of the plunger (4) facing the bung (3) and aligned to receive light reflected by the bung (3).
Claims
1. A medical device comprising: a bung having a proximal face comprising one or more protrusions; and a proximity sensor located within or on a plunger at a distal end of the plunger adjacent to the bung, the proximity sensor configured to move with the plunger as the plunger moves towards the bung, and the proximity sensor aligned to receive light reflected by the one or more protrusions of the bung, wherein the received reflected light is used to detect a position of the plunger relative to the bung in a drug cartridge of the medical device.
2. The medical device of claim 1, wherein the proximity sensor comprises a light source and a light sensor.
3. The medical device of claim 2, wherein the light source and the light sensor are arranged in compartments within the plunger which are optically isolated from each other such that light emitted from the light source is prevented from directly illuminating the light sensor.
4. The medical device of claim 2, wherein the proximity sensor is coupled to the plunger such that the proximity sensor moves with the plunger as the plunger moves towards the bung.
5. The medical device of claim 1, wherein the proximity sensor comprises a lens.
6. The medical device of claim 5, wherein the distal end of the plunger is arranged as the lens of the proximity sensor.
7. The medical device of claim 1, wherein the proximity sensor comprises an open face.
8. The medical device of claim 1, wherein a processing unit for processing images acquired by the proximity sensor is integrated with the proximity sensor.
9. The medical device of claim 1, wherein a processing unit for processing images acquired by the proximity sensor is external to the proximity sensor.
10. The medical device of claim 1, wherein a processing unit is configured to determine a first contact between plunger and bung, and wherein the processing unit is further configured to stop a movement of the plunger upon detection of the first contact.
11. The medical device of claim 1, wherein the distal end of the plunger is substantially flat.
12. The medical device of claim 1, further comprising an electromechanical drive for displacing the plunger.
13. The medical device of claim 12, wherein a control unit is configured for causing the electromechanical drive to advance the plunger towards the bung and stop the electromechanical drive when the proximity sensor detects contact with the plunger.
14. The medical device of claim 1, wherein a home or a start position of the plunger in the medical device is positioned in axial clearance from the proximal face of the bung.
15. The medical device of claim 1, wherein the distal end of the plunger is covered by a transparent plate.
16. The medical device of claim 15, wherein the proximity sensor is configured as a light sensor and located behind the transparent plate.
17. The medical device of claim 1, wherein the one or more protrusions are configured to deform upon contact with the plunger.
18. The medical device of claim 17, wherein the proximity sensor is configured to detect the position of the plunger relative to the bung based on the deformation of the one or more protrusions.
19. The medical device of claim 1, wherein the one or more protrusions are one or more proximally-extending protrusions having at least one of a circle-shape, an elliptical-shape, a cross-shape, or a rectangular-shape.
20. The medical device of claim 1, wherein the drug cartridge comprises a drug containing at least one pharmaceutically active compound.
21. A medical device comprising: a bung having a proximal face comprising one or more protrusions; and a proximity sensor located within or on a plunger at a distal end of the plunger adjacent to the bung and aligned to receive light reflected by the one or more protrusions of the bung, wherein the received reflected light is used to detect a position of the plunger relative to the bung in a drug cartridge of the medical device, wherein the proximity sensor is configured to detect light both (i) prior to a contact between the plunger and the bung and (ii) upon the contact between the plunger and the bung, and wherein the detected light prior to the contact is associated with a signal from the proximity sensor being above a threshold and the detected light upon the contact is associated with the signal from the proximity sensor being below the threshold.
22. The medical device of claim 21, wherein the one or more protrusions are configured to deform upon contact with the plunger, and the proximity sensor is configured to detect the position of the plunger relative to the bung based on the deformation of the one or more protrusions.
23. The medical device of claim 22, wherein the proximity sensor is configured to detect the position of the plunger relative to the bung based on the deformation of the one or more protrusions in at least one image captured by the proximity sensor.
24. The medical device of claim 21, wherein the drug cartridge comprises a drug containing at least one pharmaceutically active compound.
25. A method comprising: receiving light using a proximity sensor of a medical device located within or on a plunger of the medical device at a distal end of the plunger, the received light being reflected by one or more protrusions on a proximal face of a bung of the medical device, the proximity sensor configured to move with the plunger as the plunger moves towards the bung; and detecting a position of the plunger relative to the bung based on the received light.
26. The method of claim 25, further comprising: advancing the plunger of the medical device towards the bung of the medical device; and stopping the advancement of the plunger when the detected position of the plunger relative to the bung represents a contact between the plunger and the bung.
27. The method of claim 25, further comprising: advancing the plunger of the medical device, using an electromechanical drive of the medical device, towards the bung of the medical device; and stopping the advancement of the plunger, using the electromechanical drive, when the detected position of the plunger relative to the bung represents a contact between the plunger and the bung.
28. The method of claim 25, wherein detecting the position of the plunger relative to the bung based on the received light comprises detecting when a protruding surface of the bung comes in contact with the plunger based on the received light.
29. The method of claim 25, comprising deforming the one or more protrusions on the proximal face of the bung.
30. The method of claim 29, wherein the light is received while deforming the one or more protrusions on the proximal face of the bung.
31. The method of claim 29, wherein the one or more protrusions are one or more proximally-extending protrusions having at least one of a circle-shape, an elliptical-shape, a cross-shape, or a rectangular-shape.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
(1) The present invention will become more fully understood from the detailed description given herein below and the accompanying drawings which are given by way of illustration only, and thus, are not limitive of the present invention, and wherein:
(2)
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(4)
(5)
(6)
(7)
(8)
(9)
(10)
(11) Corresponding parts are marked with the same reference symbols in all figures.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
(12)
(13) A proximity sensor 5 arranged as an imaging sensor is disposed within the plunger 4. The proximity sensor 5 can be of any type suitable for imaging, but preferentially may be of the type comprising a light source, light sensor, lens and processing unit. The proximity sensor 5 is located close to a flat transparent distal end 6 of the plunger 4 facing the bung 3 and aligned to image the bung 3.
(14)
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(18) The processing unit may be integrated with the proximity sensor 5 or arranged as an additional device. The proximity sensor 5 may be connected to the processing unit and/or other electronic equipment by a cable 10 arranged within the plunger 4.
(19) The cartridge 1 and plunger 4 may be part of a drug delivery device (not illustrated). The drug delivery device may comprise a body adapted to receive the cartridge 1. A hypodermic needle may be attached to the cartridge 1, preferably a needle with two tips, one of them for piercing an injection site and the other for piercing the septum 2 on the cartridge 1 for establishing a fluid communication between the cartridge 1 and the needle. The drug delivery device may further comprise at least one electric unit or electronic device (not illustrated) such as a control unit and/or a human-machine-interface for communicating information to a user and for allowing the user to operate the drug delivery device and an electromechanical drive (not illustrated) for inserting the needle into an injection site, e.g. a patient's skin and/or dispensing drug from the cartridge 1 through the needle and/or retracting the needle post-injection. The electromechanical drive may comprise motor driven gear boxes driving simple power screws or telescopic power screws.
(20) In order to properly position the plunger 4 at the bung 3 prior to dispensing the drug the plunger 4 is driven towards the bung 3 with the proximity sensor 5 actively imaging. Images 9 from the proximity sensor 5 are processed to determine the first presence of the protruding surface structure 8 of the bung 3 in contact with the plunger 4. As soon as this condition is met the plunger 4 is stopped.
(21) In an exemplary embodiment the transparent distal end 6 of the plunger 4 may not be flat but arranged as a lens for the proximity sensor 5. This may simplify the optics and the manufacturing and thus reduce costs.
(22)
(23) A proximity sensor 5 comprising a light source 5.1, e.g. a light emitting diode, and a light sensor 5.2, e.g. a light sensitive resistor, is disposed within the plunger 4.
(24) The light source 5.1 and the light sensor 5.2 are arranged in compartments 4.1, 4.2 within the plunger 4 which are optically isolated from each other such that light emitted from the light source 5.1 cannot directly illuminate the light sensor 5.2.
(25) The compartments 4.1, 4.2 are open at the distal end of the plunger 4 facing the bung 3.
(26) A processing unit may be integrated with the proximity sensor 5 or arranged as an additional device. The proximity sensor 5 may be connected to the processing unit and/or other electronic equipment by a cable 10 arranged within the plunger 4.
(27) Prior to contact with the bung 3, light emitted from the light source 5.1 is reflected by the bung 3 and detected by the light sensor 5.2. At the point where the plunger contacts the surface of the bung 3, both compartments are covered over and optically isolated from each other. At this point light is no longer received at the light sensor 5.2. This enables detection of contact between the plunger 4 and the bung 3, e.g. by means of the processing unit. Thus, when the light detected by the light sensor 5.2 is below a threshold, the processing unit determines that contact between the plunger 4 and the bung 3 is made, for example by detecting that a signal level of an electrical signal generated by the light sensor 5.2 is below a predetermined threshold.
(28) In order to properly position the plunger 4 at the bung 3 prior to dispensing the drug the plunger 4 is driven towards the bung 3 with the proximity sensor 5 receiving light. Responses from the proximity sensor 5 are processed to determine the first contact of the bung 3 with the plunger 4. As soon as this condition is met the plunger 4 is stopped.
(29) The term “drug” or “medicament”, as used herein, means a pharmaceutical formulation containing at least one pharmaceutically active compound,
(30) wherein in one embodiment the pharmaceutically active compound has a molecular weight up to 1500 Da and/or is a peptide, a protein, a polysaccharide, a vaccine, a DNA, a RNA, an enzyme, an antibody or a fragment thereof, a hormone or an oligonucleotide, or a mixture of the above-mentioned pharmaceutically active compound,
(31) wherein in a further embodiment the pharmaceutically active compound is useful for the treatment and/or prophylaxis of diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism, acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis,
(32) wherein in a further embodiment the pharmaceutically active compound comprises at least one peptide for the treatment and/or prophylaxis of diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy,
(33) wherein in a further embodiment the pharmaceutically active compound comprises at least one human insulin or a human insulin analogue or derivative, glucagon-like peptide (GLP-1) or an analogue or derivative thereof, or exendin-3 or exendin-4 or an analogue or derivative of exendin-3 or exendin-4.
(34) Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) human insulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) human insulin; Asp(B28) human insulin; human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.
(35) Insulin derivates are for example B29-N-myristoyl-des(B30) human insulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N—(N-palmitoyl-Y-glutamyl)-des(B30) human insulin; B29-N—(N-lithocholyl-Y-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin.
(36) Exendin-4 for example means Exendin-4(1-39), a peptide of the sequence H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.
(37) Exendin-4 derivatives are for example selected from the following list of compounds:
(38) H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,
(39) H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,
(40) des Pro36 Exendin-4(1-39),
(41) des Pro36 [Asp28] Exendin-4(1-39),
(42) des Pro36 [IsoAsp28] Exendin-4(1-39),
(43) des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),
(44) des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),
(45) des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),
(46) des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),
(47) des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),
(48) des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or
(49) des Pro36 [Asp28] Exendin-4(1-39),
(50) des Pro36 [IsoAsp28] Exendin-4(1-39),
(51) des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),
(52) des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),
(53) des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),
(54) des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),
(55) des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),
(56) des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),
(57) wherein the group -Lys6-NH2 may be bound to the C-terminus of the Exendin-4 derivative;
(58) or an Exendin-4 derivative of the sequence
(59) des Pro36 Exendin-4(1-39)-Lys6-NH2 (AVE0010),
(60) H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,
(61) des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,
(62) H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,
(63) H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,
(64) des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,
(65) H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,
(66) H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,
(67) H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,
(68) H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,
(69) H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,
(70) H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,
(71) des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,
(72) H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,
(73) H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,
(74) H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,
(75) des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,
(76) H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,
(77) H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,
(78) des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,
(79) H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,
(80) H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,
(81) H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,
(82) H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25] Exendin-4(1-39)-NH2,
(83) H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,
(84) H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,
(85) des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,
(86) H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(S1-39)-(Lys)6-NH2
(87) H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2;
(88) or a pharmaceutically acceptable salt or solvate of any one of the afore-mentioned Exendin-4 derivative.
(89) Hormones are for example hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists as listed in Rote Liste, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, Goserelin.
(90) A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid, a heparin, a low molecular weight heparin or an ultra low molecular weight heparin or a derivative thereof, or a sulphated, e.g. a poly-sulphated form of the above-mentioned polysaccharides, and/or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of a poly-sulphated low molecular weight heparin is enoxaparin sodium.
(91) Antibodies are globular plasma proteins (˜150 kDa) that are also known as immunoglobulins which share a basic structure. As they have sugar chains added to amino acid residues, they are glycoproteins. The basic functional unit of each antibody is an immunoglobulin (Ig) monomer (containing only one Ig unit); secreted antibodies can also be dimeric with two Ig units as with IgA, tetrameric with four Ig units like teleost fish IgM, or pentameric with five Ig units, like mammalian IgM.
(92) The Ig monomer is a “Y”-shaped molecule that consists of four polypeptide chains; two identical heavy chains and two identical light chains connected by disulfide bonds between cysteine residues. Each heavy chain is about 440 amino acids long; each light chain is about 220 amino acids long. Heavy and light chains each contain intrachain disulfide bonds which stabilize their folding. Each chain is composed of structural domains called Ig domains. These domains contain about 70-110 amino acids and are classified into different categories (for example, variable or V, and constant or C) according to their size and function. They have a characteristic immunoglobulin fold in which two β sheets create a “sandwich” shape, held together by interactions between conserved cysteines and other charged amino acids.
(93) There are five types of mammalian Ig heavy chain denoted by α, β, ε, γ, and μ. The type of heavy chain present defines the isotype of antibody; these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies, respectively.
(94) Distinct heavy chains differ in size and composition; α and γ contain approximately 450 amino acids and δ approximately 500 amino acids, while μ and ε have approximately 550 amino acids. Each heavy chain has two regions, the constant region (C.sub.H) and the variable region (V.sub.H). In one species, the constant region is essentially identical in all antibodies of the same isotype, but differs in antibodies of different isotypes. Heavy chains γ, α and δ have a constant region composed of three tandem Ig domains, and a hinge region for added flexibility; heavy chains μ and ε have a constant region composed of four immunoglobulin domains. The variable region of the heavy chain differs in antibodies produced by different B cells, but is the same for all antibodies produced by a single B cell or B cell clone. The variable region of each heavy chain is approximately 110 amino acids long and is composed of a single Ig domain.
(95) In mammals, there are two types of immunoglobulin light chain denoted by λ and κ. A light chain has two successive domains: one constant domain (CL) and one variable domain (VL). The approximate length of a light chain is 211 to 217 amino acids. Each antibody contains two light chains that are always identical; only one type of light chain, κ or λ, is present per antibody in mammals.
(96) Although the general structure of all antibodies is very similar, the unique property of a given antibody is determined by the variable (V) regions, as detailed above. More specifically, variable loops, three each the light (VL) and three on the heavy (VH) chain, are responsible for binding to the antigen, i.e. for its antigen specificity. These loops are referred to as the Complementarity Determining Regions (CDRs). Because CDRs from both VH and VL domains contribute to the antigen-binding site, it is the combination of the heavy and the light chains, and not either alone, that determines the final antigen specificity.
(97) An “antibody fragment” contains at least one antigen binding fragment as defined above, and exhibits essentially the same function and specificity as the complete antibody of which the fragment is derived from. Limited proteolytic digestion with papain cleaves the Ig prototype into three fragments. Two identical amino terminal fragments, each containing one entire L chain and about half an H chain, are the antigen binding fragments (Fab). The third fragment, similar in size but containing the carboxyl terminal half of both heavy chains with their interchain disulfide bond, is the crystalizable fragment (Fc). The Fc contains carbohydrates, complement-binding, and FcR-binding sites. Limited pepsin digestion yields a single F(ab′)2 fragment containing both Fab pieces and the hinge region, including the H-H interchain disulfide bond. F(ab′)2 is divalent for antigen binding. The disulfide bond of F(ab′)2 may be cleaved in order to obtain Fab′. Moreover, the variable regions of the heavy and light chains can be fused together to form a single chain variable fragment (scFv).
(98) Pharmaceutically acceptable salts are for example acid addition salts and basic salts. Acid addition salts are e.g. HCl or HBr salts. Basic salts are e.g. salts having a cation selected from alkali or alkaline, e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), wherein R1 to R4 independently of each other mean: hydrogen, an optionally substituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenyl group, an optionally substituted C6-C10-aryl group, or an optionally substituted C6-C10-heteroaryl group. Further examples of pharmaceutically acceptable salts are described in “Remington's Pharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), Mark Publishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia of Pharmaceutical Technology.
(99) Pharmaceutically acceptable solvates are for example hydrates.
(100) Those of skill in the art will understand that modifications (additions and/or removals) of various components of the apparatuses, methods and/or systems and embodiments described herein may be made without departing from the full scope and spirit of the present invention, which encompass such modifications and any and all equivalents thereof.
LIST OF REFERENCES
(101) 1 cartridge 2 septum 3 bung 4 plunger 4.1 compartment 4.2 compartment 5 proximity sensor 5.1 light source 5.2 light sensor 6 transparent distal end 7 flat proximal face 8 surface structure 9 image 10 cable D distal direction P proximal direction