Point of care heparin determination system
First Claim
1. A system for determining heparin concentration in a sample, the system comprising:
- a cartridge including a fluid path, and sample port in fluid communication with the fluid path; and
a protamine Ion Selective Electrode (ISE) pair in fluid communication with the fluid path; and
a known amount of protamine disposed in fluid communication with the fluid path.
1 Assignment
0 Petitions
Accused Products
Abstract
Methods and devices for point of care determination of heparin concentration in blood are described. Cartridges including protamine ion sensitive electrodes (ISEs) and reference electrodes and systems for automatically determining heparin concentration in the cartridges are provided. Some systems add blood to a protamine bolus sufficient to bind all heparin, leaving excess protamine. The excess protamine concentration can be determined by measuring the initial slope of the electrode potential rate of change, and comparing the slope to known protamine concentration slope values In some cartridges, an oscillating pressure source moves the blood-protamine mixture back and forth across the protamine ISE. Some systems also use a second blood sample having the heparin removed or degraded to create a blank reference sample. Protamine ISEs can include polyurethane polymer, DNNS ionophore, and NPOE plasticizer. The polyurethane may include hard segments and soft segments, where both hard and soft segments may include cyclic and straight chain aliphatic moieties having essentially no ester or ether groups. Some hard segments may include methylene diphenyl groups. Some reference electrodes have the same polymer, plasticizer, and ionophore as the measurement electrode, but with a different concentration of ionophore.
-
Citations
69 Claims
-
1. A system for determining heparin concentration in a sample, the system comprising:
-
a cartridge including a fluid path, and sample port in fluid communication with the fluid path; and
a protamine Ion Selective Electrode (ISE) pair in fluid communication with the fluid path; and
a known amount of protamine disposed in fluid communication with the fluid path. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15)
-
-
16. A method for determining an initial heparin concentration in a sample, the method comprising:
-
adding an amount of protamine to the sample sufficient to bind all the heparin in the sample;
determining a remaining protamine concentration in the sample using a protamine ion-selective electrode pair; and
calculating the initial heparin concentration in the sample using the remaining protamine concentration. - View Dependent Claims (17, 18, 19, 20, 21, 22)
-
-
23. A method for determining protamine concentration, the method comprising exposing a protamine ion sensitive electrode to a sample containing an unknown protamine concentration;
-
exposing a reference electrode to the sample;
tracking the differential electrical potential between the protamine ion selective electrode and the reference electrode over time;
determining the protamine concentration at least in part as a function of the differential electrical potential between the protamine ion selective electrode and the reference electrode over time. - View Dependent Claims (24, 25, 26, 27, 28)
-
-
29. A polyion selective electrode pair comprising:
-
a first electrode including a first polymer, a plasticizer, and an ionophore for binding to the polyion, the ionophore present in a first, non-negligible concentration; and
a second electrode including the first polymer and the plasticizer. - View Dependent Claims (30, 31, 32, 33, 34, 35, 36, 37, 38, 39)
-
-
40. A method for measuring heparin in a first blood sample, the method comprising:
-
inactivating essentially all the heparin in the first blood sample to create a reference sample;
measuring the output of a first ion selective electrode pair exposed to the reference sample, the first electrode pair having a protamine ion selective electrode and a reference electrode;
measuring the output of a second ion selective electrode pair exposed to a second blood sample, the second electrode pair having a protamine ion selective electrode and a reference electrode; and
determining the second sample heparin amount including using the second electrode pair output adjusted by the first electrode pair output. - View Dependent Claims (41, 42, 43, 44, 45, 46, 47, 48, 49)
-
-
50. A heparin concentration determination system comprising:
-
a first sample chamber having a first protamine ISE pair and a first means for mixing;
a second sample chamber having a second protamine ISE pair and a second means for mixing;
a first sample delivery channel for delivering a first sample into the first sample chamber;
a second sample delivery channel for delivering a second sample into the second sample chamber; and
a heparin remover in communication with the first delivery channel for binding, degrading, and/or inactivation heparin entering the first sample chamber. - View Dependent Claims (51, 52)
-
-
53. A method for determining a heparin concentration in a sample, the method comprising:
-
adding the sample and a protamine amount sufficient to bind all the heparin expected in the sample to a sample chamber to mix the sample and protamine;
obtaining a differential electrical potential between a reference electrode and a protamine sensitive electrode over time, where the electrode are in contact with the mixed sample; and
determining the heparin concentration at least in part as a function of the slope of the differential electrical potential over time in a substantially linear region of electrical potential versus time. - View Dependent Claims (54, 55)
-
-
56. A protamine sensitive electrode comprising:
-
a protamine transporting ionophore and a polymer including a segmented polyurethane, the polyurethane comprising;
alternating harder and softer segments, linked by urethane groups;
wherein the softer segments comprise a polyurethane having the general repeating formula—
(R1—
U—
R2—
U)m—
,wherein R1 signifies a backbone comprising a first hydrocarbon chain having j carbon atoms and bonded to a cyclic aliphatic hydrocarbon ring bonded to a second hydrocarbon chain having k carbon atoms, wherein j and k are between about 4 and 12, wherein U signifies a urethane group, and wherein R2 signifies a hydrocarbon moiety essentially free of ether and ester groups and having a molecular weight of less than about 1000, and wherein the average value of m is 1 or greater, wherein the harder segments comprise a polyurethane having the general repeating formula —
(R3—
U—
R4—
U)n—
, wherein R3 and R4 signify hydrocarbon moieties essentially free of ether and ester groups,wherein R3 is selected from the group consisting of aliphatic straight chain hydrocarbons, aliphatic branched hydrocarbons, and aliphatic cyclic hydrocarbons, in which a hard segment may have one, two, or more different members selected from the group consisting of aliphatic straight chain hydrocarbons, aliphatic branched hydrocarbons, and aliphatic cyclic hydrocarbons, wherein R4 includes at least one aromatic group in the backbone, wherein where U signifies a urethane group, and wherein the average value of n is 1 or greater. - View Dependent Claims (57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69)
-
Specification