U.S. patent application number 12/231319 was filed with the patent office on 2009-06-11 for system for dispensing biological fluids.
Invention is credited to James W. Baker, Gary A. Kirian.
Application Number | 20090145509 12/231319 |
Document ID | / |
Family ID | 35995187 |
Filed Date | 2009-06-11 |
United States Patent
Application |
20090145509 |
Kind Code |
A1 |
Baker; James W. ; et
al. |
June 11, 2009 |
System for dispensing biological fluids
Abstract
Systems, including methods and apparatus, for dispensing
biological fluids, such as allergens.
Inventors: |
Baker; James W.; (Lake
Oswego, OR) ; Kirian; Gary A.; (Lake Oswego,
OR) |
Correspondence
Address: |
KOLISCH HARTWELL, P.C.
200 PACIFIC BUILDING, 520 SW YAMHILL STREET
PORTLAND
OR
97204
US
|
Family ID: |
35995187 |
Appl. No.: |
12/231319 |
Filed: |
August 29, 2008 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
11678005 |
Feb 22, 2007 |
7418981 |
|
|
12231319 |
|
|
|
|
PCT/US2005/031385 |
Sep 2, 2005 |
|
|
|
11678005 |
|
|
|
|
Current U.S.
Class: |
141/2 ;
141/27 |
Current CPC
Class: |
A61J 1/2096 20130101;
A61M 5/1452 20130101; A61M 5/14216 20130101; A61M 39/223 20130101;
A61J 1/2062 20150501; A61J 1/2058 20150501; A61J 1/2055 20150501;
A61J 1/201 20150501; A61J 1/2089 20130101 |
Class at
Publication: |
141/2 ;
141/27 |
International
Class: |
B65B 1/04 20060101
B65B001/04; B65B 31/04 20060101 B65B031/04 |
Claims
1. A method of dispensing biological fluid, comprising: operating
at least one cooling device to refrigerate a plurality of sealed
stock vials disposed in an array in a housing, the stock vials
holding biological fluids; blowing filtered air into a compartment
disposed below a stock vial disposed in the housing; and
transferring an aliquot of a biological fluid held by the stock
vial, out through a resilient closure of the stock vial and into a
syringe pump disposed in the compartment.
2. The method of claim 1, wherein the step of blowing filtered air
includes a step of filtering air to remove microorganisms.
3. The method of claim 2, where the step of filtering air includes
a step of filtering air with a HEPA filter.
4. The method of claim 1, where the step of blowing filtered air
includes a step of creating a positive pressure in the compartment
with the filtered air to reduce entry of unfiltered air into the
compartment.
5. The method of claim 1, wherein the stock vial is disposed in a
vessel storage compartment in the housing, further comprising a
step of blowing filtered air into the vessel storage
compartment.
6. The method of claim 1, further comprising a step of disposing at
least one stock vial in the housing such that a label and/or a
fluid level of the at least one stock vial is visible from outside
the housing.
7. The method of claim 6, wherein the step of disposing includes a
step of disposing the at least one stock vial behind a transparent
wall of the housing such that at least a portion of the at least
one stock vial is visible through the transparent wall.
8. The method of claim 1, further comprising a step of disposing
the stock vials in the array, with each stock vial in an inverted
configuration.
9. The method of claim 1, wherein the step of transferring includes
a step of transferring at least a portion of the aliquot from the
syringe pump to a receiver vial, through a resilient closure of the
receiver vial.
10. The method of claim 1, wherein the step of transferring is
performed a plurality of times with aliquots of different
biological fluids to form a mixture of the different biological
fluids.
11. The method of claim 10, wherein the step of transferring
performed a plurality of times includes a step of transferring
allergens to make an allergen mixture for an allergy patient.
12. The method of claim 1, wherein the housing is connected to a
base, further comprising a step of rotating the array of stock
vials relative to the base in order to select the stock vial from
which the aliquot is to be transferred.
13. The method of claim 1, wherein the step of transferring
includes a step of automatically operating a power-driven syringe
pump.
14. The method of claim 1, further comprising a step of inputting
instructions for the step of transferring to a controller that
controls operation of the syringe pump.
15. The method of claim 14, wherein the step of inputting
instructions includes a step of inputting instructions to the
controller via a touchscreen.
16. A system for dispensing biological fluid, comprising: a housing
for holding an array of sealed stock vials containing biological
fluids; at least one cooling device operatively coupled to the
housing and configured to refrigerate the stock vials with the
stock vials disposed in the housing; a blower mechanism for blowing
filtered air into a compartment disposed below a stock vial
disposed in the housing; a syringe pump for transferring an aliquot
of a biological fluid contained by the stock vial, out through a
resilient closure of the stock vial and into a syringe pump
disposed in the compartment; and a controller operatively coupled
to the syringe pump and configured to control transfer of the
aliquot by the syringe pump.
17. The system of claim 16, wherein the blower mechanism includes a
filter for removing microorganisms from air.
18. The system of claim 16, wherein the blower mechanism includes a
HEPA filter.
19. The system of claim 16, further comprising a base connected to
the housing, wherein the housing is pivotable relative to the base
for selection of the stock vial.
20. The system of claim 16, wherein the at least one cooling device
includes at least one thermoelectric cooling device.
Description
CROSS-REFERENCES
[0001] This application is a continuation of U.S. patent
application Ser. No. 11/678,005, filed Feb. 22, 2007, now U.S. Pat.
No. 7,418,981, which in turn is a continuation of PCT Patent
Application Serial No. PCT/US05/31385, filed Sep. 2, 2005, now
expired, which in turn claims priority under U.S. and international
law (including but not limited to the Paris Convention and 35
U.S.C. .sctn. 120) to U.S. patent application Ser. No. 10/933,849,
filed Sep. 2, 2004, now U.S. Pat. No. 7,398,802. These applications
are incorporated herein by reference in their entireties for all
purposes.
INTRODUCTION
[0002] An allergy is an untoward reaction of the body's immune
system to a foreign substance. The foreign substance may be known
as an allergen (an allergy generating substance) and/or an antigen
(an antibody generating substance). The immune system is made up of
two parts: the antibody-mediated system and the cell-mediated
system. Allergic reactions to allergens have been classified into
four major types (see Table 1). Three of these may involve the
antibody-mediated system and one may involve the cell-mediated
system.
TABLE-US-00001 TABLE 1 Exemplary Types of Allergic Reactions Immune
System Antigens Type Involvement (Allergens) Exemplary Diseases
Type 1 Immunoglobulin E Pets (dander), Allergic rhinitis, (IgE)
dust, mold, pollen, asthma, eczema, medications, anaphylaxis,
venoms, foods Type 2 Immunoglobulin G Drugs, other Hemolytic anemia
(IgG) chemicals Type 3 Immunoglobulin G Drugs, other
Glomerulonephritis (IgG) chemicals Type 4 Lymphocytes Various
chemicals Contact dermatitis (poison ivy)
[0003] In the case of type 1 mediated allergy, allergens such as
animal (pet) dander, dust mite antigen, mold, and/or pollen may
combine with IgE antibodies on the surface of white blood cells
known as mast cells. These cells then may secrete a number of
chemicals including histamine which may cause hives, itchy watery
eyes, nasal congestion, nasal discharge, throat swelling, coughing,
wheezing, shortness of breath, gastrointestinal symptoms, and/or a
shock-like state. A medical history and a physical from a patient
with allergy symptoms may be used by a practitioner to make a
presumptive diagnosis of type 1 mediated allergic disease. This
diagnosis may be confirmed with skin tests and/or blood tests (RAST
test) to test for the presence of antigen-specific IgE.
[0004] Management of allergic disease involves three major
strategies: avoidance of the allergen, medications to block the
allergic reaction, and/or immunotherapy. Of these, immunotherapy
may be the most practical and effective, because it involves
long-term desensitization to particular allergens by systemic
exposure to controlled levels of these allergens. Immunotherapy
involves making a vaccine from the various allergen extracts to
which a patient is sensitive. For example, the patient might have
positive skin tests to extracts from tree pollen, grass pollen, and
cat dander. A vaccine may be prepared by mixing these extracts in a
vial (the "patient's vial") and then diluting the mixed extracts to
a level that the patient can tolerate for injection. Immunotherapy
generally involves injection of increasing doses (decreasing
dilutions) of the mixture over time, such as over the course of
months or years, to a level that may be much higher than (in some
cases several orders of magnitude greater than) the initial dose.
This approach decreases the sensitivity of the patient to the
injected mixture (and thus the injected allergens) and hopefully
helps control the underlying allergic disease.
[0005] At present, most practitioners mix extracts using individual
syringes to transfer specific amounts and concentrations of
extracts from stock bottles to the patient's vial. Since the
allergen mixture, or a dilution thereof, may be injected into the
patient, the desired allergens/extracts generally are combined in
the patient's vial under sterile conditions.
[0006] FIG. 1 shows a series of configurations produced by
performance of a common method 20 for sterile transfer of a
selected allergen 22. The allergen 22 may be provided as a sterile
extract in liquid, contained in a stock vial 24. The stock vial may
be generally transparent and may be sealed at its mouth with a
closure 26, such as a resilient (elastomeric) septum 28. Septum 28
may be held in place by a retainer 30 extending around the neck of
the vial 24, and particularly around a collar or flange formed on
the neck of the vial. Retainer 30 also may extend partially over
the exterior surface of the septum to leave an exposed region 32 of
the septum for access to the interior of the vial with a
hollow-bore needle (or other conduit). The needle may be used to
pierce the septum, to provide fluid communication with the interior
(the fluid contents) of the vial. Since the septum is elastomeric,
after the needle pierces the septum, the needle and septum may be
disposed in sealed engagement, circumferentially around the needle,
in a configuration that prevents fluid leakage around the needle.
The allergen 22 may be transferred to a patient's vial 34, which
may be of generally similar construction to the stock vial, but
often smaller in size. Transfer may be performed with a syringe 36
having a barrel 38 with graduations for volume measurement and a
hollow-bore needle 40 for penetration of septum 28.
[0007] Configuration 42 shows stock vial 24 prepared to receive
needle 40 of the syringe. Stock vial 24 may be in an upright or
inverted configuration. Exposed region 32 of the septum and the
exterior surface of the needle may carry microorganisms that would
contaminate the transferred fluid. Accordingly, the exterior
surface of the septum may be disinfected by wiping this surface
with alcohol prior to penetration with the needle, and the needle
may be obtained in a sterile condition, such as by treatment with
heat, steam, a chemical, and/or electromagnetic radiation, among
others. Furthermore, the stock vial, the syringe, and the patient's
vial may be disposed in a laminar flow hood equipped with
bacteriostatic illumination before, during, and/or after
performance of the steps illustrated in FIG. 1.
[0008] Configuration 44 shows stock vial 24 placed in fluid
communication with syringe 36 by insertion of the needle through
the septum and into contact with the allergen. A plunger 46 of the
syringe has been moved outward within the barrel to load a measured
volume of the allergen, shown at 47, from the stock vial into
barrel 38.
[0009] Configuration 48 shows syringe 36 removed from the stock
vial and holding measured volume 47 of the allergen and positioned
above patient's vial 34. The patient's vial also may be disinfected
on the exterior surface where the syringe will penetrate a septum
50 of this vial, particularly if the patient's vial has already
received other allergens in separate dispensing operations.
[0010] Configuration 52 shows syringe 36 placed in fluid
communication with the patient's vial by penetration of the septum
of the patient's vial with needle 40 of the syringe. Plunger 46 may
be moved inward within barrel 38 of the syringe to expel the
measured volume of the allergen from the syringe barrel into the
patient's vial.
[0011] The method shown here may be repeated for each selected
extract to introduce a desired set and ratio of allergens into the
patient's vial and thus to form a custom mixture for further
dilution and/or injection into a patient. However, this commonly
used method for preparation of allergen mixtures may have a number
of drawbacks. Generally, each stock vial may be placed at room
temperature from refrigerated storage, and allowed to remain at
room temperature and exposed to light before and during formation
of allergen mixtures. In some cases, the stock vials may sit at
room temperature, exposed to light, for many hours as various
allergen mixtures are being prepared. Over time, the allergens in
the stock vials thus may be physically and/or chemically damaged
(such as denaturation, oxidation, and/or cleavage of allergen
proteins), with unpredictable changes in allergen potency that may
affect diagnosis or treatment of patients using the allergens.
Furthermore, this common method of preparing allergen mixtures may
be too labor intensive, wasteful of syringes, unsafe, and/or prone
to contamination and/or human error, among others.
SUMMARY
[0012] The present teachings provide systems, including methods and
apparatus, for dispensing biological fluids, such as allergens.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] FIG. 1 is a series of configurations produced by performance
of a common method for sterile transfer of an allergen extract from
a stock vial to a patient's vial so that a customized mixture of
allergens can be prepared for further dilution and/or injection
into a patient.
[0014] FIG. 2 is a schematic view of an exemplary system for
dispensing biological fluids, in accordance with aspects of the
present teachings.
[0015] FIG. 3 is a schematic view of an exemplary dispenser station
of the system of FIG. 2, including a fluidics mechanism that
provides fluid transfer from a supply vial to a receiver vial, and
a set of additional features that may be included in the dispenser
station in any suitable combination, in accordance with aspects of
the present teachings.
[0016] FIG. 4 is a schematic view of a thermal control system of
the system of FIG. 2.
[0017] FIG. 5 is a schematic view of another exemplary system for
dispensing biological fluids, in accordance with aspects of the
present teachings.
[0018] FIG. 6 is a somewhat schematic view of a dispenser station
from the system of FIG. 5.
[0019] FIG. 7 is a somewhat schematic view of another exemplary
dispenser station that may be included in the systems of the
present teachings.
[0020] FIG. 8 is a perspective view of an example of a system for
dispensing measured volumes of biological fluids between vials
under relatively sterile conditions, in accordance with aspects of
the present teachings.
[0021] FIG. 9 is a sectional view of the system of FIG. 8, taken
generally along line 9-9 of FIG. 8, in the absence of supply
vials.
[0022] FIG. 10 is a partially exploded, fragmentary sectional view
of the system of FIG. 8, taken generally along line 10-10 of FIG.
8.
[0023] FIG. 11 is a top plan view of a dispenser retainer of the
system of FIG. 8, taken generally along line 11-11 of FIG. 10.
[0024] FIG. 12 is fragmentary sectional view of selected portions
of the system of FIG. 8, taken generally along line 12-12 of FIG.
10.
[0025] FIG. 13 is a side elevation view of a dispenser station of
the system of FIG. 8, viewed generally as in FIG. 10, with the
dispenser station in a loading configuration and with a portion of
a housing of the dispenser station removed, in accordance with
aspects of the present teachings.
[0026] FIG. 14 is a side elevation view of a dispenser station of
the system of FIG. 8, viewed generally as in FIG. 10, with the
dispenser station in a delivery configuration and with a portion of
a housing of the dispenser station removed, in accordance with
aspects of the present teachings.
[0027] FIG. 15 is a fragmentary view of selected portions of the
dispenser station of FIG. 13, particularly a valve of the dispenser
station, taken generally at "15" in FIG. 13.
[0028] FIG. 16 is a fragmentary view of selected portions of the
dispenser station of FIG. 14, particularly a valve of the dispenser
station, taken generally as in FIG. 15.
[0029] FIG. 17 is fragmentary view of selected portions of the
dispenser station of FIG. 14, particularly a valve of the dispenser
station, taken generally as in FIG. 16 but from an opposing
(exterior) side of the housing.
[0030] FIG. 18 is a side elevation view from the front of the
dispenser station of FIG. 13, taken generally along line 18-18 of
FIG. 13 with the housing assembled.
[0031] FIG. 19 is a view of another exemplary system for dispensing
biological fluids, in accordance with aspects of the present
teachings.
[0032] FIG. 20 is a bottom sectional view of the system of FIG. 19,
taken generally along line 20-20 of FIG. 19 and showing a set of
individually thermally regulated compartments each including a
jacket structure for receiving supply vessels.
[0033] FIG. 21 is a view of the jacket structure of FIG. 20, taken
generally from the side and above the jacket structure.
[0034] FIG. 22 is a top view of the system of FIG. 19, with the
cover of the system removed such that portions of a thermal control
system are visible.
[0035] FIG. 23 is a sectional view of the system of FIG. 19, taken
generally along line 23-23 of FIG. 22 and showing portions of an
individual thermal control unit of the thermal control system.
[0036] FIG. 24 is a partially sectional side view of a dispenser
station from the system of FIG. 19, in accordance with aspects of
the present teachings.
[0037] FIG. 25 is a somewhat schematic view of selected portions of
the dispenser station of FIG. 24 and showing a valve configuration
produced in the dispenser station as a syringe pump of the
dispenser station is loading fluid, in accordance with aspects of
the present teachings.
[0038] FIG. 26 is a somewhat schematic view of selected portions of
the dispenser station of FIG. 24 and showing a valve configuration
produced in the dispenser station as the syringe pump is delivering
fluid, in accordance with aspects of the present teachings
[0039] FIG. 27 is a somewhat schematic, partially sectional side
view of an exemplary dispenser station including a flow system that
cools and pressurizes a housing compartment of the dispenser
station, in accordance with aspects of the present teachings.
[0040] FIG. 28 is a somewhat schematic, partially sectional side
view of an exemplary dispenser station including a decontamination
mechanism, in accordance with aspects of the present teachings.
[0041] FIG. 29 is a somewhat schematic side view of an exemplary
dispenser station with a pinch valve arrangement that is operated
manually, in accordance with aspects of the present teachings.
[0042] FIG. 30 is a somewhat schematic side view of an exemplary
dispenser station configured to be operated automatically, in
accordance with aspects of the present teachings.
[0043] FIG. 31 is a side view of yet another exemplary system for
dispensing biological fluids and including a multi-tiered
arrangement of dispenser stations, in accordance with aspects of
the present teachings.
[0044] FIG. 32 is a three-panel somewhat schematic view of an
exemplary dispenser station with a stock fluid return mechanism, in
accordance with aspects of the present teachings. The figure shows
an initial, predispense configuration (Panel A), an intermediate
configuration (Panel B), and a final, postdispense configuration
(Panel C).
DETAILED DESCRIPTION
[0045] The present teachings provide systems, including methods and
apparatus, for dispensing biological fluids, such as allergen
extracts. The systems may provide dispensers that couple supply
vessels of biological fluids to receiver vessels by engagement with
closures of the vessels, particularly sealed engagement with
elastomeric closures. In some embodiments, the dispensers may
include conduits configured to penetrate the closures of the supply
and receiver vessels. For example, the conduits may be pointed, to
pierce the closures, and the conduits may include an internal bore
through which fluid may flow through the conduit (and closure). The
supply vessels may remain coupled to the dispensers as the
dispensers are operated to transfer the biological fluids to the
receiver vessels. Each receiver vessel may be engaged selectively
with a suitable set of dispensers to select the types and amounts
of biological fluids to be dispensed to the receiver vessel, for
example, to mix a custom set of allergen extracts in the receiver
vessel. The dispensers may be configured to minimize exposure of
the biological fluids to the ambient environment as they are
dispensed, so that the chance of contamination of the fluids is
minimized and the biological fluids remain at least substantially
sterile. Accordingly, the biological fluids dispensed into the
receiver vessels may be suitable for injection into human subjects,
such as allergy patients.
[0046] Further aspects of the present teachings are included in the
following sections, including, among others, (I) overview of
exemplary dispensing systems; (II) vessels; (III) biological
fluids; (IV) dispensers, including (A) conduit structures, (B)
pumps, (C) valves, (D) dispenser housings, and (E) additional
features; (V) housings; (VI) thermal control systems; (VII)
controllers; (VIII) drivers; (IX) methods of operation; and (X)
examples.
I. Overview of Exemplary Dispensing Systems
[0047] This section describes exemplary systems for dispensing
biological fluids, in accordance with aspects of the present
teachings. These systems may include a variety of components,
including supply vessels, dispensers, receiver vessels, and/or
controllers, among others.
[0048] FIG. 2 shows a schematic view of a first exemplary system 54
for dispensing biological fluids. System 54 may include a plurality
of dispenser stations 55 at which supply (e.g., stock) vessels 56
with biological fluids are coupled to dispensers 57. Receiver
vessels 58 may be coupled selectively to the dispenser stations
such that operation of the corresponding dispensers results in
transfer of aliquots of the biological fluids to the receiver
vessels. Further aspects of vessels and biological fluids are
described below, for example, in Sections II and III,
respectively.
[0049] System 54 also may include a thermal control system 59 that
regulates the temperature of the supply vessels and their fluid
contents. For example, the thermal control system may cool (and/or
heat) the supply vessels, shown at 60A, to the same and/or
different temperatures. In some examples, the thermal control
system may be configured to cool (refrigerate) the supply vessels
and/or a compartment(s) in which the supply vessels are disposed,
such that the biological fluids in the supply vessels are
maintained at a temperature below the ambient temperature around
the system. In some examples, the thermal control system also or
alternatively may regulate, indicated at 60B, the temperature in a
compartment around the dispensers.
[0050] System 54 further may include a controller 61. The
controller may, for example, include an input interface 62A (e.g.,
to receiver user inputs or other data, such as scanned or read
data, and/or temperature data from the thermal control system), a
display 62B to output (or input) data related to system 54, and/or
memory 62C to store instructions (e.g., software, hardware, and/or
firmware) for, user preferences about, and/or data produced by,
operation of the system. Further aspects of controllers are
described below, for example, in Section VII.
[0051] In some embodiments, system 54 may include a drive mechanism
(a driver) 63 to drive relative movement within the system. The
driver may be configured, for example, to move the supply vessels,
structures of the dispensers, and/or the receiver vessels, among
others. For example, the driver may be configured to pivotably
and/or translationally move a housing holding the supply vessels
(and/or dispensers), and/or to reposition the supply vessels
(and/or dispensers) relative to an operator of the system and/or a
receiver vessel(s). Alternatively, or in addition, the driver may
drive movement of a receiver vessel(s), such as vertical movement
to engage the receiver vessel with a dispenser (to provide fluid
communication between the dispenser and the receiver vessel) and/or
horizontal movement to align a receiver vessel with a dispenser
and/or dispenser station. Further aspects of drivers are described
elsewhere in the present teachings, such as in Section VIII.
[0052] FIG. 3 shows an exemplary dispenser station 55 of system 54.
Dispenser 57 of the dispenser station may include a fluidics
mechanism 64 that provides fluid transfer from stock vessel 56 to
receiver vessel 58. The dispenser optionally may include one or
more additional features 65.
[0053] Fluidics mechanism 64 may include a conduit structure 66, at
least one pump 67, and at least one valve 68, among others. The
conduit structure may provide a fluid flow path(s) between the
supply vessel and the receiver vessel. In some examples, the
conduit structure may engage closures of the supply and receiver
vessels tightly enough to restrict fluid flow at the site of
engagement between the closures and conduit structure (sealed
engagement) and/or may extend through the closures. Accordingly,
the conduit structure may permit fluid to be transferred between
vessels that remain substantially closed and/or that can re-seal
themselves by removal of the conduit structure (uncoupling the
conduit structure from the vessels). The pump (or pumps) may propel
fluid through the conduit structure and may be used to control
and/or measure the volume of fluid transferred from a supply vessel
to a receiver vessel. The valve (or valves) may regulate flow of
fluid through the conduit structure, for example, to determine the
direction of fluid flow. Further aspects of fluidics mechanisms are
described, for example, in Section IV and in the Examples, among
others.
[0054] Features 65 of the dispenser may be involved in operation,
control, protection, and/or monitoring of the dispenser, among
others. These features may be included in at least one dispenser,
any suitable subset, or all of the dispensers of the system (or may
be absent from the system). Each feature may be present one or more
times in a dispenser, in the same or different forms. In some
examples, a feature may be shared among two or more dispensers (or
all dispensers to provide system features). These features may
include a housing 69, a switch 70, a sensor 71, a driver 72, a data
input mechanism 73, a display 74, a controller 75, and/or a
sterilizer 76, among others. Further aspects of these features are
described elsewhere in the present teachings, such as in Section IV
and in the Examples, among others.
[0055] FIG. 4 shows thermal control system 59 of system 54. The
thermal control system may include at least one controller 77, at
least one heater and/or cooler 78, and/or at least one temperature
sensor 79. In some examples, the controller may be in communication
with at least one heater/cooler and sensor to provide a
feedback-based regulation of temperature within the system. In
particular, the controller may receive a sensed signal(s) from the
sensor and then generate a control signal for the heater/cooler
based on the sensed signal(s). The sensor then may sense any
temperature change produced by operation of the heater/cooler, to
complete the loop. Further aspects of thermal control systems are
described below, for example, in Section VI.
[0056] FIG. 5 shows a schematic view of a second exemplary system
80 for dispensing biological fluids, such as allergens. System 80
may include a housing 82, a plurality of dispenser units 84 coupled
to the housing, and a controller 86 to monitor and/or regulate any
suitable aspects of the system.
[0057] Housing 82 may be configured to hold a plurality of supply
(stock) vessels, such as vessels 88, 90, 92. Each stock vessel may
include a biological fluid, such as fluids 94, 96, 98, generally in
liquid form. The housing may be configured to protect the supply
vessels and their biological fluids from ambient conditions, for
example, by defining an interior compartment(s) that may be cooled,
protected from light, etc. In some examples, the housing may be
coupled movably to a base, so that the housing may reciprocate or
turn, among others, on the base. This movement of the housing may
permit a person dispensing the biological fluids to gain sequential
access to, and/or to conveniently position, different
dispensers/biological fluids.
[0058] Dispenser units (or dispensers) 84 each may be configured to
remain coupled continuously to the housing and to the supply
vessels during dispensing operations and/or when system 80 is idle,
to provide a set of dispenser stations 85. Accordingly, the
dispensers (and the dispenser stations) may be attached to the
housing with fixed relative positions, so that the dispensers are
disposed in a fixed array for more convenient and/or error-free
identification of dispenser stations. The dispensers/dispenser
stations also may be configured to be uncoupled from the housing
(with or without their coupled supply vessels) to permit, for
example, maintenance, replacement, and/or replenishment of
dispensers, supply vessels, and/or biological fluids. The
dispensers may be coupled to a receiver vessel 102 into which one
or more of the biological fluids may be dispensed. The receiver
vessel 102, shown in solid outline, may be coupled to only one
dispenser, or may be coupled in parallel or sequentially to one or
more additional dispensers, shown in phantom outline at 104, to mix
and/or dilute various biological fluids from the supply
vessels.
[0059] Controller 86 may be coupled to the housing, the supply
vessels, and/or the dispensers, among others. The controller may
include one or more sensors 106 to detect one or more aspects of
the system, such as the temperature and/or humidity of an interior
compartment 108 of the housing, information about a supply and/or
receiver vessel, and/or the like. The controller also or
alternatively may include one or more devices for modifying a
condition of the interior compartment, such as a cooling device 110
and/or humidifier/dehumidifier, or the like. The controller further
may be in communication with the dispensers to monitor and/or
regulate aspects of dispenser operation, such as pump operation
(e.g., volume of fluid dispensed from a dispenser).
[0060] FIG. 6 shows a somewhat schematic view of a dispenser
station 85 from system 80. The dispenser station, and particularly
the dispenser unit 84 of the station, may include a pump 132 to
move fluid, and a valve 134 operable to direct and/or restrict
fluid flow through a conduit structure 136 of the dispenser unit.
The conduit structure may provide fluid communication between
supply vessel 88, the pump, the valve, and/or receiver vessel
102.
[0061] In some examples, operation of the valve may place the
dispenser unit in a loading configuration or in a delivery (or
release) configuration. The loading configuration may place the
pump in fluid communication with biological fluid 94 of supply
vessel 88, for loading a measured volume of the biological fluid
into the pump. The supply vessel also may include or be coupled to
a vent 138 that restricts formation of a negative pressure in the
supply vessel during loading. In some examples, the vent may be
provided by part of the conduit structure itself (e.g., the
Examples). The delivery configuration may place the pump in fluid
communication with an outlet 140 that may be coupled to receiver
vessel 102, for delivering a measured volume of fluid to the
receiver vessel with the pump. (The volume loaded into the pump may
be the same as, or different from, the volume delivered from the
pump.) The pump and/or the valve may be operated and/or actuated
manually and/or automatically. In some examples, the valve may be
operated (and/or adjusted) by moving the pump between a loading
configuration and a release configuration. In other examples, the
valve further may be operated (and/or adjusted) by moving the pump
between additional configurations, such as two or more loading
configurations, two or more release configurations, holding
configurations, and so on.
[0062] FIG. 7 shows another exemplary dispenser station 150
including a dispenser 152 coupling a supply vessel 154 to a
receiver vessel 156. Dispenser 152 may include a fluidics mechanism
158 having a conduit structure 160, a pump 162, and one or more
valves 164, 166.
[0063] Conduit structure 160 may remain coupled to the supply
vessel as the receiver vessel is coupled to and uncoupled from the
fluidics mechanism, such that a fluid aliquot can be transferred
from the supply vessel to the receiver vessel without disengagement
of the dispenser from the supply vessel. End regions or conduits
168, 169 of the conduit structure may be configured to pierce
closures 170, 171 of the vessels.
[0064] Valves 164, 166 (or one valve) may be adjustable to direct
fluid flow in the conduit structure. For example, the valves may be
adjustable to provide selective fluid communication between the
pump and the supply vessel, such that a loading pathway 172 is open
and a delivery pathway 174 is closed. The valves also may be
adjustable to provide selective fluid communication between the
pump and the receiver vessel, such that the loading pathway is
closed and the delivery pathway is open. In some examples, this
adjustable fluid communication may operate to restrict reverse flow
of fluid in the system, that is, to restrict flow of fluid from the
receiver vessel to the supply vessel, from the receiver vessel to
the pump, and/or from the pump to the supply vessel, among others.
Restricting reverse flow of fluid may, for example, reduce
contamination of the supply vessel and/or conduit structure and/or
may provide better operation of the pump. The valves may be
adjustable by any suitable mechanism, including movement of the
pump (all or a portion of the pump), operation of the pump, manual
actuation of a switch (directly or indirectly by an operator),
automatic actuation of a switch, and/or the like.
[0065] The systems provided herein may have a number of advantages
for dispensing biological fluids, particularly forming mixtures of
allergens for immunotherapy. The advantages may include one or more
of the following, among others: (1) reduced light-mediated
degradation of biological fluids, (2) reduced temperature-mediated
degradation of biological fluids, (3) increased speed of dispensing
to form mixtures, (4) decreased labor costs, (4) fewer punctures of
stock vessels (through their closures) and thus a reduced number of
closure-derived plugs in the biological fluids, (5) improved
longevity and consistency of biological fluids, (6) improved
organization of stock biological fluids in an array, (7) reduced
chance of needle sticks, (8) reduced repetitive finger injuries,
(9) decreased chance of errors in dispensing, (10) reduced chance
of replacing syringe needle in wrong stock vessel, (11) reduced
repetitive sterilization of closures of stock and receiver vessels
(and associated chance of sample contamination and/or degradation),
(12) reduced set-up time, (13) easier replacement of stock vessels
when depleted, (14) higher speed without the expense and
maintenance costs of a high technology system, (15) parts may be
disposable, (16) decreased syringe usage, (17) vented with reduced
vacuum, less denaturation, and fewer air bubbles than would be
produced typically by fast movement of fluid through needles, (18)
quicker and/or more efficient addition of diluent, (19) definite
procedure for loading, checking, and delivering to increase
accuracy, (20) reduced need for bacteriostatic lights (which may
denature allergens), (21) reduced chance of contamination, (22)
less chance of undesired direct contact between fluids in stock and
receiver vessels, (23) manual operation that is easy to learn,
and/or (24) reduced condensation and thus fewer problems with
labels coming off vessels.
II. Vessels
[0066] The dispensing systems described herein may be configured to
be used with vessels for holding biological fluids. The vessels may
have any suitable size, shape, composition, closure, and/or
coupling structure, among others.
[0067] The size of each vessel may be selected, for example,
according to the volume of biological fluid(s) to be held in the
vessel, the capacity of the pump, and/or the volumes to be
dispensed, among others. Accordingly, supply vessels may be large
enough to hold one dispensed volume or a plurality of dispensed
volumes. In some examples, the supply vessels may be large enough
to hold many dispensed volumes, such as about 10, 100, or 1,000
dispensed volumes, among others. In some examples, each dispensed
volume may be about 0.1 to 1.0 milliliters and a supply vessel may
have a capacity of about 10 to 100 milliliters of fluid. In other
examples, the supply vessel may have a capacity of about 0.1 to
10,000 milliliters. Similarly, receiver vessels may be large enough
to hold at least one dispensed volume or a plurality of dispensed
volumes, with or without added diluent. Receiver vessels thus may
be similar in size to supply vessels, or larger or smaller than the
receiver vessels. In some examples, a receiver vessel may have a
capacity of about 5 to 25 milliliters. In other examples, the
receiver vessel may have a capacity of about 0.1 to 1000
milliliters.
[0068] The vessels may be shaped according to their intended
purposes. The vessels may be generally cylindrical, frustoconical,
spherical, cubical, polyhedral, and/or the like. The vessels may
have flat bottoms, to support the vessels on a flat surface. The
vessels may have a varying diameter, for example, narrowing near
the top of the vessels, to provide a neck that defines the mouth of
the vessels.
[0069] The vessels may be formed of a material that is generally
inert to the biological fluids. Exemplary materials may include
glass (e.g., borosilicate glass), plastic, and/or metal, among
others. The material may be at least partially transparent or may
be opaque. The material may be colorless, or may be colored, for
example, darkened or tinted to restrict entry of light.
[0070] The vessels may include coupling structures to permit
conduits to be coupled to the vessels. The coupling structures may
be included in closures, and/or may be distinct from the closures.
The coupling structures may permit conduits to be placed in fluid
communication with the vessels in a sealed relationship, so that
fluid can pass through the conduits from and/or to vessels, but
generally is restricted from passing between the exterior of the
conduit and vessels.
[0071] The vessels may have elastomeric/resilient closures, such as
septa, to seal the vessels and thus restrict fluid passage from/to
the vessels. A closure may be any structure that at least
substantially restricts passage of fluid, and particularly a
liquid, into and/or out of a vessel. In some examples, the closure
may hermetically seal the vessel, at least prior to coupling the
vessel to a dispenser. The closures may include plugs, septa, caps,
lids, and/or the like. Closures may be secured to vessels by
threadable engagement, an interference fit, a clip or retainer, a
resilient flange, and/or the like.
[0072] In some examples, the closures may be configured to receive
a conduit. The closures may be penetrated and/or pierced by hollow
conduits, such as hollow needles, to permit fluid movement from/to
the vessels, for example, to remove and/or add a volume of
biological fluid to/from the vessels and/or to function as a vent
during and/or after this movement. A resiliency and/or elasticity
of the closures may provide a seal around the conduits after the
closures are penetrated by the conduits and/or may seal the
closures after the conduits are removed from the closures. The seal
between a conduit and a closure may substantially restrict fluid
flow at the seal. However, in some examples, the seal also may
permit limited movement of gas around the conduit, to relieve a
pressure differential between the inside and outside of the vessel
(see Example 2).
[0073] In exemplary embodiments, the vessels may be vials. A vial,
as used herein, is a vessel for holding relatively small amounts of
fluid. In exemplary embodiments, a vial may hold less than or equal
to about 500 milliliters or 100 milliliters of fluid, among
others.
III. Biological Fluids
[0074] The dispensing systems described herein may be configured to
be used for transfer of biological fluids between vessels,
particularly for forming predefined mixtures of the biological
fluids in vessels.
[0075] The biological fluids generally include any fluid--liquid
and/or gas--at least partially derived from and/or affecting living
organisms. The biological fluids may include any suitable ratios of
biological extracts, synthetic compounds, microorganisms,
organelles, excipients, diluents, buffers, salts, and/or the like.
The biological fluids also may include markers, such as dyes and/or
other (preferably biologically inert) compounds, to identify the
fluid and/or to indicate addition or removal of fluids during
sample preparation. The biological fluids may be aqueous, or
predominantly aqueous, having water as a major component. However,
in some cases, the fluids may be organic, having an organic solvent
(particularly a biologically compatible organic solvent such as
DMSO or DMF) as a major component. Alternatively, or in addition,
the biological fluids may include trace amounts of organic
solvents, such as DMSO or DMF, particularly if used as a carrier
for another component.
[0076] The biological fluids may be used for any suitable purpose.
For example, each biological fluid may be a preparation, such as a
drug, a vaccine (an antigen), or an antitoxin, used medically as a
diagnostic, preventive, and/or therapeutic agent. The preparation
may be at least partially synthesized by living organisms or their
products, and/or may be based structurally on a material produced
by a living organism. Exemplary biologically active agents in
biological fluids may include proteins, peptides, nucleic acids,
carbohydrates, vitamins, metal ions, lipids, hormones, etc. More
specifically, exemplary biologically active agents may include
allergens, such as extracts (particularly protein extracts) from
food, molds, animal dander, plants, pollens, dust mites, venoms,
bacteria, and/or the like. In some examples, the biological fluids
may include synthetic allergens, for example, synthetic peptides.
Exemplary biologically active agents also may include research,
diagnostic, and/or clinical materials obtained via any suitable
mechanism (e.g., excisions, aspirations, swipes, swabs,
phlebotomies, etc.) from biopsies and/or necropsies of cells,
tissues, and/or biological fluids (e.g., saliva, blood, urine,
lymph, mucous, semen, etc.), among others.
[0077] The biologically active agents may be present at any
suitable concentration. Accordingly, in some examples, the
biological fluids may include different dilutions of a biologically
active agent, such as serial two-fold or ten-fold dilutions, among
others. Alternatively, or in addition, the biological fluids may
include repetitions of the same fluid (i.e., two or more stations
having the same fluid), particularly commonly used fluids.
[0078] The biologically active agents may be present in any
suitable amount(s), in any suitable state(s). The amounts may be
measured by concentration, for example, picomolar, nanomolar,
micromolar, millimolar, and molar. Alternatively, or in addition,
the amounts may be measured in effective amounts, for example,
effective to induce or desensitize an immune response, effective to
bring about a desired therapeutic response, effective to diagnose a
condition, and so on. The suitable states may include solutions,
suspensions, emulsions, dispersions (including colloidal
dispersions), gels, aerosols, and so on, and/or mixtures
thereof.
IV. Dispensers
[0079] The dispensing systems described herein may include one or
more dispenser stations at which biological fluids may be
dispensed. Each dispenser station may include a dispenser
configured for manual and/or automatic operation. The dispenser may
include conduit structure that provides a sealed coupling with a
supply vessel, a receiver vessel, and/or between the supply and
receiver vessels. The dispenser also may include at least one pump
and/or at least one valve configured to move fluid through the
conduit structure and/or direct and/or regulate this fluid
movement.
[0080] The dispenser stations and/or their dispensers may have any
suitable arrangement in a dispensing system. In some cases, the
dispenser station at a given position may be missing, replaced with
a nonfunctional blank, or replaced with a solid dispenser (e.g., to
dispense easily soluble materials such as salts for use in
preparing buffers). In the same or other cases, dispensers
designated for and/or containing biological fluids related by some
common characteristic (e.g., type (e.g., grass allergen, tree
allergen, etc.), concentration (e.g., low concentration, high
concentration, etc.), and so on) may be organized relative to one
another according to some predefined criteria or rule. For example,
biological fluids that commonly would be dispensed into a common
receiving vessel may be positioned adjacent one another to enhance
the speed and convenience of dispensing, and biological fluids that
less commonly would be dispensed together, or that should not be
dispensed together, may be positioned far from one another to
reduce the possibility that they will be co-dispensed.
[0081] A. Conduit Structures
[0082] The dispensers each may include a conduit structure that
provides fluid communication between the valve, pump, supply
vessel, and/or receiver vessel. The conduit structure may include
any suitable mechanism for routing fluid, such as rigid tubes,
flexible tubing, pipes, channels, bores, manifolds, and/or the
like.
[0083] The conduit structure may include any suitable number of
conduits connected by any suitable connector mechanisms. Exemplary
mechanisms for connecting conduits to each other and/or to a valve
and/or a pump within a dispenser may be reversible or
non-reversible, including connections that are Luer-Lok, snap-fit,
interference fit, clamped, threaded, bonded, adhesive, welded,
and/or the like. In some examples, one or more of the conduits or
other dispenser components may be sealed adjacent an opening with a
swabbable valve that remains closed until the conduit or component
is connected to another conduit or component.
[0084] Coupling conduits generally include any structures at which
biological fluids can be transferred from a supply vessel to a
dispenser (an inlet conduit) and/or from a dispenser to a receiver
vessel (an outlet conduit). The coupling conduits thus may include
a conduit or conduit region having a tip into and/or from which
biological fluids can enter or exit a dispenser. The tip may be
blunt or sharp (such as a hollow-bore needle). Coupling conduits
alternatively or in addition may include coupling structure with
which these conduits may be coupled to a supply or receiver vessel,
such as a plug, cap, and/or the like, attached to the coupling
conduit and configured for engagement with the supply or receiver
vessel. This plug or cap may be sealed circumferentially around the
coupling conduit to restrict fluid leakage. Alternatively, the
coupling conduit itself may engage the supply or receiver vessel so
that the conduit is sealed against the vessel, such as by
penetration of a closure of the supply or receiver vessel, or the
coupling conduit may deliver biological fluids in a nonsealed
relation with the receiver vessel (such as through an open mouth of
this vessel). An outlet conduit may be configured for contact
and/or noncontact dispensing, in which the outlet conduit contacts
or does not contact the receiving fluid or container as part of the
dispensing process, respectively. The coupling cap or attachment to
the supply vessel may be designed as a one-way insertion device,
clamping and/or sealing the supply vessel in place. In addition,
the coupling cap or attachment to the supply vessel may be designed
as a break-away connection if the supply vessel is removed before
it is completely emptied to prevent unauthorized use of the
dispensing system, e.g., the supply vessel is returned to storage
or removed for another purpose from the coupling conduit.
[0085] B. Pumps
[0086] Pumps generally include any device for actively moving
biological fluids within the dispensers. Such active movement may
be effected by pushing and/or pulling and/or otherwise biasing
fluid to and/or from the pumps. The active movement may be
effected, for example, by directly pushing on the fluid, for
example, by a piston, a vane, pressurized gas, and/or a spring,
among others.
[0087] Pumps used for dispensing may be any suitable manually
operated or automated pumps. A manually operated pump may be driven
by direct engagement of an operator with the pump, such as
engagement of a syringe piston (plunger) with a hand(s), and/or
engagement with a pump coupled structure, such as a mechanical
assist mechanism, among others (e.g., see Example 5). Automated
pumps may include a motor, such as an electric motor, that drives
the pumps. Motor-driven pumps may include a driver or motor that is
controlled manually, such as by having a user manipulate a pump
control (such as a switch), and/or automatically, such as with a
controller (e.g., see Example 6).
[0088] The pumps may be of any suitable type including
positive-displacement and/or dynamic pumps, among others.
Positive-displacement pumps may move fluid by filling a cavity and
then displacing a given volume of the fluid. Exemplary
positive-displacement pumps may include piston, bellows,
double-diaphragm, flexible impeller, gear, oscillating, progressing
cavity, rotary, linear, and/or peristaltic pumps, among others.
Dynamic pumps may move fluid by increasing its speed or velocity.
Exemplary dynamic pumps may include centrifugal pumps.
[0089] The pumps may be configured to move measured volumes of
fluid, for example, based on the number of pump strokes/cycles
performed, and/or based on the size of a partial stroke/cycle of a
pump, among others. Any suitable volume may be measured and moved
by a pump. A volume transferred by a pump may be selected during
operation of the pump, such as during manual operation of a syringe
pump, and/or may be selected before pump operation, such as through
input of volume data to the controller of an automated pump system.
Input may be via any suitable interface such as a keyboard,
touchscreen, mouse, joy stick, touch screen, dial, lever,
button(s), network connection, etc. (e.g. see Example 6). The
interface may be a dedicated interface for an individual dispenser
or subset of dispensers (such as the dispensers on a side of the
dispensing system), and/or may be an interface for inputting volume
data for all of the dispensers.
[0090] Operation of the pump may be detected by one or more
sensors. The sensor may sense any suitable aspect or result of pump
operation, such as plunger position and/or range of motion, motion
of a motor driving the pump, pressure produced, fluid flow rate,
and/or the like. Accordingly, the sensor may allow a controller to
monitor, verify, and/or record pump operation and/or a volume
dispensed to a receiver vessel, among others. Exemplary sensors may
include rotary encoders, linear encoders, piezoelectric sensors,
heat conduction sensors, and/or the like. Further aspects of using
sensors to measure pump operation are described elsewhere in the
present teachings, such as Section VII and Examples 5 and 6, among
others
[0091] Exemplary pumps may include manually-driven or power-driven
syringe pumps. The syringe pumps may have any suitable barrel
capacity, such as a capacity of about 0.1 to 10 milliliters, among
others. In some examples, a dispensing system may include syringes
of different capacities coupled to different dispensers, such as
smaller capacity syringes for dispensing allergens and larger
capacity syringes for dispensing excipients/diluents. In exemplary
embodiments, some or all of the syringe pumps may have a capacity
of about one milliliter. Graduations or other indicia on the
syringe pumps may be used to set and/or permit visual measurement
of loaded/delivered fluid volumes.
[0092] C. Valves
[0093] Valves generally include any device for controlling the
velocity (including the starting and stopping) and/or direction of
flow of biological fluids within the dispensers. The valves may be
controlled manually, with or without-driven assistance (such as a
solenoid operated by a switch), and/or automatically (such as with
an electronic controller and a solenoid). Exemplary valves may
include angle, ball, butterfly, check (to restrict reverse flow),
diaphragm, flipper, gate, globe, needle, pinch, slide, and/or stop
cock valves, among others. Exemplary valves alternatively and/or in
addition may include two-way, three-way, four-way, and/or
higher-order way valves, capable of receiving and/or directing
fluid from any suitable or desired directions, and/or numbers of
directions.
[0094] In some embodiments, the valve(s) of a dispenser may be
controlled, operated, and/or adjusted by movement of a pump. The
pump movement may be driven manually (that is, by hand) and/or with
a motor. The movement may be pivotal (e.g., see Examples 1 and 5)
and/or translational (e.g., to operate a slide valve). Furthermore,
the movement may involve the entire pump (see Examples 1 and 5) or
a component of the pump (e.g., operation of check valves (see
Example 2)). If a component of the pump is involved, the direction,
extent, and/or rate of movement may determine how the valve(s) are
controlled, operated and/or adjusted.
[0095] D. Dispenser Housings
[0096] The dispensers also may include a dispenser housing in which
(and/or to which) a conduit structure, a pump, a valve, and/or an
outlet may be at least partially disposed (and/or connected). The
dispenser housing may include coupling structure that permits
attachment of the dispenser to the dispensing system. The dispenser
housing also may have a number of other functions (such as
guiding/restricting operation of the pump and/or valve; protection
of the conduit structure, pump, and/or valve, from contamination,
damage, inadvertent uncoupling, etc.; and/or providing a site for
sterilization; among others). Accordingly, the dispenser housing
may include any suitable number of openings to permit access to the
conduit structure (particularly the outlet and/or inlet conduits),
pump, and/or valve, and/or to permit conduits and/or conduit
regions to extend from the dispenser housing. The dispenser housing
also may support a supply vessel, for example, by receiving the
supply vessel in an opening defined by the dispenser housing.
[0097] The dispenser housing may define any suitable compartment.
In some examples, the compartment may be substantially enclosed. In
any case, the dispensing system may be configured to impart a
positive pressure to the compartment using treated air (e.g.,
filtered air from a blower unit; see Example 3). Furthermore, the
temperature of the air may be controlled or modified (e.g., cooled)
to control or modify the temperature of the compartment.
[0098] E. Additional Features
[0099] Each dispenser may include one or more additional features
such as at least one switch, sensor, driver, data input mechanism,
display, controller, sterilizer, and/or indicia, among others.
[0100] The switch may include any mechanism for selecting a
configuration and/or operating condition of a dispenser. The switch
may be actuated manually (operated by hand or any part of the human
body (such as a foot)) and/or automatically (not manually). The
switch thus may be mechanical, electrical, optical, piezoelectric,
and/or the like. The switch may control the operation and/or
configuration of any suitable dispenser mechanism, such as a
pump(s), valve(s), sensor, driver, data input mechanism, display,
controller, and/or sterilizer, among others. Further aspects of
switches are described elsewhere in the present teachings, such as
in the Examples 1, 2, and 4-6, among others.
[0101] The sensor may include any mechanism for sensing an aspect
of a dispenser. The aspect may be related to pump operation, valve
position, fluid flow rate, temperature, etc. Further aspects of
sensors are described elsewhere in the present teachings, such as
in Section VI and in Examples 5 and 6, among others.
[0102] Drivers, data input mechanisms, displays, controllers, and
sterilizers are described elsewhere in the present teachings.
Drivers, data input mechanisms, and displays are described, for
example, in Section VII and Example 6, among others. A controller
may be a system controller or a dispenser controller dedicated to a
particular dispenser, among others. Controllers are described, for
example, in Section VII and Examples 5 and 6, among others.
Sterilizers are described, for example, in Example 4, among
others.
[0103] The dispenser housing, another portion of the dispenser
station, and/or the associated system housing may include indicia
that identifies the biological fluid dispensed by the dispenser
station. The indicia may include one or more alphanumeric
characters (such as letters, words, and/or numbers), symbols,
pictures, a color code, a bar code, an electronic code (such as
data on a readable electronic chip (e.g., a Radiofrequency
Identification (RFID) tag), and/or the like. These indicia may be
used to verify and/or track the type of material (biological
material) associated with the dispenser, before and/or after
dispensing. In some cases, the indicia may be removable (such as
one or more preprinted or custom printed stickers) and/or
scannable/readable (such as by an optical or radiofrequency reader)
to facilitate compiling a record of dispensed materials.
V. Housings
[0104] The dispensing systems described herein may include one or
more housings to hold dispenser stations and their supply vessels.
Each housing may protect the supply vessels from ambient conditions
and/or may organize and/or adjustably position the dispenser
stations (and/or their supply vessels and/or dispensers), among
others.
[0105] The housing may have suitable size and shape. The housing
may be large enough to hold any suitable number of dispensers and
supply vessels. Portions of the dispensers (such as the housings,
pumps, valves, and/or outlets) may be disposed substantially
outside (or substantially inside) the housing. The housing may hold
the supply vessels substantially (or completely) in an interior
compartment(s) defined by the housing. The interior compartment may
be a chamber (or chambers) that can be substantially closed to the
outside. The housing may be generally circular (or cylindrical),
polygonal, and/or the like.
[0106] The housing may define a plurality of openings to receive
supply vessels. At least a subset of the openings may be configured
to receive supply vessels, conduits, and/or portions of the
dispensers. The openings may be configured to receive the supply
vessels from below, above, and/or from the side(s) of the housing.
The openings may be disposed adjacent the side walls of the
housing, so that the supply vessels and dispensers are positioned
around a central axis of the housing. Alternatively, or in
addition, the openings may be disposed in one row or in a plurality
of generally parallel rows. In some examples, openings of the
housing that are not in use may be covered with a plug or a cap,
among others, to restrict air flow through these openings. In some
examples, one or more openings of the housing may be configured to
receive a cooling device, electrical or fluid conduits, and/or the
like.
[0107] The housing may be connected to a support structure (a base)
that supports the housing. The base may have any suitable height,
such a relatively taller base to provide a floor-supported system,
and/or a relatively shorter base to provide a table-top system,
among others. The housing may be fixed or movable relative to the
support structure. A fixed housing may be mounted fixedly on the
support structure, for example, a housing with legs affixed to the
housing. A movable housing may be coupled to a support structure so
that the housing and its connected dispensers can be moved in
relation to the support structure and in relation to an operator of
the dispensers. The housing may move rotationally (e.g., turn)
and/or translationally (e.g., slide). Translational movement may
include linear reciprocation and/or orthogonal movement, among
others. In some examples, only a portion of the housing may be
movable, such as a portion connected to a subset (or all) of the
dispensers.
[0108] The housing may be formed of a set of sub-housings each
configured to hold a plurality of supply vessels. In some examples,
the sub-housings may be removable modules that can be added to, or
removed from, the system, to increase or decrease the number of
supply vessels that can be received by the combined system housing.
The sub-housings may be configured to be fixed or movable in
relation to one another. If movable, the sub-housings may be
configured to move translationally (e.g., horizontally and/or
vertically) and/or pivotably in relation to one another. In some
embodiments, the sub-housings may share the same pivot axis. The
sub-housings may be arranged vertically (e.g., stacked) and/or
horizontally relative to one another. The sub-housings may have the
same size or different sizes. For examples, the sub-housings may be
stacked vertically, with each sub-housing down the stack having a
decreased diameter relative to the sub-housing above it. Further
aspects housings with movable sub-housings are described elsewhere
in the in the present teachings, such as in Example 7.
[0109] The housing may have any suitable composition. In some
examples, the housing may be formed at least partially of a
substantially transparent material, so that the interior
compartment(s) of the housing and its contents may be examined
visually from external the housing. In some examples, the side
walls of the housing may be transparent. In some examples, the
housing may be configured to restrict entry of light into the
housing. Accordingly, the housing may include one or more
transparent, colored or darkened walls, and/or one or more opaque
walls. These materials may be selected according to any suitable
criteria, e.g., to be biologically inert, easy to clean, difficult
to break, and so on.
VI. Thermal Control Systems
[0110] The dispensing system may include a thermal control system
to regulate temperature within the system. The thermal control
system may regulate the temperature of any suitable components of
the system including supply vessels, dispensers, receiver vessels,
the housing, and/or regions thereof.
[0111] The thermal control system may include a cooling and/or
heating device(s) and a heat (temperature) sensor(s), among others.
The cooling/heating devices and sensors may be present at any
suitable ratio. For example, the system may include the same or a
different number of cooling/heating devices and sensors. In some
examples, the system may include sets of one or more
cooling/heating devices and one or more sensors that function
together to provide individual temperature control for thermally
isolated regions of the system.
[0112] The cooling and/or heating device(s) may operate by any
suitable conductive, convective, and/or radiative mechanism.
Exemplary cooling and/or heating devices may include peltier
devices, resistive heating elements, fans, condensers, compressors,
coolers based on water flow, lamps, etc.
[0113] The temperature sensor (or sensors) may have any suitable
structure and may be a contact or noncontact device. Exemplary
temperature sensors may include thermocouples, thermistors,
resistance temperature devices, radiation thermometers
(pyrometers), thermal imagers, (liquid in glass) thermometers,
and/or the like.
[0114] In some examples, the dispensing system may include a
thermoelectric cooling device that operates according to the
peltier effect. Such a thermoelectric cooling device may reduce
condensation while refrigerating an interior compartment(s) of the
housing holding one or more supply vessels, thereby minimizing
damage to, and/or detachment of, labels, and/or growth of
microorganisms, among others.
VII. Controllers
[0115] The dispensing systems described herein may include one or
more controllers. Each controller may be configured to monitor
and/or control aspects of operation of a dispensing system.
[0116] The controller may include digital instructions and
processing capabilities. For example, the controller may include a
processor to perform data manipulation. The controller also or
alternatively may include a memory to store instructions that may
be used by the processor and/or to store other data received or
generated by the controller.
[0117] The controller may include any suitable input (and/or
output) interface(s) for receiving (and/or outputting) data.
Exemplary input (and/or output) interfaces may include a user
interface, a network connection, a port for removable storage
media, a sensor interface, a reader interface, a printer interface,
and/or the like.
[0118] The user interface (such as a mouse, joystick, keyboard,
keypad, buttons, switches, touchscreen, etc.) may permit a user to
input data, such as instructions, formulas for mixtures to be
created, and/or preferences for dispensing. The user interface
alternatively or additionally may include a screen, one or more
indicator lights, etc., to output instructions, progress
indicators, and/or data, among others, to the user, such as a
record of dispensing operations, status reports, warnings, etc.
[0119] The sensor interface may provide communication with any
suitable sensor(s). The controller may be in communication with one
or more sensors configured to sense any suitable aspects of a
dispensing system. Such aspects may include temperature, light
intensity, humidity, gas composition, position of the housing,
fluid levels in supply vessels, pump positions, valve positions,
and/or the like. Such aspects also may include the types and/or
volumes of fluids dispensed, the timing and/or order of the
dispensing, and so on. The controller may store, display, and/or
otherwise output data about sensed aspects, for example, to
maintain a record of the sample and sample preparation.
[0120] In some examples, the sensor interface may place the
controller in communication with one or more temperature sensors of
the system. Accordingly, the controller may be configured to
receive and/or store temperature data provided by the sensor(s), so
that the controller can monitor one or more temperatures within the
system (e.g., regulated with distinct thermal, control units (see
Example 2)). The controller thus may be configured to provide a
temperature control record, to document temperature stability
and/or to detect any variations in the regulated temperature over
time. In some examples, the biological fluids may be temperature
sensitive such that temperature stability during their storage may
be important. Accordingly, a temperature control record stored by
the controller may provide a quality assurance for biological
fluids stored in the system house, may facilitate identification of
biological fluids that should be replaced due to lack of
temperature stability in the system, and/or may signal a technical
problem in the thermal control system, among others.
[0121] In some embodiments, the sensor interface may provide
communication with a pump sensor, to monitor and/or provide
feedback about pump operation (e.g., see Example 5).
[0122] The reader interface may provide communication with any
suitable type of reader, such as an optical reader (e.g., a barcode
scanner), a radiofrequency reader (e.g., a Radiofrequency
IDentification (RFID) tag reader), and/or the like. The reader
interface may be suitable, for example, to identify and track a
receiver vessel (with a barcode or RFID tag) before, during, and/or
after dispensing to the receiver vessel, to input data about a
supply vessel, to track inventory, to record lot numbers, and/or
the like.
[0123] The controller may be configured to provide any suitable
information processing capabilities. For example, the controller
may provide automatic computation of an immunizing dose for a human
subject. The computation may be based on data about the subject's
immunization history data that is accessible to the controller.
Alternatively, or in addition, the controller may provide automatic
computation of a suitable extract formula (e.g., types and ratios
of extracts) for an immunotherapy patient based on test (e.g., skin
or RAST) data from the patient. In some embodiments, the controller
may be configured to provide an operator of the dispensing system
with information regarding an inputted extract formula, such as
incompatibilities between extracts, total glycerin concentration in
the mixture, redundant antigens that could be eliminated, cost,
outdate times, etc.
VIII. Drivers
[0124] The dispensing system may include one or more drive
mechanisms (drivers) to guide and control movement within the
system. The drive mechanism may include one or more motors and a
mechanical linkage that couples operation of the motor(s) to
movement of a load. The load may be the system housing, a
sub-housing within the housing, one or more receiver vessels, one
or more supply vessels, the dispenser and/or a component thereof,
and/or the like.
[0125] Any suitable motor(s) may be used in the drive mechanism.
Each motor may be an AC or DC motor, or may be air-powered, among
others. Exemplary motors may be single or multiphase, induction,
servo, synchronous, universal, and/or gear motors. The motor may
rotary or linear. In exemplary embodiments, the motor may be a
stepper motor.
[0126] The drive mechanism may employ any suitable linkage to the
load. Exemplary linkages may include a belt(s), a chain(s), a
gear(s), a screw(s) (e.g. a worm gear), a cable(s), a pulley(s), a
rod(s), rack and pinion, and/or the like. The linkage also may
include a guide structure or track that directs and/or facilitates
sliding movement of the load. Accordingly, the guide structure or
track may include bearings or other elements that promote
sliding.
IX. Methods of Operation
[0127] The dispensing systems described herein may be suitable for
performing methods of dispensing biological fluids, particularly to
form mixtures of the fluids. In some examples, the biological
fluids may be allergens, that is, allergen extracts or synthetic
allergen compounds at any suitable dilution. The methods may
include any suitable combination of the following steps, or other
steps, performed any suitable number of times, in any combination,
and in any suitable order. These steps may be planned and selected
before and/or during dispensing. In some cases, the steps
(including the types and/or amounts of fluids dispensed) may be
determined by stand-alone and/or associated software. Such
software-determined steps may be provided in any suitable format,
such as a printout, a series of software prompts, and so on.
[0128] A single biological fluid or a mixture of biological fluids
to be prepared may be identified or selected. In some examples, the
mixture may be defined based on allergen sensitivity testing.
Identification or selection of the mixture may identify or select a
set of biological fluids to be included in the mixture and
volumes/dilutions/concentrations for each fluid of the set (or for
a single fluid). This step of identification or selection also may
select a volume(s) of diluent(s) and/or excipient(s) to be included
in the mixture (or to be combined with the single biological
fluid). In some embodiments, the step of identification or
selection may be performed by a controller of a dispensing system.
For example, the controller may receive data corresponding to the
types and volumes of fluids to be dispensed to create a mixture,
such as through a user interface and/or other data transfer
mechanism (a network, removable storage media, etc.). In some
examples, the controller may determine a suitable mixture of
allergens for a subject using an algorithm and test data (such as
data from a skin or RAST test) from the subject.
[0129] A dispensing apparatus may be selected and readied for
operation. In particular, supply vessels holding the biological
fluids of the set (and, optionally, supply vessels holding other
biological fluid that are not in the set) may be connected to
dispensers of the dispensing apparatus. The supply vessels may be
disposed in a refrigerated compartment of the dispensing apparatus
and/or may be protected from light.
[0130] One of the fluids of the set may be selected. Selection may
include a step of moving a dispenser (connected to a supply vessel
holding the fluid selected), so that the dispenser is more
conveniently positioned relative to a person operating the
dispensing apparatus. The step of moving may include turning,
and/or inducing translational motion of, a housing to which the
dispenser is connected.
[0131] A measured volume of the selected fluid may be transferred
from its supply vessel to a receiver vessel. The step of
transferring may be performed by passing a portion of the selected
fluid through a closure of the supply vessel and/or the receiver
vessel, and may be performed with the supply vessel continuously
connected to its dispenser. Accordingly, the step of transferring
may be performed as the measured volume remains within a
substantially closed environment, under relatively sterile
conditions. Transfer of the measured volume may be monitored
automatically by a controller coupled to a sensor to provide
feedback to an operator or other interested parties about the
accuracy of manual transfer by the operator. Accordingly, automated
monitoring of manual dispensing may reduce errors, may provide
verification that a mixture was prepared correctly, and/or may
document the size of deviations in volumes dispensed from
predefined target volumes.
[0132] The step of transferring may include a step of loading a
pump with a biological fluid and a step of delivering the
biological fluid from the pump to a receiver vessel. In some
examples, the step of loading a pump may be performed by placing
the pump in fluid communication with a supply vessel connected to
the pump, and then operating the pump to draw a portion of the
fluid into the pump. The pump may be used to load a predefined
volume that is substantially delivered to the receiver vessel.
Alternatively, the pump may be used to load a volume that is larger
than the volume delivered to the receiver vessel, so that only a
portion of the loaded volume is delivered. In some examples, the
step of delivering the biological fluid may include a step of
placing the pump in fluid communication with a receiver vessel
and/or a step of operating the pump to release biological fluid to
the receiver vessel. In each case, the step of placing the pump
and/or the step of operating the pump may be performed manually or
automatically.
[0133] Additional biological fluids of the set may also be selected
and transferred. Transfer with different dispensers to the same
receiver vessel may be performed at different times (generally,
sequentially) or at the same time (for example, by providing two or
more outlets with tubing long enough to reach the receiver vessel
at the same time).
[0134] A biological fluid and/or a mixture of biological fluids
dispensed to a receiver vessel may be injected, after dispensing,
into a human subject, such as an allergy patient. Accordingly the
fluid and/or mixture may be dispensed under conditions that
minimize contamination with microorganisms. Generally, the
biological fluids, the supply vessels, the receiver vessels, and
the fluidic mechanism of each dispenser and/or components thereof
thus may be supplied in a sterile condition, for example, supplied
in a package that has been sterilized. Alternatively, the vials,
the fluidics mechanism, and/or components of the fluidics mechanism
may be supplied with interior compartments sterilized (and exterior
surfaces nonsterile). In any case, the vials and fluidics mechanism
of each dispenser station may be supplied in a sterile condition
internally.
X. EXAMPLES
[0135] The following examples describe selected aspects and
embodiments of the present teachings, including exemplary
dispensing systems and components thereof. These examples and the
various features and aspects thereof are included for illustration
and are not intended to define or limit the entire scope of the
present teachings.
Example 1
Dispensing System I
[0136] This example describes a first exemplary dispensing system
for creating an allergen mixture for immunotherapy by transferring
measured volumes of allergen stocks from stock vials to a patient's
vial; see FIGS. 8-18.
[0137] FIG. 8 show an exemplary system 180 for preparing mixtures
of allergens and/or other biological fluids. The system may include
a housing 182, a base 184, and a plurality of dispenser stations
186, among others.
[0138] The housing 182 may be coupled pivotably to a base 184 so
that the housing can turn around pivot axis 188. Accordingly, the
housing may function as a carousel to provide adjustable access to
allergen stocks 190 disposed in an interior compartment 192 defined
by the walls of the housing. The base may include legs 194 mounted
on, and extending upwardly from, a platform 196.
[0139] The housing may include any suitable structure. For example,
the housing may include a bottom wall 198, a top wall 200, and a
plurality of side walls 202 extending between the bottom and top
walls. The bottom and top walls may be opaque or transparent, and
the side walls may be transparent, and may be darkened to restrict
access of light. Accordingly, the side walls may be formed of
plastic and/or glass, and other portions of the housing may be
formed of any suitable material including plastic, metal,
composite, glass, and/or the like.
[0140] The housing 182 may include an opening 204 formed in top
wall 200. The opening may be sized to receive a cooling device 206,
such as a thermoelectric cooler operating by the peltier effect.
The cooling device may be configured to refrigerate the interior
compartment 192 and the allergen stocks 190 housed in this
compartment. In some examples, the cooling device may be disposed
inside the housing or disposed exterior to, and/or spaced from, the
housing. If exterior to the housing, the cooling device may be
connected to the housing by one or more ducts.
[0141] Each dispenser station 186 may include a stock vial 208
holding an allergen stock 190 (or a vessel holding another fluid,
such as a diluent, excipient, drug, etc.). The stock vial may be
disposed in an upright or inverted configuration, among others, in
the dispenser station. In the present illustration, the stock vials
are inverted.
[0142] Each dispenser station 186 also may include a dispenser unit
210 attached to the housing and connected to a stock vial. The
dispenser unit may be mounted to the bottom wall of the housing.
Alternatively, or in addition, the dispenser unit may be mounted to
a side wall(s) and/or the top wall.
[0143] FIG. 9 shows a sectional view of system 180, taken generally
along line 9-9 of FIG. 8, in the absence of stock vials and their
allergen contents. Housing 182 may include a plurality of apertures
222 formed in the bottom wall 198 of the housing. Each aperture may
be configured to receive a stock vial and/or a portion (or all) of
a dispenser unit 210. In some examples, the housing may be
configured to receive the stock vial and/or dispenser unit from
underneath the housing. Alternatively, the stock vial (and/or the
dispenser unit) may be placed into (or through) the housing from
above the bottom wall, such as through the large opening 204 in the
top wall or through a door and/or opening formed in a side
wall.
[0144] Apertures 222 may be disposed generally around the pivot
axis 188 of the housing, inward of the side walls and generally
adjacent the perimeter of the bottom wall. Accordingly, the
apertures may be disposed in a circular pattern, in a polygonal
pattern (angularly disposed sets of rows, such as the hexagonal
pattern in the present illustration), in a single row or a set of
parallel rows, and/or the like.
[0145] FIG. 10 shows a partially exploded, sectional view of
selected portions of the dispensing system 180, taken generally
along line 10-10 of FIG. 8. An upper portion of the dispenser unit
210 may be received in an aperture 222 formed in the bottom wall
198 of the housing. Stock vial 208 thus may be disposed in the
interior compartment 192 of the housing 182. In particular, the
dispenser unit 222 may include a frame 223 (the dispenser housing)
having a collar or flange 224 extending from a neck portion 226 of
the frame. The flange may be received in a lower counterbore 228 of
the aperture 222 that is widened relative to an upper bore 230 of
the aperture. The flange may engage a shoulder 232 formed at the
junction of the bore and counter, to restrict upward movement of
the dispenser unit. In some examples, the lower counterbore, may be
sized and shaped so the flange 224 fits closely into the lower
counterbore, so that lateral movement of the flange (and the
dispenser unit) is restricted (see FIGS. 10 and 12).
[0146] The dispenser unit 210 may be secured to the housing 182
with a retainer 234. The retainer may be received, shown in phantom
outline at 235, in a slot 236 formed in the bottom wall 198 of the
housing and accessible from the perimeter of the bottom wall. The
slot 236 may be sized and positioned so the retainer 234 may slide
into the slot and under flange 224 of the dispenser unit. Downward
movement of the flange (and the dispenser unit) thus may be
restricted by engagement of the flange with the retainer. A lip 238
formed adjacent the slot 236 may restrict downward motion of the
retainer 234.
[0147] FIG. 11 shows a top plan view of the retainer 234, taken
generally along line 11-11 of FIG. 10. The retainer may be
generally planar with an aperture 240 that may be engaged with a
hand for insertion or removal of the retainer. The retainer also
may include a distal opening 242 configured to extend around the
neck portion 226 of the dispenser unit, below the flange 224 (see
FIGS. 10 and 12).
[0148] FIG. 12 shows a sectional view of the dispensing system,
taken generally along line 12-12 of FIG. 10, with the retainer
fully inserted into the slot 236. Stock vial 208 and dispenser unit
210 are shown in phantom outline to simplify the presentation.
[0149] FIG. 10 shows the neck portion 226 of the dispenser unit may
define an opening 252 in which the neck of the stock vial may be
received (see FIG. 13 also). A shoulder 254 formed on the body of
the stock vial may engage a rim of the neck portion 226 of the
dispenser so that the stock vial may be supported by and rest on
the dispenser unit, for example, in the inverted configuration
shown in the present illustration. As a result, the allergen stock
disposed in the stock vial may be positioned adjacent the closure
of the stock vial, which may permit a greater proportion of the
allergen stock to be dispensed from the stock vial.
[0150] FIG. 13 shows the dispenser station 186 of the dispenser
system 180 with a portion of the frame 223 of the dispenser unit
210 removed. Frame 223 may be formed from a single piece or
material, or from two or more pieces. In the present illustration,
frame 223 includes left-side and right-side components 272, 274.
The left-side component 272 is visible in FIG. 10, and the
right-side component 274 is shown in FIG. 13. The left-side and
right-side components may fit together, for example, with integral
pins 276, 278 of the right-side component 274 received in
corresponding sockets formed in the left-side component. The
left-side and right-side components, when fitted together, may
define a shell or dispenser housing that substantially encloses
other components of the dispenser unit 210.
[0151] The dispenser unit 210 may include a valve 282, a syringe
284, and a delivery needle 286. Valve 282 may be configured to
provide adjustable fluid communication between the stock vial 208,
the syringe 284, and the delivery needle 286. The valve may be a
stock cock valve, among others.
[0152] The valve may be connected to the stock vial with a flexible
conduit 288 secured to a hollow needle 290. The hollow needle 290
may extend through a septum 291 of the stock vial, to place the
fluid contents of the stock vial in fluid communication with the
valve 282. The flexible conduit 288 and/or the hollow needle 290
may be attached to a vial retainer 292, configured, for example,
with a pair of wings 294. The wings 294 may be long enough that
they cannot pass easily through the opening 252 of the neck
portion, shown at 296. Accordingly, the vial retainer may help to
hold the stock vial in the opening 252 of the neck portion and/or
to hold the flexible conduit 288 inside the frame 223 of the
dispenser unit. A vent tube 297, such as a hollow needle of small
diameter, also may be placed through the septum 291 of the stock
vial. The vent tube may function to permit passage of gas into/out
of the stock vial, but to restrict passage of liquid out of the
stock vial through the vent tube 297.
[0153] The valve 282 may be coupled to the syringe 284 by any
suitable mechanism. For example, the syringe may be connected to
the valve by a flexible conduit. Alternatively, the valve may form
a rigid connection with the valve. In the present illustration, the
valve housing 298 may form a socket 302 in which a tip 304 of the
syringe may be received. The socket 302 and/or the tip 304 may be
tapered to facilitate forming a seal between the valve housing and
the syringe tip, and/or to permit the syringe to be mated with the
housing removably. Alternatively, the syringe may be connected to
the housing by, for example, a threaded and/or a Luer-Lok
coupling.
[0154] The valve may be coupled to the delivery needle 286 by a
rigid or flexible connection. For example, in the present
illustration, a base 306 of the delivery needle 286 may be secured
to the valve housing 298, so that the disposition of the delivery
needle may be defined by the disposition of the valve housing.
Delivery needle 286 may be protected by a sheath or sleeve 308 that
reduces exposure of the exterior of the needle to contact with air,
liquid, or solid structures, and thus to potential contamination.
The sheath or sleeve may be resilient, so that the sheath can be
retracted to expose the distal end of the needle. Alternatively,
the sheath may be segmented so that it can telescope to expose the
distal end of the needle.
[0155] Syringe 284 may be disposed in a loading configuration,
shown at 309. In this loading configuration, the syringe may be
disposed vertically to provide fluid communication between the
stock vial and the syringe, indicated by arrows 310. In this
loading configuration, the delivery needle 286 may be out of fluid
communication with both the syringe and the stock vial, so that
fluid from the stock vial cannot pass directly to the delivery
needle. Furthermore, the delivery needle may be substantially
inaccessible within the frame 223 of the dispenser unit 210. In the
loading configuration, a plunger 312 of the syringe may be drawn
outward, indicated at 314, to pull a measured volume 316 of the
allergen stock 190 into the barrel 318 of the syringe.
[0156] FIG. 14 shows the dispenser station 186 of the dispenser
system 180 in a delivery configuration, indicated at 330. To
achieve this configuration, the syringe 284 may be engaged manually
and pulled and/or pushed from its vertical loading configuration
309 (see FIG. 13) to a more horizontal position (or from a
horizontal to vertical position, or between any other suitable
dispositions). The syringe may be rigidly connected to the valve
housing 298. Accordingly, turning the syringe (by orbital movement
in the present illustration), indicated at 331 in FIG. 14, may
produce coupled pivoting of the valve housing about an axis 332
defined by a stem or core 334 of the valve. Accordingly, the
syringe, extending radially from the pivot axis 332, may act as a
handle and/or lever to pivot the valve housing and thus operate the
valve. In particular, pivoting of the valve housing 298 may
reposition structures connected to the valve housing, such as a
proximal end 336 of the flexible conduit 288 and/or the delivery
needle 286 and its associated sheath 308.
[0157] Movement of the syringe 284 to the delivery position may
create fluid communication between the syringe 284 and the delivery
needle 286. Accordingly, the plunger 312 may be pushed into the
barrel, shown at 338, to cause the measured volume 316 of fluid to
flow along a path, indicated by arrows 340, from the syringe and
out of the end of the delivery needle 286, shown at 342. Prior to
release of the measured volume of fluid from the syringe, a
patient's vial 344 may be received through an opening 346 formed in
the frame 223, and into engagement with the delivery needle 286. In
particular, a septum 348 of the patient's vial may be penetrated by
the tip of the delivery needle, as the sheath 308 is retracted by
engagement with the septum (as the vial is moved upward). Delivery
of the allergen stock from the syringe to the patient's vial may be
facilitated by a vent needle 350 placed through the septum 348 of
the patient's vial. The vent needle may function as described above
for the vent tube of the stock vial.
[0158] FIGS. 15 and 16 shows fragmentary views of selected portions
of the dispenser station 186 of FIG. 13. In particular, these
figures show operation of the valve 282 of the dispenser station,
viewed from a region labeled "15" in FIG. 13 for FIG. 15 (or a
corresponding (unlabeled) region of FIG. 14 for the view of FIG.
16). Valve stem 334 of the valve may include a branched passage 352
(T-shaped in the present illustration) extending from a plurality
of positions disposed around the perimeter of the stem. As
described in more detail below in relation to FIG. 17, the passage
352 may be fixed in position, so that pairs of conduits 354, 356,
358 of the valve housing may be placed selectively in fluid
communication with the passage 352 by pivoting this housing.
[0159] FIG. 15 shows the valve housing 298 in the loading
configuration. Conduit 354 (connected to the stock vial via tubing
288) and conduit 358 (connected to the syringe 284) may be fluid
communication with the passage 352. However, conduit 356 (connected
to the delivery needle 286) may be out of fluid communication with
this passage (and thus the other conduits 354, 358). Operation of
the syringe 284 in this configuration may produce fluid flow along
path 310 between the stock vial and the syringe 284, to load the
syringe.
[0160] FIG. 16 shows the valve housing 298 in the delivery
configuration. Conduits 356 and 358 may be in fluid communication
with passageway 352, so that fluid can flow along path 340 from the
syringe to the delivery needle 286. Conduit 354 may be out of fluid
communication in this configuration, to restrict a direct flow of
fluid between the stock vial and the delivery needle.
[0161] FIG. 17 shows a fragmentary portion of the dispenser
station, as in FIG. 16, but from an opposing side of the dispenser
unit 210, with the exterior surface of right-side component 274
visible. The valve stem 334 may be substantially fixed in position
(restricted from pivoting and/or translational motion) by
engagement of the stem with the frame of the dispenser unit. In
particular, the stem may include a projection, such as a flange or
handle 382, that is received by a receiver structure or opening 384
formed in the right-side component 274 of the frame. The handle 382
may extend radially from the pivot axis 332 of the stem.
Alternatively, the frame 223 may include a projection received by
the stem to restrict pivoting of the stem. The left-side component
of the frame also may engage the valve to prevent the valve from
sliding or wobbling in the frame. For example, FIG. 12 shows an
opening 386 defined by the left-side component 272 that receives an
opposing side of the valve.
[0162] In some embodiments, handle 382 of the stem 334 may be
operable manually. Accordingly, the dispenser station may be
switchable between loading and delivery configurations by operating
the handle through manual engagement of this handle. However,
pivoting the valve housing through movement of the syringe, rather
than pivoting the stem with direct engagement of the handle 382,
may offer advantages over movement of the handle. In particular,
the syringe may provide a mechanical advantage through a longer
lever arm (to exert greater torque). Alternatively, or in addition,
use of the syringe as a lever may provide a visual indication of
individual steps of the dispensing process, based on the position
of the syringe. The rate of dispensing errors thus may be
reduced.
[0163] FIG. 18 shows the dispenser station 186 viewed generally
along line 18-18 of FIG. 13, but with the frame 223 assembled.
Frame 223 may define an elongate opening 402 extending formed
vertically in a front wall 404 of the frame. The vertical opening
402 may permit the syringe to move orbitally (compare FIGS. 13 and
14), as the valve housing 298 pivots. Accordingly, the opening 402
may extend from a bottom wall 406 to a vertical position slightly
above the valve 282. Opening 402 also may permit indicia 408 (such
as graduations and/or numbers, among others) to be visible as fluid
is loaded into the syringe. (In the present illustration, the
numbers may represent tenths of milliliters.) The indicia may be
configured to permit a measured volume of a biological fluid to be
loaded into the syringe and/or to be released from the syringe into
a receiver vial.
[0164] Vertical opening 402 may adjoin a horizontal opening 346
formed in the bottom wall 406. The horizontal or bottom opening 346
may be wider than vertical opening 402, to permit a patient's vial
to be received selectively in the bottom opening (also see FIG.
14).
[0165] FIG. 18 shows the frame also may include a guide 410
disposed adjacent the bottom opening 346. Guide 410 may be
configured to guide the patient's vial into the bottom opening, for
engagement with the delivery needle (see also FIG. 14).
Accordingly, the guide may be arcuate in shape to generally match a
cylindrical contour of the patient's vial.
Example 2
Dispensing System II
[0166] This example describes a second exemplary dispensing system
510 for transferring biological fluids between closed vessels; see
FIGS. 19-26.
[0167] FIG. 19 shows a dispensing system 510 configured as a floor
model. System 510 may be operated manually, to dispense and mix
fluids, by an operator(s) standing adjacent the system and/or
sitting in a chair adjacent the system, among others. The system
may include a housing 512 pivotably coupled to and supported by a
pedestal 514 or other support structure.
[0168] The pedestal may include a base platform 516 and a column
518 affixed to the base platform. The column may define an interior
compartment 520 in which a power supply 522, electrical connectors
(e.g., wires), a cooling mechanism (such as a fan), and/or other
electronic and/or system components may be housed. The power supply
may be configured to supply electrical power to electrically
operated components disposed in housing 512. In some embodiments,
the power supply may be configured to convert AC power to DC
power.
[0169] Housing 512 may be structured to provide or define areas for
carrying out different functions of the dispensing system. For
example, proceeding from bottom to top in the present illustration,
the housing may define (1) a dispensing area 526 for dispensing
biological fluids to supply vessels, (2) a storage area 528 for
holding and arranging the supply vessels, and (3) a thermal control
area 530 including a thermal control system 531 to control the
temperature of the supply vessels. Housing 512 also may include a
vented cover 532 that can be removed to access components of the
thermal control system.
[0170] Dispensing area 526 may be configured for mounting
dispensers below supply vessels. Accordingly, the dispensing area
may be a nonpartitioned, open space below the storage area that
permits the dispensers to be mounted at least substantially below
the housing, for example, connected to a base plate 533 of the
housing. In the present illustration, only one dispenser 534 is
shown mounted below the housing, to simplify the presentation.
However, any suitable number of dispensers may be connected to the
housing, such as four per side for a total of twenty-four in the
present exemplary system. In some embodiments, the dispensing area
may be partitioned by the housing, for example, with walls that
extend downward from the base plate to define individual housing
structures for the dispensers. Alternatively, dispenser housings
may be discrete structures that are attached removably to the
system housing or may not be used in the system.
[0171] Storage area 528 may be disposed generally between base
plate 533 and an upper plate 536. Upper plate 536 may be mounted in
a spaced relation to the base plate by column members 538 (also see
FIG. 20).
[0172] FIG. 20 shows a bottom sectional view of the storage area,
taken generally along line 20-20 of FIG. 19. The storage area may
be partitioned into a plurality of thermally isolated compartments
540 (six in the present illustration). For example, each
compartment may be defined by side walls 542 that extend around a
jacket structure 544 for receiving a set of supply vessels. The
jacket structure may be formed of a thermally conductive material,
such as metal (e.g., aluminum). A thermally insulating material may
be disposed around the jacket structure in an insulator region 546
defined between the jacket structure and side walls 542. Exemplary
thermally insulating materials that may be suitable include
thermally insulating plastics (e.g., foam insulating plastics),
nonplastics, and/or a combination thereof. Each jacket structure
thus may be thermally isolated from other jacket structures
disposed in the storage area, allowing individual thermal control
of each jacket structure (and a set of supply vials disposed in
each jacket structure). A central compartment 548 of the storage
area may hold electrical conduits, electronic components of the
system, and/or portions of the thermal control system, among
others, and/or may remain at least substantially empty.
[0173] FIG. 21 shows jacket structure 544 generally from the side
and above the jacket structure. The jacket structure may include a
plate 550 and a plurality of receiver structures 552 mounted on the
plate.
[0174] Plate 550 may be configured to provide heat conduction
between the receiver structures. The plate also or alternatively
may provide a contact (and/or attachment) site for a cooling device
554 (such as a peltier device) and a temperature sensor 556 (such
as a thermistor). Each of the cooling device and sensor may include
electrical conduits 557 that extend to another component(s) of the
thermal control system, such as a controller (see below).
[0175] Each receiver structure may be sized and shaped for
receiving an individual supply vessel. For example, the receiver
structure may provide a cylindrical cavity for receipt of a
cylindrical vessel. The receiver structure may be sized and shaped
for a close fit between the supply vessel and the receiver
structure, to promote heat conduction between the cylinder and the
supply vessel. For example, the receiver structure may be sized to
receive a supply vessel with a particular diameter and/or capacity,
such as vessel with a capacity of about 50 mL. In some embodiments,
the receiver structure also may have a length that provides contact
between the bottom of the receiver vessel (inverted in the receiver
structure) and plate 550. The receiver structure also may include a
window 558 through which the supply vessel may be viewed, for
example, so that an operator can see the fluid level and/or a label
of the supply vessel from the outside of the housing. Window 558
may be an opening in the receiver structure and/or may be formed by
different material, generally a transparent material, such as
transparent plastic or glass. Vessels may be loaded into the
receiver structures, with the vessels inverted, from below the
receiver structures, such as through openings in base plate 533
(see FIG. 19)
[0176] FIG. 22 shows a top view of system 510 with cover 532
removed (see FIG. 19) to reveal components of thermal control
system 531. The thermal control system may include a plurality of
thermal control units 580 (six are shown here) that each provide
temperature regulation for a distinct set of supply vessels. For
example, in the present illustration, each thermal control unit is
configured to control the temperature of a distinct jacket
structure 544 (and thus vessels/biological fluids disposed in the
jacket structure). The thermal control units thus may maintain
supply vessels disposed in distinct jacket structures at the same
or different temperatures.
[0177] Thermal control unit 580 may include a controller 582, a
heat sink 584, a cooling device, and a temperature sensor (see FIG.
21), among others. The controller may be, for example, a PI
(proportional, integral) controller, a PID (proportional, integral,
derivative) controller, and/or any other suitable feedback-based
controller.
[0178] The controller may be electrically coupled, shown at 586, to
the cooling device, the temperature sensor, and/or heat sink 584.
The heat sink may be configured to draw heat away from the cooling
device and jacket structure 544.
[0179] FIG. 23 shows a sectional view taken through thermal control
unit 580 and plate 550 (and a portion of receiver structures 552)
of jacket structure 544. peltier device 554 may be disposed between
jacket structure 544 and heat sink 584. The cold side of the
peltier device may engage the jacket structure and the hot side of
the peltier device may engage a thermally conductive sink block 590
of the heat sink. The sink block may be formed of a thermally
conductive material, such as metal (e.g., copper). The peltier
device and at least a lower portion of the sink block may be
surrounded laterally by a thermally insulating material, to
restrict heat flow from the sink block back to the jacket
structure, lateral to the peltier device. For example, an insulator
member 592 may be fastened to plate 550 using fasteners 594, such
that flanges 596 of the sink block engage walls of an opening 598
of the insulator member, to clamp the peltier device between the
sink block and the insulator member. In some embodiments, the
insulator member may be formed of a phenolic material. An insulator
layer 600 also may be disposed on plate 550 to restrict lateral
heat flow from the peltier device. A suitable material for layer
600 may be, for example, foamed polyvinylchloride (PVC). Further
insulation may be provided by upper plate 536 (see FIGS. 19 and 20)
formed of a thermally insulating material, such as
polyethylene.
[0180] The heat sink may be configured to dissipate heat by
conducting heat from sink block 590 to fan unit 602 via heat pipes
604. The fan unit may blow air, which has been heated by heat pipes
604, radially onto fins 606, to produce heated air, which is
released from the vented cover of the housing. In some examples,
the thermal control system may include one or more additional fans
that promote flow of heated air out of the housing, such as a fan
located centrally near the top of the housing cover. A heat sink
that may be suitable for the thermal control unit is available as a
P4 CPU Cooler from Gigabyte.
[0181] FIG. 24 shows a dispenser station 620 of system 510 (also
see FIG. 19). Dispenser station 620 may include dispenser 534
coupled to a supply vessel 622 via sealed engagement with a closure
624 of the supply vessel. Dispenser 534 may include a fluidics
mechanism 626 and a dispenser housing 628. Each of the fluidics
mechanism and the dispenser housing may be attached to the system
housing via a coupling member 630. The coupling member may be a
plate configured to fit into the system housing from underneath the
housing and may be retained in position with a retainer, generally
as shown and described for collar 224 and retainer 234 of system
180 (see FIGS. 10-12).
[0182] The fluidics mechanism may include conduit structure 631,
syringe pump 632, and check valves 634, 635. The conduit structure
may include a plurality of discrete components or assemblies
including an inlet conduit 636, a T-conduit 638, a flanged conduit
640, and an outlet conduit 642, among others. Components and/or
assemblies may be connected to one another (or to the syringe pump)
by any suitable connection, such as a standard or swabbable
Luer-Lok coupling. A swabbable Luer-Lok coupling includes a valve
that remains closed and accessible for surface treatment (such as
swabbing with a disinfectant) until coupling occurs.
[0183] Inlet conduit 636 may have any suitable structure to perform
any suitable functions. For example, the inlet conduit may be
configured to provide a sealed coupling with closure 624.
Accordingly, the inlet conduit may have a sharp tip 644 that can
pierce the closure. The inlet conduit also may include a collar or
ancillary cap 646 that engages, supports, and/or fits over the neck
of the supply vessel.
[0184] In some embodiments, the inlet conduit may include a
self-venting mechanism. The self-venting mechanism may permit air
to pass through the seal between the inlet conduit and the closure,
into the supply vessel, to relieve pressure differences between the
supply vessel and the outside air. For example, the inlet conduit
may include a widened, sloped base and projections disposed under
and elevating the supply vessel. This structure may allow air flow
to the sloped base, for upward movement along the sloped base and
into the supply vessel. However, the inlet conduit is still in
sealed engagement with the closure, to restrict the biological
fluid from leaking out of the supply vessel.
[0185] The inlet conduit (or a conduit connected to it) also may be
configured to engage support plate 630, for example, by extending
through an opening of the support plate. The inlet conduit thus may
be assembled with the support plate prior to coupling to other
components of the conduit structure (and generally prior to
installing the support plate in the system housing). For example,
the inlet conduit may be placed through the opening of the support
plate. Transverse movement of the inlet conduit relative to the
support plate then may provide increased engagement between the
inlet conduit and the support plate that holds the inlet conduit in
position relative to the support plate.
[0186] T-conduit 638 may be configured to provide unidirectional
flow of fluid along a main passage of the T-conduit. In particular,
the fluid may be restricted to flow from the inlet conduit to the
outlet conduit (and substantially not in reverse). In contrast, the
T-conduit may permit bidirectional flow through a side passage of
the T-conduit that extends to the syringe pump. FIGS. 25 and 26
illustrate schematically how check valves 634, 635 within the
T-conduit restrict reverse flow in main massage 654 during loading
and delivery movement of the syringe pump. Each of the check valves
permits fluid flow in the same direction, from the inlet conduit to
the outlet conduit, and restricts flow in the reverse direction.
Outward movement of the syringe plunger produces fluid flow,
indicated by arrow 658, that opens upper check valve 634 (upstream
of the pump and side passage 656) and closes lower check valve 635
(downstream of the pump) (see FIG. 25), thereby loading the syringe
with fluid from the supply vessel. Inward movement of the syringe
plunger produces fluid flow, indicated by arrow 660, toward the
outlet conduit, which closes upper check valve 634 and opens lower
check valve 635 (see FIG. 26), thereby delivering fluid from the
pump to the outlet conduit. Exemplary check valves that may be
suitable are duckbill valves.
[0187] FIG. 24 shows additional features of the dispenser. For
example, flanged conduit 640 may cooperate with dispenser housing
628 to form a substantially enclosed compartment 662 for the
majority of the conduit structure. In particular, the flanged
conduit may include a collar or flange 664 that extends radially
from the flanged conduit towards the dispenser housing.
[0188] The outlet conduit may include an elastomeric sheath 665
that retracts as the conduit penetrates the closure of a receiver
vessel. The elastomeric sheath may be, for example, a sleeve formed
of silicone rubber.
[0189] The dispenser housing may have any suitable structure. For
example, the dispenser housing may have a cylindrical shape with an
opening 666 for receiving the syringe. The dispenser housing may
mate with coupling member 630 to facilitate positioning the
dispenser housing on the system housing. The dispenser housing may
be formed of any suitable material, such as a transparent plastic,
to facilitate viewing the fluidics mechanism, or an opaque plastic
to reduce exposure of the fluidics mechanism to light, among
others.
Example 3
Dispenser Station with Climate Control
[0190] This example describes an exemplary dispenser station 710
including a flow system 712 that cools and pressurizes the interior
of a dispenser housing 714 of the dispenser station; see FIG.
27.
[0191] Flow system 712 may include a blower mechanism 716, a
conduit structure 718, and a filter 720, among others. The blower
mechanism may be configured to generate a stream of air 722 that is
filtered by filter 720. The filter may be any suitable mechanism
for reducing the presence of microorganisms in the air stream, such
as a HEPA filter. The conduit structure may provide a flow path for
the air stream that extends to dispenser 723 of the dispenser
station. For example, the conduit structure may include tubing 724
that carries the air stream from the blower mechanism to the
dispenser. The air stream may enter a vessel storage compartment
726 of the dispenser station. Alternatively, or in addition, the
air stream may travel through a thermally conductive conduit 728
having a temperature controlled by a thermal control system. For
example, the thermally conductive conduit may be created by a bore
formed in a jacket structure 730 in which the supply vessel is
received (see Example 2). The air stream may be cooled (or heated)
as it travels along the thermally conductive conduit, according to
the temperature of the jacket structure. The air stream thus may
enter a compartment 732 inside the dispenser housing to cool
dispenser fluidics 734. Alternatively, or in addition, the air
stream may create a net positive pressure (with filtered air)
inside the dispenser housing, to reduce entry of unfiltered air
into the dispenser housing.
[0192] The flow system may extend to any suitable number of the
dispenser stations. For example, in some embodiments, the flow
system may include a manifold with conduits that extend to each of
the dispenser stations, so that a filtered air stream travels to
each dispenser station.
Example 4
Dispenser Station with Decontamination Mechanism
[0193] This example describes an exemplary dispenser station 750
including a decontamination mechanism 752; see FIG. 28.
[0194] The decontamination mechanism, also termed a sterilizer, may
be configured to reduce the chance of contamination of dispensed
biological fluids by killing, inactivating, and/or removing
pathogens and/or other contaminants before, during, and/or after a
dispensing operation. Accordingly, the decontamination mechanism
may provide treatment with a chemical, electromagnetic radiation, a
filter, an absorber, and/or heat, among others. Operation of a
decontamination mechanism may provide any suitable calculated,
statistical, and/or actual decrease in the number of viable and/or
active (e.g., living, growing, dividing, infectious, and/or
toxicogenic) pathogens present, within a treated field, such as a
decrease to less than about a thousandth, a ten-thousandth, a
one-hundred-thousandth, or a millionth of the original level (e.g.,
at least about a "three-log kill," a "four-log kill," a "five-log
kill," or a "six-log kill"), among others. The decontamination
process may be configured to take any suitable amount of time, for
example, less than about a minute, less than about ten seconds,
less than about one second, or less than about one-tenth of a
second, among others. Exemplary pathogens may include bacteria,
mold/fungi, viruses, virions, prions, and/or the like, among
others.
[0195] In exemplary embodiments, the decontamination mechanism
irradiates a region of the dispenser station with electromagnetic
radiation, such as ultraviolet light. Accordingly, the
decontamination mechanism may include one or more ultraviolet light
sources 754. In addition, the decontamination mechanism optionally
may include one or more optical elements, including reflective
and/or refractive elements, to direct and/or intensify light, to
increase the efficacy of decontamination. Each ultraviolet light
source may provide a continuous or pulsed beam of light. The
ultraviolet light source may produce light of a suitable
wavelength(s) and intensity to kill and/or inactivate
microorganisms. Killing and/or inactivation may involve any
suitable mechanism(s), such as death, DNA dimer formation,
denaturation, cleavage, and/or the like. In some examples, the
light source may be a flash lamp or pulsed laser that delivers one
or more flashes or pulses of ultraviolet light to achieve
sterilization. Flash or pulsed sources may generate more light in
less time, while consuming less power and producing less heat, than
continuous sources. The pulses produced by a flash or pulsed source
may be less than about 1 millisecond in duration, less than about 1
microsecond in duration, less than about 100 nanoseconds in
duration, less than about 10 nanoseconds in duration, or less than
about 1 nanosecond in duration, among others. The decontamination
cycle, in turn, may involve illumination for a set period (for
continuous or pulsed sources) or a set number of pulses (for pulsed
sources). The light source may produce effective amounts of
germicidal, ultraviolet C (UV-C) light, particularly light with
wavelengths between about 100 nm and about 280 or 290 nm, more
particularly between about 230 nm and about 260 nm, and yet more
particularly about 245 nm, among others.
[0196] The decontamination mechanism may be configured to
decontaminate (or sterilize) any suitable region(s) and/or
surface(s) of the dispenser. For example, the decontamination
mechanism may be configured to decontaminate an outlet conduit 756
(such as without a sheath and/or with its sheath retracted) and/or
a receiver vessel 758, particularly a closure 760 of the receiver
vessel. The decontamination mechanism thus may be operated at any
suitable time, such as continuously, periodically, and/or a short
time before delivery of a biological fluid to a receiver vessel,
among others. Components of the dispenser, including supply or
stock vessels, receiver or patient vessels, intervening fluid
pathways, and so on, may be selected to facilitate decontamination
by the selected decontamination mechanism(s). For example, vessels
and/or intervening conduit may be selected to transmit ultraviolet
light, for use with decontamination mechanisms based on ultraviolet
light. Moreover, these components may be structured to facilitate
operation of the decontamination mechanism, for example, forming a
layer of fluid to increase the area available for illumination
while decreasing the depth required to reach all portions of the
fluid.
[0197] The decontamination mechanism may be actuated by any
suitable mechanism, including mechanically, optically, acoustically
(voice control), and/or automatically, among others. Mechanical
actuation may be performed, for example, by a switch operated
directly by a person (such as by hand or by foot (e.g., pressing a
foot pedal) or indirectly by manual placement of the receiver
vessel into the dispenser station. Optical actuation may be via an
optical sensor that optically senses the presence of the receiver
vessel. Acoustical actuation may be via a voice operated mechanism
that is controlled electronically. Automatic actuation may be via a
controller that actuates the decontamination mechanism at an
appropriate time(s) during automated dispensing.
[0198] It may be desirable to minimize human exposure to the
decontamination mechanism. Accordingly, the decontamination
mechanism may be shielded by any suitable mechanism. In some
examples, dispenser housing 762 may include a support structure 764
that supports the receiver vessel during operation of the
decontamination mechanism (e.g., to minimize exposure to the
operator's hands). In some embodiments, the support structure may
function as an elevator that moves the receiver vial upward, such
as into the housing and/or into engagement with the outlet conduit,
before, during, and/or after actuation of the decontamination
mechanism. Alternatively, or in addition, the housing may include a
shield structure 766 that allows the receiver vessel to enter the
dispenser housing but blocks exit of the decontamination agent
(such as by blocking transmission of UV light).
[0199] A dispensing system may have any suitable number of
decontamination mechanisms. For example, the system may have a
decontamination mechanism for each dispenser station.
Alternatively, the system may include fewer decontamination
mechanisms than dispenser stations, such as a single or a few
decontamination stations for use to decontaminate the tops of
receiver vessels before engagement with dispensers.
Example 5
Dispenser Station with Manually Operated Pinch Valves
[0200] This example describes an exemplary dispenser station 780
including manually operated pinch valves 782, 784; see FIG. 29.
[0201] The pinch valves may be selectively actuated by pivotal
movement of syringe pump 786. Selective actuation may provide
unidirectional flow of fluid along primary conduit 788, from a
supply vessel 790 to an outlet conduit 792. Pinch valves 782, 784
may be formed by engagement between a pivotable cam 794 (having a
pivot axis 796) and respective valve members 798, 800. Cam 794 may
be affixed to a syringe receiver 802 into which the syringe pump
can be mounted. Accordingly, the cam may be pivotable via pivotal
movement of the syringe pump, syringe receiver, and/or associated
structures. Cam 794 may be pivotable such that pivotal motion of
the cam against lower valve member 800 pinches the conduit to block
the delivery pathway, as shown here, thereby allowing fluid to be
loaded selectively into syringe 786 from supply vessel 790. Cam
also may be pivotable such that pivotal motion of the cam against
upper valve member 798 (counterclockwise in the present view)
blocks the loading pathway, thereby allowing fluid to be delivered
selectively through the outlet conduit.
[0202] The syringe pump may include a piston or plunger 804
operated by direct hand engagement or indirectly via a mechanical
assist 806. The mechanical assist may be, for example, a
rack-and-pinion mechanism 808. A rack structure 810 of mechanism
808 may be connected to the plunger handle, shown at 812, such that
translational movement of the rack structure produces corresponding
movement of the plunger (and vice versa). A pinion gear 814 of
mechanism 808 may be connected to a handle 816 that can be engaged
by hand, such that the syringe pump is operated by a hand crank 818
to move the plunger in and out. (The handle and hand crank may be
omitted, so that the plunger is moved more directly by an
operator.) A pawl 820 may provide a ratchet mechanism that
restricts reverse movement of the hand crank, until the
rack-and-pinion mechanism is pivoted away from the pawl (after
loading the pump). The mechanical assist may be configured such
that the plunger cannot be moved as rapidly as by direct engagement
of the plunger by hand, which may, for example, reduce the
formation of air bubbles in fluid lines.
[0203] Any suitable portion (or all) of dispenser station 780 may
be disposable. In some examples, the syringe and its associate
conduit structure may be disposable, and the remaining components
(e.g., the rack-and-pinion mechanism, the ratchet mechanism, the
syringe receiver, etc.) may be coupled to a dispenser housing that
is reusable. Accordingly, the syringe and conduit structure may be
supplied as a sterilized module or cassette that is installed in
the dispenser station.
[0204] Dispenser station 780 also may use operation of the
mechanical assist, and particularly operation of the
rack-and-pinion mechanism, to facilitate measurement of pump
operation. For example, the dispenser station may include a pump
sensor 822 that measures changes in the position of the
rack-and-pinion mechanism corresponding to movement of the pump
plunger. Accordingly, pump sensor 822 may be, for example, a
position sensor, such as a potentiometer, an encoder, and/or the
like. The pump sensor may be in communication with a controller 824
to forms a feedback mechanism 826 for measuring and documenting
operation of the dispenser station. In particular, the feedback
mechanism may record the volume dispensed from the dispenser into a
particular receiver vessel. In some embodiments, the controller may
include data about the particular fluids (and thus dispenser
stations) and volumes of these fluids that should be dispensed into
a receiver vessel to form a predefined mixture of biological
fluids. Accordingly, the controller may be configured to notify the
operator of an error during dispensing, if the error in volume
dispensed is too great and/or if the wrong dispenser station was
operated to dispense a fluid into the receiver vessel. Each
dispenser station of a dispensing system thus may include a pump
sensor in communication with a system controller.
Example 6
Dispenser Station with Automated Operation
[0205] This example describes an exemplary dispenser station 850
operated automatically; see FIG. 30.
[0206] Dispenser station 850 may include any suitable structure and
mechanisms that drive, monitor, and/or control automated operation
of a dispenser 852. For example, dispenser station may include a
motor-driven pump assembly 854 that moves fluid, an encoder or
other pump sensor 856 that measures operation of the pump (see
Example 5), electrically actuated pinch valves 858, 860 to direct
fluid flow, a touch display 862 to input and/or output data, and/or
a controller 864 to control operation of the various dispenser
mechanisms.
[0207] Pump assembly 854 may include a rack-and-pinion mechanism
866 coupled to a syringe pump 868, generally as described above in
relation to Example 5, and a motor 869 to drive mechanism 866 (and
thus operation of the syringe pump). Motor may be any suitable type
of motor including a rotary or linear motor. In exemplary
embodiments, the motor is a stepper motor.
[0208] Encoder (and/or a potentiometer) 856 may measure position
and/or movement of the pump assembly. For example, the encoder may
be a linear encoder that measures the position of a rack structure
870, and/or a rotary encoder that measures the rotational position
of the motor or of a pinion gear 872, among others.
[0209] Pinch valves may be actuated by a switch 874 and/or
controller 864. The switch may be disposed in a first configuration
by outward movement of rack structure 870, such that valve 858 is
open(ed) and valve 860 is closed when the plunger of the syringe
pump begins loading fluid. The switch further may be disposed in a
second configuration by inward movement of the rack structure, such
that valve 858 is closed and valve 860 is open(ed). Alternatively,
operation of the valves may be controlled via data from the
controller to coordinate operation of the valves with operation of
the motor.
[0210] Display 862 may be configured to input and/or output any
suitable data. For example, the display may present (continuously,
periodically, or upon demand) data about a biological fluid
dispensed by a dispenser station (e.g., "ragweed" to identify the
extract disposed in the supply vessel), shown at 876, and/or data
about a volume selected to be dispensed, shown at 878. The display
also may include touch-sensitive switches through which a user may
select a volume to be dispensed by touching the display. For
example, the user may slide a digit 880 along a volume scale or may
touch buttons presented by the display, among others.
Example 7
System with Multi-Tiered Dispenser Stations
[0211] This example describes an exemplary dispensing system 910
including a multi-tiered arrangement of dispenser stations 912; see
FIG. 31.
[0212] System 910 may be configured to arrange dispenser stations
both horizontally and vertically (in a three-dimensional array).
The system may include a housing 914 with a plurality of
sub-housings 916, 918, 920 arranged vertically. Each sub-housing
may be configured to receive a plurality of supply vessels, which
may be visible through windows 922. Dispensers 924 may be coupled
to the supply vessels of each sub-housing (only one dispenser per
level is shown here to simplify the presentation). The sub-housings
may be pivotable relative to one another, such that each dispenser
station can be accessed from the same side of the system by
pivoting the appropriate sub-housing. The sub-housings may have the
same diameter or may decrease in diameter towards the base of the
system. Successively smaller diameters for the sub-housings may be
suitable to provide space for dispensers below each sub-housing. In
alternative embodiments, the dispensers may be mounted adjacent
their corresponding sub-housings and/or the sub-housings may be
spaced vertically from one another, to accommodate the dispensers
without a decrease in sub-housing diameter.
[0213] System 910 may be configured to arrange biological fluids in
any suitable configuration. For example, different tiers of the
system may hold different types of biological fluids (such as
different allergen extracts), biological fluids of distinct
function (such as extracts on a first tier, drugs on a second tier,
other additives on a third tier, etc.), and/or different dilutions
of the same biological fluids (such as serial or progressive
dilutions of the same extract proceeding downward (or upward)
through the tiers).
Example 8
Dispenser Station with Stock Fluid Return Mechanism
[0214] This example describes an exemplary dispenser station 950
with a stock fluid return mechanism for returning unused stock
fluid to a supply or stock vessel; see FIG. 32ABC. This dispenser
station may be used, if at all, instead of, or in combination with,
other dispenser stations, including but not limited to dispenser
stations described elsewhere herein. The accompanying drawings show
an initial, predispense configuration (Panel A), an intermediate
configuration (Panel B), and a final, postdispense configuration
(Panel C).
[0215] Dispenser station 950 may include a supply vessel (or stock
bottle) 952, a receiver vessel (or patient bottle) 954, and a fluid
transfer mechanism 956.
[0216] The supply and receiver vessels may have any suitable size
and form, for example, as described elsewhere herein. The supply
vessel may be used to hold and supply a supply fluid, such as an
antigen stock solution, for dispensing. The receiver vessel may be
used to receive and hold a portion of the supply fluid, for
example, to form a patient solution, after dispensing. In some
embodiments, the supply vessel may be larger than the receiver
vessel; for example, the supply vessel may be about 50 mL, and the
receiver vessel may be about 5 mL, among others.
[0217] The fluid transfer mechanism similarly may have any suitable
size and form. Here, the transfer mechanism is configured to
transfer fluid from the supply vessel to the receiver vessel, and
then to return any unused fluid to the supply vessel after transfer
to the receiver vessel has been completed. The transfer mechanism,
in this embodiment, is based on pressure differentials that bias
fluid flow in the desired direction(s). These pressure
differentials may be at least about a few psi (pounds per square
inch), a few tens of psi (e.g., 30, 40, or 50 psi), a hundred psi,
or two hundred psi, among others. The usable pressure differential
may be limited by the system's ability to maintain the differential
without leaking, particularly from the upper seal around the top
vessel. The system may be designed to work without exposure to, or
input of, atmospheric air, reducing the likelihood of
contamination.
[0218] FIG. 32A shows dispenser station 950 in an initial,
predispense configuration. Supply vessel 952 contains a fluid
(e.g., an allergen stock solution) to be dispensed. Receiver vessel
954 includes a volume capable of receiving the dispensed fluid, for
example, into a buffer solution intended to dilute the dispensed
fluid and/or mix it with other dispensed fluids from other
dispenser stations.
[0219] The supply and receiver vessels are attached to transfer
system 956; however, there is no direct communication between the
two bottles. The supply vessel typically will be in place, and
cooled, from dispense operation to dispense operation. The receiver
vessel, in contrast, typically will be inserted into the system for
one dispense operation (although it may previously or subsequently
be used at other dispensing stations). The receiver vessel (at
least) may be held in place and/or inhibited from moving at least
in part by an overfitting sleeve structure 957. The supply and/or
receiver vessels further may be guided onto the respective needles
and/or held in place by any suitable mechanism(s), such as threaded
and/or Luer-Lok mechanisms.
[0220] The transfer system may include (1) a supply needle 958, in
fluid communication with the supply vessel, (2) a receiver needle
960, in fluid communication (although not necessary liquid contact)
with the receiver vessel, (3) an intervening holding reservoir 962,
shown here in a low-volume configuration, capable of receiving
fluid from the supply vessel, and holding the fluid for dispensing
into the receiver vessel, (4) a supply conduit 964 and a receiver
conduit 966 capable of routing fluid from the supply needle to the
holding reservoir, and from the holding reservoir to the receiver
needle, respectively, and/or (5) a pump 968 such as a syringe pump
selectively capable of interaction with fluid in the holding
reservoir. The holding reservoir may be defined and bounded by a
supply piston 970 and a receiver piston 972, positioned within a
transfer housing 974.
[0221] The dispenser station may be prepared for transfer in two
steps. First, the receiver vessel and supply vessel may be moved
apart, typically by moving the receiver vessel while keeping the
supply vessel fixed. For example, the receiver vessel may be moved
down, or it may simultaneously be moved down and rotated, as shown
at M1 in the drawing. This relative movement of supply and receiver
vessels increases the volume of the intervening holding reservoir,
for example, to about a few mL, to about one to three mL, or to
about two mL, among others, while drawing fluid out of the supply
vessel into the holding reservoir. Second, following the first
step, the pump may be actuated to remove air from the receiver
vessel, creating a partial vacuum that later may be used to move
fluid from the holding reservoir to the receiver vessel. Here,
where the pump is a syringe pump, the pump may be actuated by
pulling out a plunger 976, as shown at M2 in the drawing, to
withdraw air into the syringe volume. The volume of air withdrawn
may be at least about the volume of fluid to be dispensed into the
receiver vessel, or at least about a few times the volume of fluid
to be dispensed, among others. For example, in some embodiments,
the volume of air withdrawn may be about one or two mL, among
others, and the volume of fluid to be dispensed may be about 0.25
or 0.5 mL, among others.
[0222] FIG. 32B shows dispenser station 950 in an intermediate
configuration. Here, receiver vessel 954 has been moved down,
holding reservoir 962 has been expanded to a high-volume
configuration in which it has received and holds fluid from supply
vessel 952, and plunger 976 has been pulled out to pull air into
syringe pump 968. In the pictured embodiment, receiver conduit 966
has been positioned, via translational and/or rotational movement
of receiver vessel 954, to form an air path 978 between the syringe
pump and receiver vessel.
[0223] The dispenser station may effectuate transfer in two steps.
First, the receiver vessel and supply vessel may again be moved
relative to one another, to break the air path between the syringe
pump and receiver vessel, and to create an air path between the
syringe pump and the holding reservoir. Typically, this is
accomplished by moving the receiver vessel slightly down (and/or
around), as shown at M3 in the drawing, while keeping the supply
vessel fixed. Second, following the first step, the pump is
actuated to pump air into the holding reservoir. This air will move
up (under the influence of the buoyant force), and push fluid down
into the receiver vessel. Here, where the pump is a syringe pump,
the pump may be actuated by pushing in the plunger. The amount of
air pushed back into the reservoir in this configuration (e.g.,
about 0.25 or 0.5 mL) may be less than or about equal to the amount
of air withdrawn in the previous configuration (e.g., about 1 or 2
mL).
[0224] FIG. 32C shows dispenser station 950 in a final,
postdispense configuration. Here, plunger 976 has been pushed
partially or fully in, air 980 concomitantly has been injected into
holding reservoir 962, and fluid concomitantly (or shortly
thereafter) has been dispensed into receiver vessel 954.
[0225] The preceding configurations and steps may be repeated, for
example, to dispense into different receiving vessels. In some
cases, it may be possible to perform multiple dispense operations
by shuttling between the configurations shown in FIGS. 32B and 32C,
without returning to the configuration shown in FIG. 32A, until the
fluid in the holding reservoir is depleted.
[0226] The dispenser station may be returned to its initial
configuration following use, with or without an attached receiver
vessel. Significantly, moving the receiver vessel and supply vessel
toward one another will reduce the volume of the holding reservoir
from a high-volume to low-volume configuration, and push any
remaining undispensed fluid back into the supply vessel, without
ever having exposed the fluid to the contents of the receiver
vessel.
Example 9
Dispenser Station with Automated Dispense Verification and/or
Inventory Control
[0227] This example describes an exemplary dispenser station with
automated dispense verification and/or inventory control. This
station, and/or components thereof, may be used, if at all, instead
of, or in combination with, other dispenser stations, including but
not limited to dispenser stations described elsewhere herein. In
these embodiments, the station includes a mechanism for verifying
the presence and, in some cases, accuracy of fluid dispensing.
Specifically, the station includes a sensor that monitors fluid
dispensing from the supply vessel into the receiver vessel, either
by sensing the fluid as it is dispensed, and/or by sensing the
decreased fluid in the supply vessel and/or increased fluid in the
receiver vessel after it has been dispensed. The mechanism may be
used to verify the accuracy of the dispense, for example, as a
quality control mechanism, and/or the quantity of fluid in the
supply vessel, for example, as an inventory control mechanism. The
results may be used alone and/or in combination with other results
(e.g., from other sensors). In an exemplary embodiment, an inertial
sensor is attached to a vessel, such as a supply vessel and/or
receiver vessel. Suitable inertial sensors include silicon or
piezoelectric devices, which are very sensitive. Before, during,
and/or after each dispense cycle, a force and/or jerk may be
delivered to the vessel, for example, by "tapping" the vessel
sharply with an actuator, such as a voice coil actuator. The
response from the inertial sensor may be recorded, for example,
before and after dispensing. The difference in the mass of the
vessel, due to the removal or addition of fluid, can be related to
the dispensed fluid volume using well-known relationships. For
example, the total mass of dispensed fluid will be equal to the
density of the dispensed fluid times the volume of dispensed fluid.
Thus, inverting this relationship, the volume of dispensed fluid
will be equal to the total mass of dispensed fluid divided by the
density of the dispensed fluid. In most cases, the density of fluid
may be adequately approximated using the density of water or
physiological buffer.
Example 10
Selected Embodiments
[0228] This example describes selected embodiments of the present
teachings, presented as a series of indexed paragraphs.
[0229] 1. A system for dispensing biological fluids, comprising:
(A) a housing configured to hold a plurality of supply vessels
containing biological fluids; and (B) a plurality of dispensers,
each dispenser being configured to couple a supply vessel to a
receiver vessel by engagement with a closure of the supply vessel
and with a closure of the receiver vessel and being operable to
transfer a measured volume of fluid from the supply vessel to the
receiver vessel without disengagement from the supply vessel.
[0230] 2. The system of paragraph 1, wherein the housing defines a
plurality of apertures, and wherein the housing is configured to
receive the supply vessels through the apertures.
[0231] 3. The system of paragraph 1, the housing defining an
interior compartment, further comprising a cooling device operable
to cool the interior compartment.
[0232] 4. The system of paragraph 3, wherein the cooling device
includes a peltier device.
[0233] 5. The system of paragraph 1, further comprising a base,
wherein the housing is connected pivotably to the base.
[0234] 6. The system of paragraph 5, wherein the housing has a
plurality of discrete sides, and wherein the dispensers are
configured to be arranged generally along each side.
[0235] 7. The system of paragraph 1, wherein the housing includes a
bottom wall defining a plurality of apertures, and wherein the
supply vessels are configured to be received through the apertures
such that the dispensers are disposed at least substantially below
the apertures adjacent closures of the supply vessels.
[0236] 8. The system of paragraph 1, wherein each dispenser
includes a pump and at least one valve, and wherein the at least
one valve is adjustable to provide fluid communication selectively
between the pump and the supply vessel or selectively between the
pump and the receiver vessel, so that adjustment of the at least
one valve permits the pump to load fluid selectively from the
supply vessel and then deliver the fluid selectively to the
receiver vessel.
[0237] 9. The system of paragraph 8, wherein the at least one valve
is adjustable via movement of at least a portion of the pump.
[0238] 10. The system of paragraph 1, wherein each dispenser
includes a pair of conduits configured to penetrate the closure of
the supply vessel and the closure of the receiver vessel, such that
each conduit is disposed in sealed engagement with its respective
closure.
[0239] 11. The system of paragraph 1, wherein the dispenser
includes a check valve that restricts reverse flow from the
receiver vessel to the supply vessel.
[0240] 12. The system of paragraph 1, wherein the dispenser
includes a pinch valve.
[0241] 13. The system of paragraph 12, wherein the pinch valve is
configured to be actuated manually.
[0242] 14. The system of paragraph 13, wherein the dispenser
includes a pump, and wherein movement of the pump actuates the
pinch valve.
[0243] 15. The system of paragraph 12, wherein the pinch valve is
configured to be actuated electrically.
[0244] 16. The system of paragraph 1, wherein the dispenser
includes at least one valve and a syringe pump having a plunger,
and wherein the at least one valve is configured to be operated by
translational motion of the plunger.
[0245] 17. The system of paragraph 1, wherein the dispenser
includes a pump and a motor configured to drive operation of the
pump.
[0246] 18. The system of paragraph 1, wherein the dispenser
includes a decontamination mechanism configured to kill and/or
inactivate microorganisms.
[0247] 19. The system of paragraph 18, wherein the decontamination
mechanism includes an ultraviolet light source.
[0248] 20. The system of paragraph 1, wherein the dispenser
includes a pump and a sensor configured to detect operation of the
pump.
[0249] 21. The system of paragraph 20, wherein the pump includes a
piston, and wherein the sensor is configured to output a signal
related to a position of the piston.
[0250] 22. The system of paragraph 20, further comprising a
controller in communication with the sensor and configured such
that the controller uses data from the sensor to record information
about operation of the pump.
[0251] 23. The system of paragraph 22, wherein the information
relates to a volume of fluid dispensed by the pump.
[0252] 24. The system of paragraph 22, wherein the information
relates to which dispenser was operated to dispense fluid.
[0253] 25. The system of paragraph 20, wherein the sensor is a
potentiometer or an encoder.
[0254] 26. The system of paragraph 20, wherein the pump is coupled
to a rack-and-pinion mechanism, and wherein the sensor is
configured to sense position and/or movement of the rack and pinion
mechanism.
[0255] 27. The system of paragraph 22, wherein the controller is
configured to store data predefining a mixture of biological fluids
to be created, and wherein the controller is configured to actuate
generation of a signal if the mixture is not created correctly by a
person operating the dispensers.
[0256] 28. The system of paragraph 27, wherein the signal is
audible.
[0257] 29. The system of paragraph 27, wherein the controller is
configured to actuate generation of the signal if a volume
dispensed by the dispenser is outside a predefined range.
[0258] 30. The system of paragraph 27, wherein the controller is
configured to actuate generation of the signal if a biological
fluid not included in the mixture is dispensed.
[0259] 31. The system of paragraph 1, further comprising a
temperature control system and a controller, wherein the controller
is configured to monitor operation of the temperature control
system by recording temperatures sensed by the temperature control
system over a time period.
[0260] 32. The system of paragraph 1, wherein the housing includes
a plurality of sub-housings each configured to hold a plurality of
supply vessels, and wherein the sub-housings are movable relative
to one another.
[0261] 33. The system of paragraph 32, wherein the sub-housings are
pivotable relative to one another about the same pivot axis.
[0262] 34. The system of paragraph 1, wherein the dispenser
includes a housing, further comprising a blower mechanism
configured to provide a net positive pressure in the housing.
[0263] 35. The system of paragraph 34, wherein the blower mechanism
generates a stream of filtered air, further comprising a cooling
device that cools the air stream.
[0264] 36. The system of paragraph 1, wherein the housing is
configured to hold sets of supply vessels, further comprising a
thermal control system that individually regulates the temperature
of each set.
[0265] 37. A system for dispensing biological fluids, comprising:
(A) a housing configured to hold a plurality of supply vessels
containing biological fluids; and (B) a plurality of dispensers
configured to be connected to the supply vessels, each dispenser
including a syringe pump and at least one valve operated by the
syringe pump and configured such that the at least one valve is
adjustable via the syringe pump to permit (1) selective fluid
communication between the syringe pump and a supply vessel and (2)
selective fluid communication between the pump and a receiver
vessel, so that the syringe pump can draw fluid selectively from
the supply vessel and then deliver the fluid selectively to the
receiver vessel.
[0266] 38. The system of paragraph 37, wherein the at least one
valve is a stop cock valve.
[0267] 39. The system of paragraph 37, wherein the syringe pump is
movable between a loading position in which fluid can be drawn
selectively from the supply vessel and a delivery position in which
the fluid can be delivered selectively to the receiver vessel.
[0268] 40. The system of paragraph 39, wherein each dispenser
includes an outlet structure from which fluid can be delivered to
receiver vessels, and wherein the outlet structure moves to a more
accessible position when the pump is moved into a delivery position
for delivering the fluid to the receiver vessel.
[0269] 41. The system of paragraph 39, wherein each dispenser
includes an outlet structure including a sheathed, hollow
needle.
[0270] 42. A device for dispensing a biological fluid,
comprising:
[0271] a conduit structure configured to couple a supply vessel to
a receiver vessel by penetrating a closure of each vessel; and
[0272] a pump configured to move a measured volume of fluid through
the conduit structure from the supply vessel to the receiver
vessel.
[0273] 43. The device of paragraph 42, further comprising at least
one valve configured to restrict flow of the fluid in the conduit
structure.
[0274] 44. The device of paragraph 43, wherein the at least one
valve is adjustable to permit (1) selective fluid communication
between the syringe pump and the supply vessel and (2) selective
fluid communication between the syringe pump and the receiver
vessel, so that the syringe pump can draw fluid selectively from
the supply vessel and then deliver the fluid selectively to the
receiver vessel.
[0275] 45. The device of paragraph 42, wherein the device is
disposed in a package in a sterile condition.
[0276] 46. The device of paragraph 42, wherein the pump is a
syringe pump.
[0277] 47. The device of paragraph 42, further comprising a housing
configured to at least substantially enclose the conduit
structure.
[0278] 48. A method of dispensing a biological fluid, comprising:
(A) coupling a supply vessel holding a biological fluid to a
receiver vessel using a dispenser engaged with a closure of each
vessel; and (B) operating the dispenser to transfer a portion of
the biological fluid through the closures from the supply vessel to
the receiver vessel.
[0279] 49. The method of paragraph 48, wherein the steps of
coupling and operating are performed a plurality of times with the
same receiver vessel and distinct supply vessels, to form a mixture
in the receiver vessel.
[0280] 50. The method of paragraph 49, wherein the distinct supply
vessel hold different allergen extracts such that the steps of
coupling and operating form an allergen mixture in the receiver
vessel.
[0281] 51. The method of paragraph 48, wherein the steps of
coupling and operating are performed a plurality of times with the
same supply vessel and distinct receiver vessels to dispense
portions of the biological fluid to the distinct receiver
vessels.
[0282] 52. The method of paragraph 48, wherein the step of
operating the dispenser includes (1) a step of loading a pump with
the biological fluid and (2) a step of delivering the biological
fluid from the pump to the receiver vessel.
[0283] 53. The method of paragraph 48, further comprising a step of
injecting a person with the biological fluid from the receiver
vessel.
[0284] 54. The method of paragraph 48, wherein the step of
operating is performed with the supply vessel disposed in a cooled
compartment.
[0285] 55. A method of dispensing a biological fluid, comprising:
(A) coupling a dispenser to a supply vessel holding a biological
fluid and sealed by a closure; (B) loading a portion of the
biological fluid into the dispenser from the supply vessel through
the closure; and (C) delivering the biological fluid from the
dispenser to a receiver vessel, through a closure of the receiver
vessel, while the dispenser remains coupled to the supply
vessel.
[0286] 56. The method of paragraph 55, wherein the step of coupling
includes a step of penetrating the closure of the supply vessel
with a conduit, and wherein the step of loading includes a step of
moving the biological fluid through the conduit.
[0287] 57. The method of paragraph 55, wherein the steps of loading
and delivering include a step of operating a pump manually.
[0288] 58. The method of paragraph 57, wherein the step of
operating a pump manually includes a step of operating a syringe
pump.
[0289] 59. The method of paragraph 55, further comprising a step of
placing the receiver vessel into engagement with the dispenser,
wherein the step of placing is performed after the step of
loading.
[0290] 60. The method of paragraph 59, wherein the step of placing
includes a step of penetrating the closure of the receiver vessel
with a conduit.
[0291] 61. The method of paragraph 55, wherein the step of
delivering includes a step of delivering a measured volume of the
biological fluid to the receiver vessel.
[0292] 62. The method of paragraph 55, wherein the steps of
coupling, loading, and delivering are performed a plurality of
times so that different biological fluids are combined in the
receiver vessel to form a mixture of the different biological
fluids.
[0293] 63. The method of paragraph 62, wherein the step of
delivering is repeated a plurality of times with different allergen
extracts so that the different allergen extracts are mixed in the
receiver vessel.
[0294] 64. A method of dispensing a biological fluid, comprising:
(A) drawing a portion of a biological fluid into a pump from a
supply vessel; (B) operating at least one valve by movement of the
pump to create fluid communication between the pump and a receiver
vessel and to break fluid communication between the pump and the
supply vessel; and (C) delivering a measured volume of the
biological fluid from the pump to the receiver vessel.
[0295] 65. The method of paragraph 64, wherein the steps of
drawing, operating, and delivering are performed a plurality of
times with different biological fluids to form a mixture of the
biological fluids in the receiver vessel.
[0296] 66. The method of paragraph 64, further comprising a step of
disposing the supply vessel in a housing that pivots on a base
before the step of drawing.
[0297] 67. A method of forming an allergen mixture, comprising: (A)
coupling supply vessels to a plurality of dispensers, the supply
vessels holding different allergens in fluid; and (B) operating the
dispensers to deliver a portion of each allergen to a receiver
vessel while the dispensers remain coupled to the supply vessels,
to form an allergen mixture suitable for injection into a human
recipient.
[0298] 68. The method of paragraph 67, wherein the step of coupling
disposes the supply vessels in an array at least substantially
inside a housing in which the supply vessels are refrigerated.
[0299] 69. The method of paragraph 68, the housing being coupled
movably to a base, further comprising a step of moving the housing
relative to the base between operation of at least two of the
dispensers.
[0300] 70. The method of paragraph 69, wherein the step of moving
includes a step of pivoting the housing.
[0301] 71. The method of paragraph 67, wherein the step of
operating includes (1) a step of loading a pump with an allergen,
and (2) a step of delivering a measured volume of the allergen to
the receiver vessel.
[0302] 72. The method of paragraph 67, wherein the step of
operating includes a step of adjusting at least one valve for each
dispenser.
[0303] 73. The method of paragraph 72, wherein the step of
adjusting the valve is performed by movement of at least a portion
of a pump of the dispenser.
[0304] 74. The method of paragraph 67, wherein the step of
operating the dispensers includes a step of penetrating a closure
of the receiver vessel with a conduit of each dispenser.
[0305] 75. The method of paragraph 67, wherein the step of
operating includes a step of delivering the different allergens
sequentially to the receiver vessel.
[0306] 76. A method of forming a mixture of biological fluids,
comprising: (A) operating a plurality of pumps manually to transfer
a plurality of biological fluids from distinct supply vessels to
the same receiver vessel to create a mixture; and (B) monitoring
the step of operating automatically with a controller in
communication with sensors coupled to each of the pumps.
[0307] 77. The method of paragraph 76, further comprising a step of
inputting to the controller data corresponding to fluid types and
volumes to be included in the mixture before the step of
operating.
[0308] 78. The method of paragraph 77, wherein the step of
monitoring produces dispensing data, further comprising a step of
comparing the data corresponding to the fluid types and volume with
the dispensing data to determine whether or not the step of
operating was performed correctly.
[0309] 79. The method of paragraph 76, further comprising a step of
storing data produced by the step of monitoring.
[0310] 80. A system for dispensing a biological fluid, comprising:
(A) means for dispensing a biological fluid; (B) means for coupling
a supply vessel holding a biological fluid to a receiver vessel by
engagement with a closure of each vessel; and (C) means for
operating the means for dispensing to transfer a portion of the
biological fluid through the closures from the supply vessel to the
receiver vessel.
[0311] 81. The system of paragraph 80, further comprising means for
housing a plurality of supply vessels containing biological fluids,
wherein the means for housing is configured to be connected to the
means for coupling.
[0312] 82. A system for dispensing a biological fluid, comprising:
(A) means for dispensing a biological fluid; (B) means for coupling
the means for dispensing to a supply vessel holding a biological
fluid and sealed by a closure; (C) means for loading a portion of
the biological fluid into the means for dispensing from the supply
vessel through the closure; and (D) means for delivering the
biological fluid from the means for dispensing to a receiver vessel
through a closure of the receiver vessel while the means for
dispensing remains coupled to the supply vessel.
[0313] 83. A system for dispensing allergens, comprising: (A) a
plurality of means for dispensing biological fluids; (B) means for
coupling supply vessels to the plurality of means for dispensing,
the supply vessels holding different allergens in fluid; and (C)
means for operating the dispensers to deliver a portion of each
allergen to a receiver vessel while the dispensers remain coupled
to the supply vessels, to form an allergen mixture suitable for
injection into a human recipient.
[0314] 84. An apparatus for dispensing biological fluids,
comprising: (A) a housing; and (B) a plurality of dispensers
connected to the housing and configured to dispense measured
volumes of biological fluids, under substantially sterile
conditions, from supply vessels to receiver vessels that can be
selectively engaged with the dispensers while the supply vessels
remain connected to the dispensers.
[0315] 85. The apparatus of paragraph 84, wherein the housing
defines an interior compartment and a plurality of apertures, and
wherein the housing is configured to receive the supply vessels in
the apertures, with the supply vessels connected to the dispensers,
so that the supply vessels are disposed at least substantially in
the interior compartment.
[0316] 86. The apparatus of paragraph 85, further comprising a
cooling device operable to cool the interior compartment.
[0317] 87. The apparatus of paragraph 86, wherein the cooling
device is a peltier device.
[0318] 88. The apparatus of paragraph 84, further comprising a
base, wherein the housing is connected pivotably to the base.
[0319] 89. The apparatus of paragraph 88, wherein the housing
defines a pivot axis, and wherein the dispensers are configured to
be mounted to the housing at a plurality of positions around the
pivot axis, so that pivotal movement of the housing can select a
subset of the dispensers that are more accessible to a person
adjacent the housing.
[0320] 90. The apparatus of paragraph 84, wherein the dispensers
are configured to support the supply vessels in an inverted
configuration.
[0321] 91. The apparatus of paragraph 84, wherein the housing
includes a bottom wall defining a plurality of apertures, and
wherein the dispensers are configured to be secured to the bottom
wall with the supply vessels received in the apertures.
[0322] 92. The apparatus of paragraph 84, wherein each dispenser
includes a pump and a valve, and wherein the valve is operable
manually to provide fluid communication selectively between the
pump and a supply vessel or between the pump and the receiver
vessel, so that operation of the valve permits the pump to load a
measured volume of biological fluid from the supply vessel and then
deliver the measured volume to the receiver vessel.
[0323] 93. The apparatus of paragraph 92, wherein the supply
vessels and the receiver vessels include closures, and wherein the
dispensers are configured to transfer portions of the biological
fluids between the supply vessels and the receiver vessels through
the closures.
[0324] 94. The apparatus of paragraph 93, wherein the dispensers
include hollow needles to penetrate the closures.
[0325] 95. An apparatus for dispensing biological fluids,
comprising: (A) a housing; and (B) a plurality of dispensers
connected to the housing, each dispenser including a pump and a
valve operated by movement of the pump, the pump having a loading
position in which the valve permits fluid communication between the
pump and a supply vessel holding a biological fluid, and a delivery
position in which the valve permits fluid communication between the
pump and a receiver vessel, so that the pump can draw a volume of
the biological fluid from the supply vessel in the loading position
and then deliver the volume to the receiver vessel in the delivery
position.
[0326] 96. The apparatus of paragraph 95, wherein the pump includes
a syringe, and wherein the syringe is configured to be detachable
from the dispenser.
[0327] 97. The apparatus of paragraph 95, wherein the valve
includes an outer member and an inner member each including one or
more channels, the outer member being coupled pivotably to the
inner member to permit adjustable fluid communication between the
one or more channels of the outer and inner members, and wherein
movement of the pump between the loading position and the delivery
position pivots the outer member while the inner member remains at
least substantially stationary.
[0328] 98. The apparatus of paragraph 95, wherein the dispenser
includes a housing structure, and wherein the housing structure
includes stops that restrict movement of the pump substantially
outside a range of motion from the loading position to the delivery
position.
[0329] 99. The apparatus of paragraph 95, wherein each dispenser
includes an outlet structure from which the biological fluid is
delivered into the receiver vessel, and wherein the outlet
structure moves to a more accessible position when the pump is
moved from the loading position to the delivery position.
[0330] 100. The apparatus of paragraph 99, wherein the more
accessible position is configured to permit engagement of the
outlet structure with the receiver vessel by generally upward
movement of the receiver structure from underneath the
dispenser.
[0331] 101. The apparatus of paragraph 99, wherein the outlet
structure includes a sheathed, hollow needle.
[0332] 102. The apparatus of paragraph 95, wherein the dispensers
are configured to transfer the biological fluids to the receiver
vessel under at least substantially sterile conditions.
[0333] 103. A system for dispensing biological fluids, comprising:
(A) a housing defining an interior compartment configured to
receive supply vessels of biological fluids; (B) a cooling device
configured to maintain the temperature of the interior compartment
below ambient temperature; and (C) a plurality of dispensers
configured to transfer manually, under substantially sterile
conditions, measured volumes of the biological fluids from the
supply vessels to receiver vessels selectively engaged with the
dispensers.
[0334] 104. A method of dispensing a biological fluid, comprising:
(A) coupling a dispenser to a supply vessel holding a biological
fluid; (B) passing a portion of the biological fluid through a
closure of the supply vessel and into the dispenser so that the
dispenser is loaded; and (C) delivering a volume of the biological
fluid, after the step of passing, from the dispenser to a receiver
vessel disposed in fluid communication with the dispenser, the
volume flowing through a closure of the receiver vessel and into
the receiver vessel while the dispenser remains coupled to the
supply vessel.
[0335] 105. The method of paragraph 104, wherein the step of
coupling includes a step of penetrating the closure of the supply
vessel with a conduit, and wherein the step of passing includes a
step of moving the portion of the biological fluid through the
conduit.
[0336] 106. The method of paragraph 105, the closure being a
resilient septum, wherein the step of penetrating is performed with
a needle.
[0337] 107. The method of paragraph 104, wherein the step of
passing includes a step of operating a pump manually.
[0338] 108. The method of paragraph 107, the pump being a syringe
having a plunger, wherein the step of passing includes a step of
moving the plunger of the syringe.
[0339] 109. The method of paragraph 104, the volume being a
delivered volume, wherein the step of passing includes a step of
loading a loaded volume of the biological fluid into the dispenser,
and wherein the loaded volume corresponds substantially to the
delivered volume.
[0340] 110. The method of paragraph 104, further comprising a step
of placing the receiver vessel into engagement with the dispenser,
wherein the step of placing is performed after the step of
passing.
[0341] 111. The method of paragraph 110, wherein the step of
placing includes a step of penetrating the closure of the receiver
vessel with a delivery conduit.
[0342] 112. The method of paragraph 111, further comprising a step
of moving the delivery conduit after the step of passing and before
the step of penetrating.
[0343] 113. The method of paragraph 112, the dispenser including a
pump, wherein the step of moving is performed by moving the
pump.
[0344] 114. The method of paragraph 104, wherein the step of
delivering includes a step of delivering a measured volume of the
biological fluid to the receiver vessel.
[0345] 115. The method of paragraph 104, wherein the steps of
coupling, passing, and delivering are performed a plurality of
times so that different biological fluids are combined in the
receiver vessel to form a mixture.
[0346] 116. The method of paragraph 114, wherein the steps of
passing and delivering are performed with biological fluids
including allergens so that an allergen mixture is formed.
[0347] 117. A method of dispensing a biological fluid, comprising:
(A) drawing a portion of a biological fluid into a pump from a
supply vessel; (B) operating a valve by movement of the pump to
create fluid communication between the pump and a receiver vessel
and to break fluid communication between the pump and the supply
vessel; and (C) delivering a measured volume of the biological
fluid from the pump to the receiver vessel.
[0348] 118. The method of paragraph 117, wherein the steps of
drawing, operating, and delivering are performed a plurality of
times with different biological fluids to form a mixture of the
biological fluids in the receiver vessel.
[0349] 119. The method of paragraph 117, further comprising a step
of disposing the supply vessel in a housing that pivots on a
base.
[0350] 120. A method of forming an allergen mixture, comprising:
(A) coupling supply vessels to a plurality of dispensers, the
supply vessels holding different allergens in fluid; and (B)
operating the dispensers to deliver a portion of each allergen to a
receiver vial, under sterile conditions, while the dispensers
remain coupled to the supply vessels.
[0351] 121. The method of paragraph 120, wherein the step of
coupling disposes the supply vessels in an array at least
substantially inside a refrigerated housing.
[0352] 122. The method of paragraph 121, the housing being coupled
movably to a base, further comprising a step of moving the housing
relative to the base between operation of at least two of the
dispensers.
[0353] 123. The method of paragraph 120, wherein the step of moving
includes a step of pivoting the housing.
[0354] 124. The method of paragraph 120, wherein the step of
operating includes (1) a step of loading a pump with a portion of
an allergen, and (2) a step of delivering a measured volume of the
allergen to the receiver vessel, and wherein the measured volume
corresponds substantially to the portion.
[0355] 125. The method of paragraph 120, wherein the step of
operating includes a step of adjusting a valve for each
dispenser.
[0356] 126. The method of paragraph 125, wherein the step of
adjusting the valve is performed by movement of a pump of the
dispenser.
[0357] 127. The method of paragraph 120, wherein the step of
operating the dispensers includes a step of penetrating a closure
of the receiver vessel with conduit of each dispenser.
[0358] 128. The method of paragraph 120, wherein the step of
operating includes a step of delivering the portions sequentially
to the receiver vial.
[0359] 129. An apparatus for dispensing a biological fluid,
comprising: (A) means for coupling a dispenser to a supply vessel
holding a biological fluid; (B) means for passing a portion of the
biological fluid through a closure of the supply vessel and into
the dispenser so that the dispenser is loaded; and (C) means for
delivering a volume of the biological fluid, after the step of
passing, from the dispenser to a receiver vessel disposed in fluid
communication with the dispenser, the volume flowing through a
closure of the receiver vessel and into the receiver vessel while
the dispenser remains coupled to the supply vessel.
[0360] 130. An apparatus for dispensing allergens, comprising: (A)
means for coupling supply vessels to a plurality of dispensers, the
supply vessels holding different allergens in fluid; and (B) means
for operating the dispensers to deliver a portion of each allergen
to a receiver vial, under sterile conditions, while the dispensers
remains coupled to the supply vessels.
[0361] The disclosure set forth above may encompass one or more
distinct inventions, with independent utility. Each of these
inventions has been disclosed in its preferred form(s). These
preferred forms, including the specific embodiments thereof as
disclosed and illustrated herein, are not intended to be considered
in a limiting sense, because numerous variations are possible. The
subject matter of the inventions includes all novel and nonobvious
combinations and subcombinations of the various elements, features,
functions, and/or properties disclosed herein. The following claims
particularly point out certain combinations and subcombinations
regarded as novel and nonobvious. Inventions embodied in other
combinations and subcombinations of features, functions, elements,
and/or properties may be claimed in applications claiming priority
from this or a related application. Such claims, whether directed
to a different invention or to the same invention, and whether
broader, narrower, equal, or different in scope to the original
claims, also are regarded as included within the subject matter of
the inventions of the present disclosure.
* * * * *