Continuous whole blood glucose monitor
First Claim
1. A system for measuring an analyte in a complex matrix, comprising:
- a mid-infrared quantum cascade laser emitting at least one wavelength;
a photo-detector;
a means for exposing a sample of the complex matrix to the laser and photo detector; and
a means for enhancing measurement sensitivity.
3 Assignments
0 Petitions
Accused Products
Abstract
A portable continuous whole blood glucose monitor comprising, a mid-infrared quantum cascade laser and driver in optical communication with a transmission cell and a photo-conductive detector and pre-amplifier. The monitor further comprises a peristaltic pump connected to a single lumen catheter peripherally inserted into a patient'"'"'s vein. The single lumen catheter, in combination with the peristaltic pump, is operable to automatically withdraw a fixed and metered amount of whole blood from a patient, then a tube delivers a fixed and metered amount of the saline/surfactant supply to the whole blood. Methods of enhancing measurement sensitivity are also provided.
-
Citations
43 Claims
-
1. A system for measuring an analyte in a complex matrix, comprising:
- a mid-infrared quantum cascade laser emitting at least one wavelength;
a photo-detector;
a means for exposing a sample of the complex matrix to the laser and photo detector; and
a means for enhancing measurement sensitivity. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21)
- a mid-infrared quantum cascade laser emitting at least one wavelength;
-
23. A method for monitoring an analyte in a complex matrix, comprising:
-
the step of connecting a catheter to a peripheral vein of a patient and a fluid mixing valve; the step of connecting a tube to a non-ionic surfactant and saline supply and the mixing valve; the step of connecting the mixing valve to the peristaltic pump; the step of connecting the peristaltic pump to a transmission cell having a path length sized to resolve the physiological concentrations of the analyte within the sample; the step of integrating a processor with the peristaltic pump and mixing valve to draw fixed and metered amounts of both the matrix sample and of the non-ionic surfactant and saline; the step of positioning the transmission cell in the optical electromagnetic radiation path of a mid-infrared quantum cascade laser and a photo-detector integrated with hardware and an algorithm configured to calculate the analyte concentration, and displaying the results on a computer; the step of calibrating the laser and photo-detector to specify the laser intensity and the optimal set of wavelengths in a spectral region for the complex matrix where many wavelength terms may be required; the step of activating the fluidic system to first draw metered samples of the matrix and the saline and surfactant;
then to mix the sample with the surfactant and saline;
then to carry the mixture to the transmission cell;
then after the optical measurement, rinse the transmission cell with the surfactant and saline to prevent clogging and non-homogeneity on the surfaces of the infrared transmissive windows during pumping the mixed sample through the transmission cell;
the non-ionic surfactant helping to keep a constant film in the transmission cell, by reducing surface tension, by lysing red blood cells and other cells that can cause optical instabilities in the measurement reading, by solubilizing proteins, and by homogenizing the matrix sample; andthe step of activating the laser trigger to shoot many shots through the transmission cell while the sample matrix passes. - View Dependent Claims (22, 24)
-
-
25. A method of blood sampling, comprising:
-
the step of inserting a single lumen catheter into a patient'"'"'s peripheral vein; the step of withdrawing blood continuously or on demand by a peristaltic pump operating at a low speed to prevent any vein collapse and coating the fluidic path with heparin to prevent blood clotting.
-
-
26. A plasma extraction method, comprising:
-
the step of employing a porous membrane to harvest roughly half of the serum-plasma from the patient blood sample in a flow by operation where the filter membrane comprises the walls of a flow channel continuously extracting serum/plasma while the blood flows on its way to the waste container; the step of interrogating the plasma sample; the step of controlling the membrane geometry and the differential pressure across the membrane to harvest sufficient plasma for measurement while leaving enough to avoid plugging of the membrane; the step of back flushing applying a controlled back flush of the plasma to avoid plugging of the membrane by blood cells; and the step of regulating the flow rate of plasma sufficient to minimize lag time between blood withdrawal and glucose measurement.
-
-
27. An ultrafiltration extraction method, comprising:
- the steps selected from the group consisting of the step of using ultrafiltration fibers to obtain ultrafiltration from the subcutaneous space of a patient or, the step of obtaining ultrafiltrate samples derived directly from vascular system by using hemofiltration.
- View Dependent Claims (29, 31, 33, 35)
-
28. A modular continuous whole blood glucose monitor, comprising:
- a mid-infrared optical subsystem, including a tunable multi-wavelength mid-infrared quantum cascade laser, photo detector, electronics, and software; and
a microfluidic cartridge, including a transmission cell, a fluid selector valve, and blood access catheters. - View Dependent Claims (30, 32, 34, 36, 39)
- a mid-infrared optical subsystem, including a tunable multi-wavelength mid-infrared quantum cascade laser, photo detector, electronics, and software; and
-
37. A continuous whole blood glucose monitor, comprising:
- a sensor fluidic interface with a patient, a transmission cell, a single lumen catheter, a tube, a surfactant-saline supply, a mixer and a pump;
the sensor fluidic interface comprising;
a laser, a detector, a fiber coupled transmission probe comprising fiber bundles;
one end of the fiber bundles is connected to the detector and laser, the other end of the fiber bundles is proximal to a mirror to reflect the light from the laser back to the detector;
a transmission cell is fixed between the mirror and fiber-coupled transmission probe, a distance defining the path length of the transmission cell;one end of the catheter is inserted into a patient'"'"'s peripheral vein, the one end of the tube is connected to the surfactant-saline supply, the other ends of the tube and catheter are connected to the mixer and pump;
the pump carries fixed and metered amounts of the blood sample mixed with fixed and metered amounts of the surfactant-saline supply through the transmission cell.
- a sensor fluidic interface with a patient, a transmission cell, a single lumen catheter, a tube, a surfactant-saline supply, a mixer and a pump;
-
38. A continuous whole blood glucose monitor, comprising:
- a fiber coupled transmission fluidic inter face with a patient;
the interface comprising a mid-infrared quantum cascade laser, a detector, a first fiber coupled transmission probe and a second fiber coupled transmission probe, each transmission probe comprising first and second ends, and containing fiber bundles or wave guides extending from the first end of each transmission probe to the second end of the transmission probe respectively;
two transparent windows spaced apart forming a path length;
one window connected to the first transmission probe second end, the other window connected to the second transmission probe first end;
a transmission cell in between the two windows;
a tube manifold for mixing a blood sample, an anti-coagulant, and a surfactant;
the first end of first transmission probe is proximal to the laser, the second end of the second transmission probe is connected to the detector;
a double lumen catheter, and a anti-coagulant surfactant supply;one end of the catheter is inserted into a patient'"'"'s peripheral vein, the one end of the tube is connected to the surfactant-saline supply, the other ends of the tube and catheter are connected to the mixer and pump;
the pump carries fixed and metered amounts of the blood sample mixed with fixed and metered amounts of the surfactant-saline supply through the transmission cell, the light transmits from the laser through the first transmission probe through the flow cell, through the second transmission probe to the detector.
- a fiber coupled transmission fluidic inter face with a patient;
-
40. A bodily fluid monitor, comprising:
- a Mid-infrared quantum cascade laser and a photo detector, each having collimating lenses;
an ATR ZnSe crystal prism having a tip the size of a pinhead; and
a silver halide Mid-infrared fiber connecting the laser and detector with the ATR prism;
which ATR prism remotely interfaces with a patient'"'"'s bodily fluid for glucose determination;
the laser Mid-infrared, electromagnetic signals bounce off the tip through the fiber, reflecting back to the detector;
the measurement sensitivity is determined by the tip design. - View Dependent Claims (41, 42)
- a Mid-infrared quantum cascade laser and a photo detector, each having collimating lenses;
-
43. A continuous whole blood glucose monitor, comprising:
- a monochromatic, pulsed, multimode quantum cascade laser operating at around room temperature;
the quantum cascade laser comprising, a driver with an external trigger, the driver capable of generating a mid-infrared laser signal having a wavelength of 9.65 μ
m, a pulse frequency of 10 kHz, a pulse width of 100 ns, a peak power of 1000 mW;
a room temperature MCT detector package;
a thermo-electric controller module for maintaining the monitor around room temperature;
a fluidic system comprising a peristaltic pump, a demountable transmission based flow-cell, and a single lumen peripheral intravenous blood access catheter for transmitting a whole blood sample from a patient'"'"'s peripheral vein to the flow-cell, a tube;
signal processing hardware which converts the mid-infrared laser signals into analog signals;
a data acquisition card which converts the analog signals into digital signals; and
a glucose prediction algorithm which reads the data, calculates the glucose concentration in the whole blood sample and displays the results on a computer;the quantum cascade laser and driver being in optical communication with the fluidic system and infrared integrated detector package; the fluidic system further comprising, a fluid selector valve, a saline and surfactant supply, and a CBAS heparin coating having thickness of 0.2 μ
m and being non leaching, sterilizable, and hydrophilic;
the flow-cell including a pair of circular ZnSe windows spaced apart approximately 100 microns, forming a path length for microfluidic interface of a whole blood sample and the flow cell;
the path length being sized to allow the mid-infrared laser signal to pass through the whole blood sample at an optimal intensity;
the flow cell having a contained volume of less than 10 μ
l;the catheter comprising, a sterilized capillary tubing with an outside diameter of 360 μ
m, an inside diameter of 150 μ
m, an inside surface, a first catheter end and a second catheter end, and a 22 gauge sheath;
the catheter dimensions minimize blood consumption and the lag time between whole blood withdrawal and glucose measurements;
all the inside surfaces of the fluidic system are coated with the heparin coating to prevent platelet adhesion and thrombus formation on the inside surfaces, while not diluting the whole blood sample, while reducing risk of trauma to the vascular system of the patient, and while avoiding heparin induced disorders to the patient;the catheter is inserted into a patient, for extracting a fixed and metered sample of the whole blood, and is connected to the fluid selector valve;
the tube connects a fixed and metered amount of the surfactant and saline supply and mixing valve;
both the sample and the whole blood sample and the saline and surfactant are metered so that a dilution factor is controlled;
the peristaltic pump is connected to the fluid selector valve and the flow cell;
the fluid selector valve alternates between the saline and surfactant supply and the whole blood sample, every 5 minutes or at other user defined measurement intervals;the MCT detector package, comprising;
a response time of less than 9 nsec, a detectivity of 7E9 cmHz1/2/W, and a field of view of 38°
;
a detector chip and a preamplifier integrated together;
the MCT detector package provides shielding of the thermo-electric controller module;the signal processing hardware comprising, a gated integrator module with a gate having a gate width;
a boxcar averager; and
a unique Active Baseline Subtraction module;
the gated integrator and boxcar averager being designed to recover fast, repetitive, analog signals;
the gate width being sized and perfectly aligned with the external trigger on the quantum cascade laser driver, the mid-infrared laser beam passes through the flow cell, and is sensed by the MCT detector package, which package feeds the transmitted signal into the gated integrator, which gated integrator amplifies and integrates the mid-infrared laser signal while ignoring noise and interference that are present when the gate is closed;
the gated integrator then feeds the amplified and integrated mid-infrared signal into the Boxcar Averager, which averager averages the amplified and integrated mid-infrared signal improving the signal-to-noise ratio by a factor of the square root of the number of shots; and
the Active Baseline Subtraction module cancels baseline drift.
- a monochromatic, pulsed, multimode quantum cascade laser operating at around room temperature;
Specification