Implantable sensor and system for measurement and control of blood constituent levels

This invention is an implantable sensor and system capable of measuring, controlling, monitoring and reporting blood constituent levels. The implantable sensor for sensing in vivo the level of at least one blood constituent in mammalian vascular tissue having at least one source of radiation from infrared through visible light, arranged to direct the radiation at the tissue where it is affected by interaction with the tissue, and at least one detector. The invention also encompasses a device for measuring and controlling the level of a blood constituent, such as glucose or oxygen, and includes an implantable infrared source module for generating an output signal representative of the sensed infrared radiation. The system includes a processor module responsive to the output signal which performs spectral analysis of the output signal and generates a control signal. The system further includes other devices for dispensing doses of medications or controlling organ function in response to the control signal.

FIELD OF THE INVENTION 
The present invention relates to medical devices for sensing the level of a 
constituent in a body fluid such as blood, including but not limited to 
blood glucose, oxygen, antibiotics, enzymes, hormones, tumor markers, 
fatty acids, and amino acid levels. The present invention also relates to 
a system for control, monitoring and reporting blood constituent levels in 
response to sensed levels and to provide continuous monitoring and control 
of blood constituent levels to permit aggressive therapy and concomitant 
clinical benefit of such therapy. 
BACKGROUND OF THE INVENTION 
Metabolic processes in living organisms proceed according to an exact 
administration of chemical compounds that are manufactured and released 
throughout the organism. These chemical compounds control the function as 
well as the condition of vital organs, tissues and processes that sustain 
or exist within the organism. In many instances these chemical compounds 
can be found in the organisms fluids including blood as in the case of 
mammals. These chemical compounds in the blood are generically referred to 
as blood constituents. 
Blood Constituents 
Glucose 
A blood constituent such as Glucose is an important nutrient and indicator 
for human organisms. During periods of moderate to heavy exercise, the 
muscles utilize large amounts of glucose to release energy. In addition, 
large amounts of glucose are taken up by muscle cells in the few hours 
after a meal. This glucose is stored in the form of muscle glycogen, and 
can later be used by the muscles for short periods of extreme use and to 
provide spurts of energy for a few minutes at a time. Moreover, glucose is 
an essential nutrient for brain and spinal cord function. Glucose is the 
only nutrient that can normally be utilized by the brain, retina, and 
germinal epithelium of the gonads in sufficient quantity to supply those 
organs with their required energy. Brain tissue has an obligate 
requirement for a steady supply of blood glucose. When blood glucose 
levels fall below 50 mg/dl, memory loss, agitation, confusion, 
irritability, sweating, tachycardia, and hypertension commonly occur. 
Brain failure occurs when blood glucose levels fall below 30 mg/dl, and is 
associated with coma, hypoventilation, and vascular instability. Death may 
occur. Therefore, it is important to maintain the blood glucose 
concentration at a high enough level to provide this necessary nutrition. 
At the same time, however, it is also important that the blood glucose 
concentration not rise too high. Glucose exerts a large osmotic pressure 
in the extracellular fluid. If glucose concentration rises to excessive 
levels, this can draw water out of the cells and cause considerable 
cellular dehydration. Blood sugars above 200 mg/dl often exceed renal 
threshold producing an osmotic diuresis by the kidneys, which can deplete 
the body of fluids and electrolytes. 
The steady supply of blood glucose is tightly controlled by the pancreas 
and the liver. Following a meal, gastric digestion and intestinal 
absorption provide an increasing amount of carbohydrates, free fatty 
acids, and amino acids into the portal venous blood. Sixty percent of the 
glucose absorbed after a meal is immediately stored in the liver in the 
form of glycogen. Between meals, when the glucose concentration begins to 
fall, liver glycogen is dephosphorolated, allowing large quantities of 
glucose to diffuse out of the liver cells and into the blood stream. The 
liver, a large organ, can store six percent of its mass as glycogen. In 
contrast, muscle tissue can store only two percent of its mass as 
glycogen, barely enough to be used by the muscle as its own energy 
reserve. 
Normally, blood glucose concentration is regulated by two hormones, insulin 
and glucagon, secreted by the pancreas. Insulin is released in a bimodal 
fashion from the pancreas in direct response to a rise in blood glucose 
level and, to a lesser extent, to a rise in the blood level of free fatty 
acids and amino acids. Insulin promotes transport of these nutrients into 
the cells to be utilized for energy, to be stored as glycogen or 
triglycerides, or to be synthesized into more complex compounds such as 
proteins. 
Some individuals develop diabetes mellitus, and do not secrete insulin in 
sufficient quantities to properly regulate blood glucose. Lack of insulin 
inhibits the cell membrane transport of nutrients such as glucose, fatty 
acids, and amino acids into the cells, forcing the cells to use other 
compounds for energy and cell growth. Diabetics exhibit a decreased 
utilization of those nutrients by the cells, resulting in a marked 
increase in blood glucose concentration, an increase in triglyceride 
mobilization from the adipose tissue resulting in a marked increase in 
blood fatty acid and cholesterol concentrations, and a marked loss of 
protein on a cellular level. Many of the severe end-organ complications 
which result from diabetes are due to the cellular wasting which occurs 
secondary to abnormal amino acid uptake and protein wasting. Abnormal 
fatty acid metabolism results in elevated levels of blood concentrations 
of low-density lipoprotein (LDL), cholesterol, and free fatty acids, all 
leading to accelerated atherosclerosis and obstructive vascular disease. 
Those with diabetes are also prone to ketosis, and develop dehydration, 
acidosis, and electrolyte imbalance under stress. In some forms of the 
disease, insulin injections may be required, and other long-term 
complications such as retinopathy, blindness and kidney disease commonly 
occur. 
The pancreas also secretes glucagon, a hormone which has cellular functions 
that are diametrically opposed to those of insulin. Glucagon stimulates 
the liver to release large amounts of glucose from glycogen when the blood 
glucose concentration falls below 90 mg/dl. This system of insulin 
inhibition and glycogen release prevents glucose concentrations from 
falling dangerously low. 
In short, glucose is regulated within a narrow range between 80 and 90 
mg/dl during fasting, with a rise toward 140 mg/dl following a high 
carbohydrate meal. The liver functions as a reservoir and buffer, so that 
glucose is available to the brain during meals and during periods of 
prolonged fast. 
Type I diabetics have an absolute deficiency in insulin synthesis by the 
beta cells of the pancreas, and have the most severe clinical course if 
not aggressively managed with nutrition and insulin therapy. These 
individuals are ketosis prone and may develop a severe metabolic acidosis. 
Wide swings in blood glucose commonly occur with a high incidence of 
symptomatic hypoglycemia following insulin therapy. End organ dysfunction 
is common due to accelerated atherosclerosis, cellular protein wasting, 
and small vessel disease. 
Type II diabetics release insulin from the pancreas in a blunted fashion 
following the intake of food. Blood insulin levels do not rise 
sufficiently to prevent hyperglycemia. However, in some forms of the 
disease, insulin levels may be elevated. In addition, peripheral tissues 
of type II diabetics may possess a smaller number of membrane tissue 
receptors and possibly a down regulation of those receptors. Ketoacidosis 
is uncommon. However, hyperglycemia and hyperosmolar conditions may occur, 
leading to coma and death. Insulin therapy may or may not be required to 
maintain normal glycemia levels. Other therapies include weight loss, 
diet, and oral hypoglycemic agents which stimulate the pancreas to release 
larger quantities of insulin. 
There is no doubt that long term tight glucose control is able to 
significantly reduce the incidence of end organ complications. Control of 
blood glucose concentration in diabetic individuals by Q.I.D. insulin 
injections has, of course, been done for many years. This type of 
treatment does have a number of serious drawbacks, however. One or more 
needle sticks of the finger must be performed on a daily basis to obtain 
blood for glucose assay. Many patients suffer anxiety and discomfort when 
subjected to finger pricking. After the blood sample is obtained, the 
sample must be exposed to a surface coated with chemical agents and 
enzymes that produce a color change corresponding to glucose 
concentration. The patient or medical practitioner performing the assay 
must interpret the color change accurately, and inject a dose of insulin 
based on the glucose level. Some patients use a hand held glucometer to 
measure glucose concentrations in their blood. Many individuals experience 
anxiety and discomfort when facing injections, and resist them. Some 
individuals may have no one to administer the required injections, but 
have difficulty injecting themselves. Dosage can also be problematic. 
Color change can be misinterpreted, and it is not unusual for patients to 
miss an injection, or to be off schedule. In addition, patients even have 
difficulties when using glucometers. Syringes, which these days tend to be 
disposable, contribute to the growing problem of hazardous medical waste. 
Some of these problems have been partially dealt with in the past, but none 
of the past attempts at dealing with these problems has been entirely 
satisfactory. Non-invasive optical techniques for measuring blood glucose 
have been developed, but these techniques do not solve the problems 
associated with administering insulin injections where required. 
Non-invasive optical techniques for measuring blood glucose are prone to 
error because the interface between the sensor and the tissue changes 
constantly with manipulation and contact pressure. Skin and extremity 
blood flow also varies considerably with cardiac output, body temperature 
and level of activity. These non-invasive optical techniques typically use 
a source of infrared (IR) radiation and a detector to measure absorption, 
reflection, or some other parameter to derive information about blood 
glucose levels. The effective optical distance from the IR source and the 
detector changes with subcutaneous body fat and the variability in placing 
the sensor from day to day. In addition, non-invasive IR sensors measure 
blood glucose in a non-continuous manner, and are thereby limited to 
functioning as a glucose measuring device and not as a therapeutic device 
for the treatment of diabetes. 
Implantable pumps for administering insulin as well as other chemical 
compounds are known. It has even been proposed to automatically measure 
blood glucose and administer insulin as may be required using an 
implantable sensor and insulin pump system. The latter systems are know to 
incorporate sensors to perform chemical analysis of blood samples which 
require the introduction of chemical reagents into the patient's body. 
Typically, these reagents periodically need to be replenished, which 
imposes the requirement of access below the surface of the skin through 
which fresh reagents must be injected from time to time. No matter what 
sensor is used, insulin still must be injected approximately every 6 weeks 
into the pump reservoir by placing a thin needle through the skin. 
Moreover, commercially available implantable pumps have FDA approval only 
for the infusion of chemotherapy and Baclofen for the treatment of spastic 
leg disorders. Pumps implanted for the infusion of insulin have been 
successfully tested in humans, however, there is no clinical benefit to 
implantations without a sensor for closed-loop control. 
Oxygen 
Cells require a continuous supply of oxygen and nutrients for basic 
metabolism. Oxygen must be efficiently absorbed through the lungs and 
combined with hemoglobin in the blood for proper transport to the tissues. 
Oxygen delivery depends upon the pumping action of the heart (blood flow 
per minute) and the content of oxygen bound to hemoglobin and dissolved 
within the plasma. 
Once in the tissues, oxygen is released from the hemoglobin molecule and 
diffuses through the interstitial fluid and into each cell. The workhorse 
of any mammalian cell is the mitochondria. A series of surface bound 
enzymes within the mitochondria transfer electrons generated during the 
metabolism of glucose called the Krebs' Cycle. Oxygen acts as the final 
electron acceptor generating ATP, NADH, heat, and carbon dioxide as a 
waste product. High energy phosphate compounds such as ATP and NADH are 
generated to provide energy for most cellular metabolic processes. 
Examples of processes requiring ATP for energy include: maintaining ionic 
gradients, active membrane transport, intracellular synthesis, and cell 
reproduction. Highly metabolic tissues such as brain and heart muscle 
tolerate an inadequate delivery of oxygen and other nutrients poorly. 
Conditions that produce a low blood flow state include cardiac pump 
failure, hemorrhage, dehydration, and sepsis. The tissues attempt to 
compensate for this low blood flow state by extracting a greater portion 
of the delivered nutrients. 
When oxygen delivery is insufficient to supply the aerobic needs for ATP 
production, alternative metabolic pathways will dominate causing lactic 
acid to accumulate. Anaerobic metabolism produces an insufficient supply 
of high energy compounds and cellular functions quickly deteriorate. Ionic 
gradients are lost and repair mechanisms cease to function. Persistent low 
flow states lead to ischemic damage to various end-organs including the 
kidneys, brain, and liver. Hypoxemia and metabolic acidosis proceeds organ 
failure followed by death of the mammal. 
Large multicellular organisms require a distribution system for the 
delivery of oxygen and nutrients. The heart, blood vessels, and hemoglobin 
molecules efficiently transport oxygen and other nutrients to the 
peripheral tissues such that every cell is within diffusion distance of a 
nutrient capillary. Typically, the heart provides pulsatile blood flow 
(cardiac output) exceeding 5.0 liters per minute. During periods of 
increased metabolic activity such as exercise, infection, or following 
surgery, the cardiovascular system is required to increase the cardiac 
output several fold to meet the increased oxygen requirements. Many 
disease states compromise the cardiovascular system such that an 
inadequate supply of oxygen and nutrients reach the tissues. Chronic heart 
failure due to hypertension, ischemic heart disease, valve disease, or 
alcohol is the most common cause of death in the U.S. 
Fatigue, shortness of breath, and poor exercise tolerance are common as the 
failing heart is unable to pump sufficient quantities of blood to satisfy 
the metabolic needs of the tissues. In addition, cardiac arrhythmia may 
further compromising forward blood flow. To solve some of these problems, 
physicians are can only intervene with medications and supplemental oxygen 
improving oxygenation and blood flow to the vital organs. 
Devices and Implantable Sensors for Detection of Blood Constituents 
Devices for the detection of blood glucose incorporate an implantable 
sensor using a semipermeable membrane and an enzyme coated surface and an 
oxygen electrode have been studied for the continuous measurement of blood 
glucose. This sensor has significant drift and quickly fails due to host 
reaction and contamination of the membrane and enzyme surface. Needle-type 
amperometric glucose sensors implanted within the subcutaneous tissues and 
having an enzyme coated surface and an electrical output to an external 
processor are known, but loss of sensitivity and sensor drift occur upon 
implantation. This type of sensor, which is in the form of a thin wire, 
must be inserted through a hollow needle into the subcutaneous tissue and 
must be changed every three to four days due to enzyme depletion and 
membrane contamination. In addition, glucose concentration within the 
subcutaneous tissues lags 20 minutes behind blood glucose and varies 
between 70-80% of blood values. 
Devices for the detection of blood oxygen such as a pulse oximeter are well 
known. The oximeter measures blood oxygen by measuring the amount of light 
absorbed by hemoglobin at two different frequencies. It was observed that 
oxygenated hemoglobin absorbs light differently from that of reduced 
hemoglobin at two certain frequencies. For example, at 660 nanometers, 
reduced hemoglobin is known to absorb as much as ten times the amount of 
light as oxygenated hemoglobin, whereas oxygenated hemoglobin absorbs a 
much greater amount of light at the infrared wavelength of 940 nanometers. 
In addition, the absorbed light has a pulsatile sinusoidal component 
caused by pulsing volumes of arterial blood from the heart. 
The typical pulse oximeter has two light emitting diodes (LEDs) and a 
detecting sensor arranged in a noninvasive manner to allow emitted light 
to pass through body tissue for detection by the sensor. As the light 
passes through the body tissue it is partially absorbed as described above 
and then detected to produce an estimate of blood oxygen in the human 
body. 
Pulse oximeters have been developed for continuous measurement of in-vivo 
human blood oxygen saturation by transilluminating tissue noninvasively. 
However, these devices have several disadvantages. Because the pulse 
oximeter is external to the body and noninvasive, it can only measure red 
and infrared light transmitted through blood in human tissue, typically 
the ear or finger. As a consequence, several inaccuracies are introduced 
into the measurement of oxygenated hemoglobin by the absorption and 
dispersion of light through intervening tissues such as skin, soft tissue, 
bone, venous blood and arterial blood. In addition, the sensors of a pulse 
oximeter are susceptible to interference from ambient light, low 
perfusion, and body motion. Pulse oximetry is known in the art and further 
described in Kevin K. Tremper and Steven J. Barker, "Pulse Oximetry", 
Anesthesiology, Vol 70, pp 70-108 1989 which is incorporated herein by 
reference. 
Therefore there is a need to control levels of blood constituents, such as 
glucose concentration, oxygen, fatty acid concentration, and amino acid 
concentration without requiring blood sampling, chemical test reagents or 
reagent injections, and with continuous monitoring of levels of blood 
constituents. The present invention meets that need by providing a sensor 
which is fully implantable and can be used In-vivo, can be used 
continuously and over the long term, and which is reliable and safe. 
The present invention provides the ability to achieve close, continuous 
monitoring and control of blood constituents such as, but not limited to, 
glucose and oxygen, as well as tumor markers, antibiotics, enzymes, 
hormones, fatty acids, and amino acid levels, thereby providing a clinical 
and therapeutic breakthrough. 
SUMMARY OF THE INVENTION 
The present invention is an implantable sensor and system capable of 
measuring, controlling, monitoring, and reporting blood constituent 
levels. The invention includes an implantable device for sensing In-vivo 
the level of at least one blood constituent in mammalian vascular tissue. 
The internal device includes a communication system and a calibration 
system. 
In one aspect of the invention, the implantable device comprises at least 
one source of radiation from infrared through visible light, arranged to 
direct the radiation at the tissue. The radiation is affected by 
interaction with the tissue and detected by a plurality of detectors. The 
detectors are located with respect to the tissue to receive radiation 
affected by said tissue. The detectors each have a filter transparent to a 
discrete narrow band of radiation. Each detector provides an output signal 
representative of detected radiation in said narrow band. 
In another aspect of the invention, the implantable device comprises at 
least two sources of radiation from infrared through visible light, 
arranged to direct the radiation at the tissue. The radiation is affected 
by interaction with the tissue and detected by at least one detector. The 
detectors being located with respect to the tissue to receive radiation 
affected by said tissue. Each source is adapted to emit radiation in a 
selected number of discrete bandwidths and each detector is adapted to 
detect the radiation being emitted in the discrete bandwidth. Each 
detector provides an output signal representative of detected radiation in 
said discrete bandwidth. 
In another of its aspects, the present invention includes a device for both 
measuring and controlling the level of a blood constituent in a mammal, 
and comprises an implantable infrared source and sensor module for 
directing infrared radiation through vascular tissue such as, but not 
limited to, an artery, a vein, a vascular membrane, or vascular tissue. 
The sensor module senses the infrared radiation after it has passed 
through the tissue and generates an output signal representative of the 
sensed infrared radiation. A processor module, responsive to the output 
signal from the infrared source and sensor module, performs spectral 
analysis of the output signal and derives therefrom a control signal 
representative of the level of the blood constituent. The processor module 
or another device in communication with the processor module is used to 
control, monitor, and report the level of the blood constituent. 
In one aspect of the invention, an insulin pump is used to control the 
level of glucose by dispensing doses of insulin in response to the control 
signal. In another aspect of the invention, an implanted cardiac pacemaker 
as well as an internal cardiac defibrillator (ICD) is used to control the 
level of oxygenated hemoglobin in the blood in response to the control 
signal. In yet another aspect of the invention, an implanted dispensing 
device is used to control the level and administration of medications such 
as, but not limited to, cardiac drugs, antibiotics, or chemotherapies in 
response to the control signal. In still another aspect of the invention, 
the level of tumor markers is monitored and reported to other devices in 
response to the control signal. In all aspects of the invention, the 
system is capable of monitoring and reporting all blood constituents that 
are sensed and measured. 
In another aspect of the invention, an implantable oxygenation, hemoglobin, 
and perfusion sensor is provided to obtain frequent objective data on 
patients with chronic illnesses such as heart failure and respiratory 
failure. Patients would be monitored for changes in hemoglobin oxygen 
saturation (pulse oximeter), hemoglobin concentration (infrared 
measurement), and changes in tissue perfusion (analysis of the 
photoplethsmograph waveform) for the purpose of detecting cardiovascular 
decompensation early so that the physician can manage the problem as an 
outpatient. Visits to the emergency room and admissions to the ICU would 
significantly diminish. Data from the sensors will be stored within a 
memory chip and Physicians would be notified automatically if data changed 
significantly from data established for an individual patient's 
background. 
Typically, cardiovascular patients are not alerted to significant 
cardiovascular decompensation until overt symptoms have occurred resulting 
in the need for acute care in a n ICU following admission through an 
emergency room. With this implantable sensor of the present invention, 
physicians will be able to detect early cardiovascular decompensation and 
institute corrective therapy as required. 
Data stored in a memory by the invention can provide the patient or 
clinician, either directly of remotely, with the natural history of the 
disease process. The physician will be able to administer medical therapy 
based on an objective presentation of data and conclude from the data and 
immediately acquire information on the effects of the therapy applied. The 
invention provides the major determinants of oxygen delivery to the 
tissues which are measured by the sensor. 
For example, after a patient is stabilized following a myocardial 
infarction and the onset of heart failure and pulmonary edema, a sensor 
would be implanted under local anesthesia. The sensor would immediately 
provide and collect data directly and communicate data to an 
extracorporeal device for remote monitoring of the patient for changes in 
oxygenation, perfusion, hemoglobin concentration, and cardiac arrhythmia. 
Once discharged from the hospital, the sensor would continue to monitor 
the patient and provide data extracorporeally for significant changes in 
oxygenation, perfusion, hemoglobin concentration, and cardiac arrhythmia. 
Depending on the condition of the patient, data would be stored in a 
memory or reported directly to the patient or medical personnel for 
interpretation as required. Therefore, the present invention can 
facilitate the administration of medications, appropriately according to 
objective measured data thereby improving cardiac contractility and 
improved tissue blood flow in advance of an acute event. 
In another aspect of the invention, the implantable device comprises at 
least one radiation source consisting of at least two discrete spectral 
bands lying somewhere within the infrared through visible spectrum, 
arranged to direct the radiation at the tissue. The radiation is affected 
by interation with the tissue and detected by at least one detector. The 
different spectral bands in each source are substantially collinear and 
interact with substantially identical tissue. The detectors being located 
with respect to the tissue to receive radiation from source affected by 
said tissue. 
Discrimination amongst different spectral bands is provided by each 
spectral band having a unique temporal or frequency modulation. Each 
detector provides an output signal representative of detected radiation 
from said source. A communication means is provided to relay the output 
signal from detector to processor. A processor is used to determine level 
of blood constituent in blood.

DESCRIPTION OF THE INVENTION 
Referring now to the drawings, wherein like numerals indicate like 
elements, there is shown in FIG. 1 a representation of an implantable 
blood constituent monitoring and control system 10. 
Glucose Monitoring and Control System 
FIG. 1 shows a blood glucose monitoring and control system 10 comprising a 
sensor and an insulin pump, as it might be surgically implanted in a 
patient 12. It should be understood that FIG. 1 is not intended to be 
anatomically accurate in every detail; rather, it is intended to represent 
generally how the system 10 would be implanted. Moreover, it should also 
be understood that, while for convenience the present invention is 
illustrated and described in reference to monitoring and control of blood 
glucose, the invention is not so limited, and encompasses the monitoring 
and control of other blood constituents such as, by way of example and not 
by way of limitation, fatty acid or amino acid concentration. Several 
preferred embodiments of the invention are presented below. 
As best seen in FIG. 2, system 10 comprises a sensor assembly 14 connected 
to a processor/pump module 16 via a signal cable 18. Sensor assembly 14, 
described in greater detail below, has an opening which enables it to be 
arranged to substantially surround a blood vessel 20. Processor/pump 
module 16 is illustrated as dispensing insulin via a tube 22 into a second 
blood vessel such as a vein 24, which may be the portal vein for direct 
transport to the liver. Alternatively, processor/pump module dispenses 
insulin via a non-thrombogenic multilumen catheter including a one-way 
valve, directly into the peritoneal space adjacent the hilum of the liver. 
Insulin will be rapidly absorbed into the portal venous system and 
transported to the liver. While the processor/pump module 16 is 
illustrated as implanted within a patient's body, the pump portion of 
processor/pump module 16 may also be an external device, worn or otherwise 
carried by the patient, without departing from the present invention. 
Where an external pump is used, insulin may be delivered percutaneously 
into an infusaport implanted under the patient's skin for final transport 
to the peritoneal cavity or portal vein. Alternatively, insulin may also 
be delivered by an external device with a needle placed chronically within 
the patient's subcutaneous tissues. Moreover, when an external pump is 
used, the processor portion of processor/pump module 16 requires a data 
telemetry portion in order to telemeter command signals to the external 
pump. Insulin reservoirs and pumps, telemetry devices, and infusaports are 
all known per se, and therefore need not be described here in any great 
detail. 
Processor/pump module 16 contains a conventional insulin reservoir and 
pump. In addition to an insulin reservoir and pump, processor/pump module 
16 contains an electronic microprocessor and associated electronic 
circuitry for generating signals to and processing signals from sensor 
assembly 14 and for generating control signals to the insulin pump itself. 
Processor/pump module 16 further includes a long-life battery to power the 
electronic circuitry, the sensor assembly 14 and the insulin pump. 
Blood Constituent Sensor 
Sensor assembly 14 is illustrated in greater detail in FIGS. 3 and 4. 
Sensor assembly 14 has a body portion 26 which is generally C-shaped in 
transverse cross-section. Thus, body portion 26 has a longitudinal channel 
which runs through body portion 26, and a longitudinal gap 28 which 
communicates with the longitudinal channel. Body portion 26 is preferably 
fabricated from a semi-rigid material such as titanium or epoxy, which is 
easily worked and biocompatible for long-term implantation. The shape and 
semi-rigid material of sensor assembly 14 enables it to be placed closely 
around vessel 20 and place optical sources and individual optical 
detectors in optimum position with respect to vessel 20. The distance 
between the optical sources and the optical detectors can thus be made 
small and as close to constant as possible, for optimum signal 
acquisition. 
In the embodiment of sensor 14 illustrated in FIGS. 3 and 4, the optical 
sources and optical detectors may be infrared (IR) sources and IR 
detectors, although radiation from infrared through the visible spectrum 
may be employed without departing from the invention. In the figures, 
individual IR sources and individual IR detectors are grouped together in 
three groups, or arrays, 30, 32, and 34. Each array comprises an IR source 
(30a, 32a, and 34a, respectively) and two IR detectors (30b, 30c; 32b, 
32c; and 34b, 34c, respectively). The individual IR sources 30a, 32a, and 
34a may be miniature infrared diodes located, in the illustrated 
embodiment, on one side of vessel 20. IR sources 30a, 32a, and 34a are 
driven by signals generated in the processor/pump module 16 and 
transmitted to IR sources 30a, 32a, and 34a via conductors 36a, 38a, and 
40a, respectively. Similarly, output signals from individual detectors 
30b, 30c; 32b, 32c; and 34b, 34c are transmitted to processor/pump module 
16 via conductors 36b, 36c; 38b, 38c; and 40b, 40c, respectively. 
Conductors 36, 38, and 40 collectively are dressed together to form signal 
cable 18, which couples sensor array 14 to processor/pump module 16. Cable 
18 exits body portion through an extension portion 42, which serves to 
support cable 18 and minimize the chance of breakage of conductors 36, 38, 
and 40 from flexing or being subjected to sharp bends. If desired, cable 
18 may exit extension portion 42 through a strain relief sleeve 44, to 
further protect cable 18. 
Each IR source 30a, 32a, and 34a has associated with it an optical filter 
46a, 48a, and 50a, respectively. Each filter transmits a different 
discrete narrow band of radiation. In similar fashion, each detector 30b, 
30c; 32b, 32c, and 34b, 34c has associated with it an optical filter 46b, 
46c; 48b, 48c; and 50b, 50c, respectively. In this manner, each optical 
source and the detectors associated with it in a given array 30, 32, or 34 
operates in only a discrete narrow band. 
With this embodiment, detectors 30b, 32b, and 34b are arranged 
diametrically opposite IR sources 30a, 32s, and 34a, respectively, to 
detect light transmitted from the associated source through the blood 
vessel 20. The angle between the sources and the detectors is thus 
180.degree.. (These detectors could also be used to determine reflected 
light, since light that is not transmitted may, for purposes of the 
invention, be assumed to have been reflected. By determining the amount of 
light transmitted, and subtracting it from the amount of light emitted 
from the source, the amount of light reflected can be calculated.) 
Detectors 30c, 32c, and 34c are arranged at an angle less than 180.degree. 
from the associate sources, and are located to detect IR radiation either 
reflected or scattered from vessel 20. 
It is important to note that, although this embodiment of the invention is 
described using three arrays of IR sources and associated detectors, that 
precise configuration is not crucial to the invention. The invention may 
be implemented, for example, using a single IR source and multiple 
detectors for detecting reflected, scattered, and transmitted IR 
radiation. In such an embodiment, the IR source would not have a narrow 
band filter associated with it, but would emit broadband IR. Each 
detector, however, would have a narrow band filter associated with it, so 
that it would respond only to a preselected wavelength. 
Conductors 36, collectively, 38, collectively, and 40, collectively, can be 
either electrical conductors or optical fibers. That is, the IR sources 
and the IR detectors may be located either within sensor assembly 14 
itself, in which case the conductors are electrical conductors and carry 
electrical signals between processor/pump module 16 and sensor assembly 
14, or within processor/pump module 16, in which case the conductors are 
optical fibers and carry infrared radiation between processor/pump module 
16 and sensor assembly 14. 
It will be appreciated that IR radiation generated by IR sources 30a, 32a, 
and 34a is directed through the walls of vessel 20, and thus the blood 
flowing in the vessel, to detectors 30b, 30c; 32b, 32c; and 34b, 34c 
located across from and at right angles to the IR sources. The IR 
radiation detected by the several detectors is, of course, affected by its 
interaction with vessel 20 and the blood flowing therethrough. 
Consequently, by analyzing the output signals from the several detectors, 
it is possible to derive information about the levels of glucose, fatty 
acids, and amino acids in the blood flowing through vessel 20. Preferably, 
although not necessarily, selected sensor/detector pairs are used for 
different measurement techniques. For example, pair 30a, 30b could be used 
to measure infrared transmittance, and pair 30a, 30c to measure infrared 
scattering. That is, the output signals from the several detectors can be 
processed differently to obtain different characteristics of the blood 
being measured. 
In contrast to prior electro-chemical glucose sensors, sensor array 14 does 
need require direct contact with blood, does not need to be replenished 
with test reagents, and can operate indefinitely. 
Alternative Blood Constituent Sensor 
In another embodiment, source 30a or 32a, or 32a) may consist of multiple 
LEDs or multiple laser diodes, each of a different wavelength spaced 
identically collinear or spaced very closely so that each wavelength has 
substantially the identical optical path ad interacts with substantially 
identical tissue. The detector 30b or c, 32b or c, and 34b or c detects 
light from each individual wavelength from source 30a, 32a, and 32c, 
respectively. The processor discriminates amongst the different 
wavelengths by having each wavelength pulse at a different frequency or at 
a different time. As the processor can discriminate amongst the different 
wavelengths by either different frequency or temporal information, narrow 
wavelength filters 46a, 48a, and 50a are unnecessary in this embodiment. 
Multiple sources and multiple detectors provide redundancy or 
alternatively the ability to measure different chemical species, although 
in many cases a single source and detector is adequate. The operation of 
the sensor is otherwise the same as described in the previous embodiment. 
Vascular Membrane Sensor Interface 
An alternative form of device 10' according to the present invention is 
illustrated in FIGS. 5 through 8. In alternative form 10', the device 
monitors blood flowing through a highly vascular membrane, such as a 
portion of the parietal peritoneum 52. The parietal peritoneum is an ideal 
tissue for measurement due to its high vascularity, translucency, constant 
temperature, and brisk blood flow. As best seen in FIGS. 6 and 7, a 
portion of a vascular membrane such as the parietal peritoneum 52 (shown 
in phantom in FIG. 6) is sandwiched between two halves 54 and 56 of an 
alternate form 58 of sensor assembly. Halves 54 and 56 are essentially 
mirror images of each other, and define a gap 60 between them, which 
receives the peritoneal tissue. Sensor assembly 58 is preferably molded 
from the same type of material as used to fabricate sensor assembly 14, as 
already described. The shape and semi-rigid material of sensor assembly 58 
enable it to be clamped snugly around peritoneal tissue 52 and to place 
individual IR sources 62a though 62d and individual IR detectors 64a 
through 64d, 66a through 66d, 68a through 68d, and 70, in optimum position 
with respect to tissue 52. 
One half of sensor assembly 58, such as half 56 for example, contains the 
individual IR sources 62a through 62e, while the other half, such as half 
54, for example, contains the individual detectors 64 collectively, 66 
collectively, 68 collectively, and 70. The detectors are grouped together 
in groups of three, for example, such as 64a, 66a, and 68a, and are 
located opposite a source, such as 62a. Only a single detector 70 is shown 
located opposite source 62e, although a group of detectors could also be 
located opposite source 62e. 
IR sources 62, collectively, are driven by signals generated in the 
processor/pump module 16 and transmitted to IR sources 62a through 62e via 
conductors 72a through 72e, respectively. Similarly, output signals from 
individual detectors 64a through 64e, 66a through 66e, 68a through 68e, 
and 70 are transmitted to processor/pump module 16 via conductors 74a 
through 74e, 76a through 76e, 78a through 78e, and 80, respectively. 
Conductors 72, collectively, are dressed together to form a signal cable 
82, while conductors 74 collectively, 76 collectively, 78 collectively, 
and 80 are dressed together to form a signal cable 84. Cables 82 and 84 
are merged together into a single signal cable 86 (see FIG. 6), which 
connects sensor assembly 58 to processor/pump module 16. 
As with conductors 36, 38, and 40, conductors 72, 74, 76, 78, collectively, 
and 80 can be either electrical conductors or optical fibers. That is, the 
IR sources 62, collectively, and the IR detectors 64, 66, 68, 
collectively, and 70 may be located either within sensor assembly 58 
itself, in which case the conductors are electrical conductors and carry 
electrical signals between processor/pump module 16 and sensor assembly 
58, or within processor/pump module 16, in which case the conductors are 
optical fibers and carry infrared radiation between processor/pump module 
16 and sensor assembly 58. 
IR radiation generated by IR sources 62, collectively, is directed through 
peritoneal tissue 52, and thus the blood flowing through the tissue, to 
detectors 64, 66, 68, collectively, and 70 located across from the IR 
sources. As in the previous embodiment, each source or detector may have 
associated with it a narrow band filter, so that each optical source and 
the detectors associated with it in a given array operate in only a 
discrete narrow band of IR radiation. The IR radiation detected by 
detectors 64, 66, 68, collectively, and 70 is, of course, affected by its 
interaction with tissue 52 and the blood flowing therethrough. 
Consequently, by analyzing the output signals from the detectors, it is 
possible to derive information about the blood flowing through tissue 52. 
Preferably, although not necessarily, selected sensor/detector pairs are 
used for different measurement techniques, such as, for example, infrared 
transmittance, infrared reflectance, and infrared scattering. Thus, the 
output signals from the individual detectors can be processed differently 
to obtain different characteristics of the blood being measured. 
Alternative Sensor Configuration 
A third embodiment 88 of sensor assembly is illustrated in FIGS. 9 and 10. 
In those figures, sensor assembly 88 comprises a generally rectangular 
array of source/detectors 90 disposed on opposite halves 92 and 94 of the 
sensor assembly, with each half being on opposite sides of a vascular 
membrane 52. Source/detectors 90 are preferably, although not necessarily, 
arranged opposite one another on respective halves 92 and 94, so that the 
array on one half is substantially in alignment with the array on the 
other half. 
An individual source/detector 90 is illustrated in more detail in FIG. 11. 
Source/detector 90 is generally circular, and at its center portion 
contains a source segment 96, from which infrared radiation is emitted. An 
inactive buffer ring 98 surrounds source segment 96. A second inactive 
buffer ring 100 is radially spaced from and surrounds buffer ring 98. 
Buffer rings 98 and 100 are inactive in the sense that they neither emit 
nor respond to IR radiation. The portion of source/detector 90 between 
buffer rings 98 and 100 is divided into a plurality of detector segments 
102, each of which is associated with a narrow band filter so that it 
responds to a selected band of radiation. A linearly-variable filter can 
be used, for example. In this manner, each detector segment 102 operates 
in only a discrete narrow band. A second plurality of detector segments 
104 is located radially outward of buffer ring 100, each of which is also 
associated with a narrow band filter so that it, too, responds to a 
selected band of radiation. 
It will be appreciated that a single source/detector 90 can operate to 
measure both reflected and scattered IR, or a single pair of 
source/detectors 90 can operate to measure reflected, scattered, and 
transmitted light over a plurality of discrete radiation bands. 
FIG. 12 illustrates an embodiment 106 of a sensor assembly similar to those 
shown in FIGS. 7 and 10, except that the two halves 108 and 110 are not 
spaced apart by a fixed distance, as are the halves of the detectors in 
FIGS. 7 and 10. Instead, the halves 108 and 110 are movable toward and 
away from each other, and the gap 112 may be adjusted by means of 
adjusting screws 114. Preferably, the head portion of screw 114 is made 
captive, but freely rotatable, in one half, such as half 108. The shank 
portion of the screw is received in a threaded bore 116 in the opposite 
half. Thus, by rotating screw 114, the width of the gap 112 between halves 
108 and 110 can be easily adjusted for optimum spacing of the individual 
sources and detectors relative to the vascular membrane 52. 
Oxygenation and Tissue Perfusion Monitoring 
FIG. 13b illustrates this concept can be summarized using the following 
equations: 
A. Oxygen delivery=cardiac output.times.oxygen saturation 
(%).times.hemoglobin concentration (gm/dl).times.1.39+partial pressure of 
oxygen (PaO2).times.0.0031 
B. Cardiac output=heart rate.times.stroke volume 
Cardiac output is a measurement of blood flow (liters/minute) and can be 
defined as the heart rate times the stroke volume. The stroke volume is 
the amount of blood ejected with each beat of the heart and is influenced 
by th amount of blood returning to the heart, the state of contractility 
of the heart muscle, and degree of afterload or impedance to forward blood 
flow. (72 bts/min.times.80 ml/bt=5,760 ml/min). Heart rate can be measured 
by counting the plethysmograph pulse wave as shown in FIG. 13b. 
Stroke volume can be estimated by analyzing the plethysmograph pulse wave 
illustrated in FIG. 13d including the maximum amplitude, the area under 
the curve, the rate of upstroke, and the velocity of wave propagation 
according to standard processing techniques. Current research is 
correlating pulse wave analysis with invasive monitoring such as Swan Ganz 
catheters and transesophageal echocardiography. Current pulse oximeter 
technology displays a pulse wave reflecting the volume of blood perfusing 
the tissue between the source and detector. Pulse detection algorithms 
evaluate the changes in light attenuation across a vascular tissue 
(photoplethysmography). The optical path length of the diastolic tissue 
bed and the optical path length of the systolic tissue bed is measured. 
The difference between the two is the optical path length of light being 
affected only by arterial blood. The microprocessor continually calculates 
the ratio of light absorption associated with both wavelengths of light 
emitted by the two source diodes. With diminished blood flow, conventional 
pulse oximeters increase the gain on the signal with no attempt to measure 
blood flow or pulse wave velocity. With sufficient gain on the signal and 
noise rejection algorithms, an accurate oxygen saturation measurement can 
be maintained despite a fall in tissue blood flow to less than 10% of 
baseline. Some commercially available pulse oximeters display the signal 
gain required (2.times., 4.times., 8.times., etc.) to maintain a normal 
amplitude plethysmograph waveform and an accurate hemoglobin oxygen 
saturation reading. Analysis of the raw signal that produces the pulse 
wave includes the maximum amplitude, the area under the curve, the rate of 
upstroke, and the velocity of wave propagation. This raw signal data can 
be used to estimate the stroke volume per beat of the heart (volume of 
blood ejected per beat). The velocity of wave propagation can be measured 
using two or more source/detector pairs in series such that the pulse wave 
is detected with a slight time delay at the second pair and an additional 
time delay at the third. Since the distance between the sensor pairs is 
known and fixed, a pulse wave velocity can be calculated. The total 
combined analysis of the pulse wave will be used to estimate stroke volume 
and therefore an on-line estimate of cardiac output. 
The amount of radiation absorption and scattered is significantly 
diminished by using a thin translucent vascular membrane as the optical 
interface. A higher signal to noise ratio is found compared to 
non-invasive pulse oximetry techniques. 
C. Oxygen content within the blood=hemoglobin oxygen saturation 
(%).times.hemoglobin concentration (gm/di).times.1.39+partial pressure of 
oxygen (PaO2).times.0.0031 
Hemoglobin oxygen saturation reflects the sigmoidal shaped dissociation 
curve in which hemoglobin is 98% saturated or greater when the partial 
pressure of oxygen exceeds 100 mm Hg. Saturation slowly falls such that 
hemoglobin is 95% saturated at an oxygen partial pressure of 60 mm Hg. 
Below this partial pressure, oxygen saturation falls dramatically. 
Commercially available pulse oximeter technology provides this information 
accurately and reliably. 
Infrared spectroscopy is able to accurately measure blood hemoglobin 
concentration. Since 1.39 milliliters of oxygen can bind to each gram of 
hemoglobin, the total oxygen content of the blood can therefore be 
measured using optical means. The amount of oxygen dissolved in the plasma 
is negligible (partial pressure of oxygen (PaO2).times.0.0031) and of 
little clinical significance. 
The purpose of the implantable oxygenation, hemoglobin, and perfusion 
sensor is to obtain frequent objective data on patients with chronic 
illnesses such as heart failure and respiratory failure. Patients would be 
monitored for changes in hemoglobin oxygen saturation (pulse oximeter), 
hemoglobin concentration (infrared measurement), and changes in tissue 
perfusion (analysis of the photoplethsmograph waveform) for the purpose of 
detecting cardiovascular decompensation early so that the physician can 
manage the problem as an outpatient. Visits to the emergency room and 
admissions to the ICU would significantly diminish. Data from the sensors 
will be stored within a memory chip and reviewed by the physician during 
an office visit or over the phone. In one embodiment, the physician would 
be notified automatically if data changed significantly from the 
individual patient's normal pattern. Typically, patients wait until 
significant cardiovascular decompensation has produced overt symptoms 
requiring admission through the emergency room to the ICU. With this 
implantable sensor, physicians will be able to detect early decompensation 
and institute corrective therapy as an outpatient. Data stored in the 
memory chip will provide the clinician with the natural history of the 
disease process. The physician will be able to titrate medical therapy 
based on objective numbers and conclude from the data the benefits 
incurred by this therapy. All of the major determinants of oxygen delivery 
to the tissues can be measured with this sensor. For example, a patient 
develops heart failure and pulmonary edema following a myocardial 
infarction. Once stabilized in the ICU a sensor would be implanted under 
local anesthesia and data collected on-line. Once discharged from the 
hospital, the sensor would monitor the patient for significant changes in 
oxygenation, perfusion, hemoglobin concentration, and cardiac arrhythmia. 
If no significant changes occur, data would be stored in a memory chip and 
downloaded for physician interpretation during the patient's routine 
office visit. Medications that improve cardiac contractility and improve 
tissue blood flow could be titrated to objective endpoints rather than to 
vague patient symptoms. 
Alternate clinical uses for this optical technology include integration of 
the output signal with an internal cardiac defibrillator (ICD). Patients 
are implanted the ICD following a near death experience due to a serious 
ventricular arrhythmia of the heart. Unfortunately, the electrocardiogram 
algorithms programmed into the ICD are unable to differentiate a life 
threatening arrhythmia from noise in certain cases. It is estimated that 
inappropriate defibrillation occurs 30% of the time. Using the implantable 
photoplethsmograph sensor (pulse oximeter), tissue blood flow data can be 
integrated with the algorithm for defibrillation. Both the ECG and tissue 
blood flow have to agree that a life threatening arrhythmia is present 
before defibrillation. 
Closed-loop feedback with a programmable pacemaker provides a means to 
increase/decrease the heart rate and fine tune the timing intervals of a 
pacemaker to more physiologically meet the oxygenation and perfusion needs 
of the tissues during various levels of physical activity. The sensor 
would be placed on around a central vein returning to the right heart. 
Measurement of venous oxygen saturation reflects the adequacy of cardiac 
output and oxygen delivery to the peripheral tissues. During exercise, 
blood flow increases several fold to the muscles and other tissues. When 
the heart is paced at a fixed low rate, the tissues extract a greater 
percentage of the oxygen delivered. Low venous saturation suggests the 
need to increase oxygen delivery by increasing the cardiac output and by 
increasing the oxygen carrying capacity of the blood (transfusion red 
blood cells, iron therapy). Decreasing venous oxygen saturation would 
signal the pacemaker to increase the heart rate and to optimize the timing 
intervals between atrial and ventricular contraction thus regulating the 
cardiac output of the heart. Once the oxygen debt was satisfied, the heart 
rate would slowly return to baseline values. In this way, the pacemaker 
would compensate for an increased demand for oxygen in the peripheral 
tissues. 
FIG. 13a illustrates a functional block diagram of a blood oxygen and 
perfusion monitoring and control system 200 comprising an implanted sensor 
330 (shown in FIG. 13c) and an implanted control module 300 (not shown in 
detail) which is in communication with an extracorporeal monitor 210. The 
extracorporeal monitor 210 is in communication with a direct blood 
calibration module 400 (explained in detail below) and other communication 
systems such as, but not limited to, a cellular telephone 220, an 
emergency medical warning system (not shown), or a hand held monitoring 
device (shown in FIG. 18b). 
The blood oxygen perfusion monitoring and control module 200 is surgically 
implanted in a patient where it is employed to measure, control, monitor, 
and report measured hemoglobin oxygen saturation and tissue perfusion. As 
shown in FIG. 13b, measured blood oxygen is represented as the amount of 
oxygen delivered to the blood on a pulse by pulse basis as the blood is 
pumped by the heart. The amount of blood oxygen delivered to the body can 
be represented according the following formula: 
EQU O.sub.2 (Delivered)=* Hb * SaO.sub.2 * 1.39+PaO.sub.2 * 0.0031, 
where, 
C.O.=Cardiac Output=Heart rate.times.stroke volume liters/mn, 
Hb=Hemoglobin concentration mg/dl, 
SaO.sub.2 =Hemoglobin oxygen saturation %, 
1.39=a constant representing 1.39 ml of oxygen bound to one gram of 
Hemoglobin, 
PaO.sub.2 =partial pressure of oxygen dissolved in plasma, and 
0.0031=a constant representing the amount of oxygen dissolved in plasma. 
The blood oxygen is measured as an estimate of oxygen according to the 
pulsatile perfusion of the blood through a vascular interface. It is to be 
understood that the vascular interface can be, but is not limited to, an 
artery, a vein, a vascular membrane, or vascular tissue. The oxygen 
measurement is acquired according to standard pulse oximetry described 
above. In a preferred embodiment of the present invention, oxygen is 
measured by the implanted control module 300 and at least one paired 
sensor assembly 330 (shown in FIG. 13c). 
FIG. 13c illustrates an embodiment of the sensor assembly 330 assembly 
similar to those shown in FIGS. 7, 10 and 12. However, the two halves 310 
and 320 have linearly arrayed elements that are spaced apart by a distance 
defined by a vascular membrane 340. The linear arrays are paired together 
to form a plurality of paired arrays as may be required to acquire a 
plethysmographic representation of the pulsatile flow of oxygenated and 
reduced hemoglobin passing through the vascular membrane 340. A single 
paired array is required to produce a plethysmograph as shown in FIG. 13b, 
and, multiple arrays, are required to measure a velocity of the pulse 
wave. 
In the embodiment of sensor 330 illustrated in FIGS. 13c, the optical 
sources and optical detectors may be infrared (IR) sources and IR 
detectors, although radiation from infrared through the visible spectrum 
may be employed without departing from the invention. In the figures, 
individual IR sources 310a-d and individual IR detectors 320a-d are 
grouped together in pairs forming the paired array 330. A plurality of 
paired arrays will also comprise an plurality of IR sources and IR 
detectors respectively. The individual IR sources 310a-d may be miniature 
infrared diodes located, in the illustrated embodiment, on one side of the 
vascular membrane 340. IR sources 310a-d are driven by signals generated 
in the control module 300 and transmitted to the IR sources 310a-d via 
conductors (not shown). Similarly, output signals from individual 
detectors 320a-d are transmitted to the control module 300 via separate 
conductors (not shown). 
Each IR source 310 and detector 320 may have associated with it an optical 
filter (not shown) or a time based or encoded discriminator (not shown) 
for selectively emitting and detecting the selected bands of radiation 
emitted for detecting blood oxygen saturation. 
With this embodiment, the IR sources 310 and detectors 320 are arranged 
diametrically opposite each other to detect light transmitted through the 
vascular membrane 340. 
It is important to note that, although this embodiment of the invention is 
described using a single array of paired IR sources and associated 
detectors, that precise configuration is not crucial to the invention. In 
fact, the invention may be implemented, for example, using a plurality of 
paired arrays for detecting reflected, scattered, and transmitted IR 
radiation. 
FIG. 13d shows a plethysmographic representation of pulsatile blood oxygen 
perfusion when four paired arrays are employed. 
The implanted control module 300 preferably incorporates a pulse oximeter 
module (not shown) for producing perfusion data (as shown in FIG. 13d). 
Also incorporated in the control module 300 is a processor module (not 
shown) for analyzing the perfusion data and for producing a control signal 
that is communicated by the control module 300 to a blood oxygen 
regulating device such as, but not limited to, a pacemaker or 
defibrillator. 
FIG. 14 is an illustration of a preferred aspect of the invention showing a 
control module 300 having a sensor 330 for measuring perfusion data to 
determine the level of blood oxygen. The sensor 330 as explained above 
employs at least two selected bands of frequencies to produce detected 
signals corresponding to oxygenated hemoglobin levels which are analyzed 
by the processor module (not shown) of the control module 300. 
The control module 300 also incorporates a communication module (not shown) 
for communicating control information to an implanted pacemaker 360. The 
pacemaker 360, in response to the control information received from the 
control module 300, regulates the heart 1000 (shown for illustrative 
purposes) to pump blood as required to produce a desired blood oxygen 
level. The control module 300 controls blood oxygen by regulating the 
pacemaker to control heart rate and timing of atrial and ventricular 
contraction according to stored blood oxygen values programmed into the 
control module 300. Programmed blood oxygen values are stored in the 
control module 300 through its communication module. An extracorporeal 
communication device (shown in FIG. 18a) is used to control and calibrate 
the control module 300 which is explained in detail below. 
FIG. 15a is an illustration of another preferred aspect of the invention 
showing a control module 300 having a sensor 330 for measuring perfusion 
data to estimate quantity of blood delivered per beat to the tissues. The 
control module 300 incorporates a communication module (not shown) for 
communicating control information to an implanted defibrillator 380. The 
defibrillator 380, in response to the control information from the control 
module 300 and its own internal EKG system 381 (shown for illustrative 
purposes) will regulate the heart 1000 (shown for illustrative purposes) 
to prevent inappropriate in other words the discharge of the internal 
defribulator. 
It is known that an internal defibrillator will at times inappropriately 
defibrillate irregular heart beat patterns. When this occurs the level of 
blood oxygen can be severally affected. To prevent this condition, the 
level of blood oxygen measured by the control module 300 is used to 
confirm proper heart function. Because the control module 300 and sensor 
330 use photo-plethysmography to measure pulsatile perfusion, actual 
defibrillation can be detected as an instantaneous loss of blood oxygen. 
In FIG. 15a the electrical activity of the heart normal sinusrhythm with 
satisfactory tissue perfusion and oxygenation noted on the plethysmography 
waveform. As the trace pressures the cardiac rhythm degenerates into 
ventricular tachycardia and then ventricular fibrillation. The tissue 
perfusion and oxygenation also deteriorates such that pulsatile flow is 
lost. 
FIG. 15b represents a continuation of the ventricular fibrillation trace 
and lack of pulsatile tissue bound flow at timex. The internal 
defibrillation produces an electrical shock that converts the cardiac 
rhythm to normal with satisfactory pulsatile tissue blood flow. 
FIG. 15a illustrates vascular tissue plethysmography with a simultaneous 
and EKG recording of the heart. Therefore, the use of perfusion data to 
control blood oxygen by preventing cardiac defibrillation is a very 
important feature of the invention. This feature provides increased 
assurance that blood oxygen will be maintained consistently without 
disruptions caused by inappropriate heart fibrillation. 
Specific Blood Constituent Monitoring, Control and Reporting System 
Naturally, it should be understood that, although embodiments using 
different groupings of sources and detectors have been described for the 
measurement and control of blood glucose and blood oxygen, the invention 
is not in any way limited to either a specific number of source/detector 
groupings or blood constituents, nor is it absolutely necessary that the 
sources and detectors be arranged in specific configurations. 
FIGS. 16a is a schematic representation of an infrared sensor 330 and its 
control module 300 equipped with a communication module (not shown) 
according to a another preferred embodiment of the present invention. The 
control module 300 and sensor 330 are implanted into the body 
subcutaneously just below the skin. The sensor 330 is placed about a vein, 
an artery or inserted into vascular tissue allowing it to measure and 
control selected blood constituents. The control module 300 through its 
communication module can communicate the measured level of blood 
constituent extracorporeally by means of its communication module to 
devices such as, but not limited to, an external monitoring and warning 
device, or a telecommunication network. 
FIG. 16b is a schematic representation of the infrared sensor 330 shown in 
FIG. 16a used to measure and control a medicinal blood constituent such as 
an antibiotic which is used to treat a localized infection 392 (shown for 
illustrative purposes). It is to be understood that this invention is not 
limited to this embodiment, but may be used to deliver, measure and 
control any medicinal blood constituent such as, but not limited to, 
chemotherapy and cardiac medications. In addition, the measured level of 
medication in the blood can be monitored extracorporeally by a monitoring 
device or provide to a remote location by means of an external 
communication system adapted to a telecommunication network. 
In addition, to controlling blood constituents, the sensor 330 and control 
device 300 can be used to measure and report blood constituent levels 
extracorporeally to remote monitoring equipment. For example, blood 
constituents such as tumor markers including, but not limited to, prostate 
specific antigen (PSA) for detecting prostate cancer and colon embryonic 
antigen (CEA) for detecting colon cancer, can be continuously monitored 
safely and conveniently without the need and inconvenience of constantly 
drawing blood and laboratory testing. By measuring these tumor markers on 
a daily basis, recurrence of tumor will be detected early prior to spread 
throughout the body. This can be accomplished by selecting the appropriate 
optical sensors and detector and operating bandwidths for interaction with 
each specific blood constituent. 
For example and as explained above, blood oxygen can be measured through 
oxygenated hemoglobin with two pairs of sensors and detectors operating at 
660 nanometers and 940 nanometers for detecting oxygenated and reduced 
hemoglobin. 
Implantable Optic Sensor Interface (IOSI) 
FIG. 17a is a schematic representation of an infrared sensor 1330 according 
to another preferred embodiment of the present invention. The sensor 1330 
is shaped like a tuning fork and is implanted surgically into vascular 
tissue. The shape facilitates insertion and retention into vascular rich 
tissue such as a muscle or vascular membrane as shown in FIGS. 17b and 
17c. The sensor has two parallel arms 1320 joined at one end and separated 
from each other by a fixed distance. Each arm has a pointed tip 1332 at 
its other end for piercing the tissue. As the sensor is inserted into the 
tissue a vascular interface 1334 is formed between the arms 1310,1320. The 
arms 1310,1320 have at least one electromagnetically sensitive array 
comprising optical sources and detectors for illuminating the vascular 
interface 1340 and detecting a desired blood constituent described above. 
FIG. 18a is an illustration of an extracorporeal calibration and 
communication module 410. FIG. 18b is an illustration of a hand held 
monitor, display and communication unit 450 for use in connection with 
implantable blood constituent sensors and control modules described above. 
The calibration and control module 410 communicates with a communication 
module (not shown) associated with the implanted control module 300, 
providing calibration data and extracorporeal display and reporting of the 
measured data produced by the control module 300. 
The extracorporeal calibration and communication module 410 communicates 
calibration data directly to the implanted control module 300 allowing 
precise calibration of the measurements made by the control module 300 and 
its sensor 330. Calibration data is produced by the extracorporeal 
calibration and communication module 410 by commercially available methods 
such as glucose oxidase reagent strips 420. 
The communication module 410 and the control module 300 are equipped with 
commercially available communication means adapted for intercorporeal 
communication. 
FIG. 18c is a functional block diagram showing the operation of an 
implantable device according to the invention in communication with the 
extracorporeal calibration and communication module shown in FIG. 18a. 
Extracorporeal Calibration and Communication Modules 
As already noted, processor/pump module 16 contains an electronic 
microprocessor and associated electronic circuitry for generating signals 
to and processing signals from sensor assembly 14 and for generating 
control signals to the insulin pump itself. The microprocessor is 
preferably programmed to execute algorithms to perform multispectral 
correlation, and matched digital bandpass filtering to remove low 
frequency bias and high frequency noise. Such algorithms are well-known to 
those skilled in the art, and need not be described in detail. Moreover, 
the invention is not limited to any specific algorithm; rather, any 
algorithms suitable for performing the desired multispectral correlation 
and filtering functions may be used without departing from the invention. 
It should also be noted that, while the present invention provides 
accurate glucose level measurements, accurate measurement is not crucial 
to the control of the insulin pump 16. In a manner similar to the way a 
house thermostat operates, the pump 16 can be controlled to release a 
fixed quantity of insulin until the glucose levels falls below a 
preselected level. Thus, any algorithm capable of such control is within 
the scope of the invention. The algorithm may also control insulin pump 16 
to release a glucagon bolus, (1 mg of glucagon, when blood glucose levels 
trend below 60 mg/dl will increase the blood glucose level above 150 
mg/dl). 
Processor/pump module 16 may also contain a telemetry transmitter to 
transmit sensor data to an external processor and external insulin pump. 
Insulin can be injected subcutaneously or into a subcutaneous infusaport 
for delivery into the peritoneal cavity or into a portal vein. 
Processor/pump module 16 may also consist of a telemetry receiver for 
external calibration. If recalibration is necessary, the system 10 may be 
recalibrated externally by comparison to a weekly or monthly finger stick 
blood glucose measurement, such as, for example, using calorimetric assay 
of a glucose oxidase/hydrogen peroxide reaction using standard techniques. 
The absolute glucose amount from the external calibration measurement can 
then be telemetered to the processor for calibration. 
Alternatively, each source of radiation may consist of multiple discrete 
bands of light with a unique temporal or frequency modulation, allowing 
discrimination of the different spectral bands. 
Alternatively to providing a narrow band filter for each detector, the 
different spectral bands from the sources are each modulated in a unique 
temporal or frequency fashion, allowing for discrimination of the 
different spectral regions and obviating the need for narrow band filters. 
In another embodiment, source 310a (or 310b, 310c, or 310d) may consist of 
multiple LEDs or multiple laser diodes, each of a different wavelength 
spaced identically collinear or spaced very closely so that each 
wavelength has substantially the identical optical path and interacts with 
substantially identical tissue. The detector 320a, b, c, or d detects 
light from each individual wavelength from source 320a, b, c, or d, 
respectively. 
The processor discriminates amongst the different wavelengths by having 
each wavelength pulse at a different frequency or at a different time. As 
the processor can discriminate amongst the different wavelengths by either 
different frequency or temporal information, narrow wavelength filters 
46a. 48a, and 50a are unnecessary in this embodiment. Multiple sources and 
multiple detectors provide redundancy or alternatively the ability to 
measure different chemical species, although in many cases a single source 
and detector is adequate. The operation of the sensor is otherwise the 
same as described in the previous embodiment. 
Fourier Transform Infrared Spectroscopy (FTIR) Analysis 
Using commercially available Fourier transform infrared spectroscopy (FTIR) 
analysis, it is possible to correlate the sensor output data with blood 
glucose levels, blood fatty acid levels, and blood amino acid levels. 
The present invention may be embodied in other specific forms without 
departing from the spirit or essential attributes thereof and, 
accordingly, reference should be made to the appended claims, rather than 
to the foregoing specification, as indicating the scope of the invention.