Wednesday, October 20, 2010

The Race to Develop a Painless Blood Glucose Monitor

Hopes are high for alternatives to finger sticks, but so are the technological hurdles.

If blood sugar were better controlled, the complications associated with diabetes might be far less prevalent and far less severe. Yet the average insulin-dependent diabetic exerts relatively poor control, injecting insulin just twice daily, despite conclusive evidence that three to four precisely measured administrations of insulin daily could prevent long-term complications, such as blindness.

The pain and inconvenience of current blood glucose tests, which require finger sticks with lancets to draw blood for analysis on personal glucose monitors, are one reason that the average insulin-dependent diabetic administers the hormone twice a day. But help may be on the way.

Entrepreneurs are racing to develop the ultimate expression of biosensor technology--a fast, painless, and convenient means for testing blood glucose. Ultimately, such a monitor could be tied into an implantable insulin pump that would deliver exact amounts of insulin to the patient. Adequate control could reduce--even eliminate for some patients--complications that impose some $45 billion in health-care costs annually in the United States alone.

In the process, companies making these monitors could reap an impressive financial harvest. Industry sources estimate that the worldwide market for glucose-monitoring products surpassed $1.5 billion in 1994 and continues to grow at a 14% clip annually. Of that market, U.S. sales make up about 59% of total revenues.

About 90% of the total sales today are related to disposable glucose reagent strips for finger stick monitoring. Painless monitors could take away a substantial portion of those sales. "Given the size of the market, anyone who can come up with a viable noninvasive or painless technique is going to make a lot of money," says Gregory Faris, an analyst at SRI International (Menlo Park, CA).

MiniMed's flexible glucose sensor is housed in a tube for subcutaneous placement using a needle introducer.

Faris notes that there has been a virtually endless stream of ideas driving entrepreneurs, including tests using samples of tears, saliva, and urine; an optical technique that scans the eye; and technologies for shining infrared or laser light into and through the body. "It’s easy to mislead yourself that you can do it," Faris says. Several companies do, however, appear to be making significant progress.

Cygnus, Inc. (Redwood City, CA), has developed several prototypes of its GlucoWatch, a wrist-worn device that promises to noninvasively monitor glucose levels. The watchlike instrument would use electroosmosis to draw glucose molecules from the patient’s skin into a dermal patch, whose contents would be measured and the data interpreted by an integrated circuit.

SpectRx (Norcross, GA) is developing a handheld device that uses a laser to create a micropore about the width of a human hair in the outer, dead layer of skin from which interstitial fluid is collected. This fluid is then measured using off-the-shelf glucose test strip chemistry. Integ (St. Paul, MN) is designing a device that would use a small needle to penetrate the skin and gain a sample of interstitial fluid containing glucose. A handheld battery-operated infrared photometer would then measure the glucose in the sample.


But amid the hopes for developing a painless glucose monitor are stories such as that of Futrex Medical Instrumentation, Inc. (Gaithersburg, MD). For years, the firm showcased its DreamBeam, a battery-operated box about the size of a television remote control designed to provide noninvasive glucose measurements with the use of infrared radiation. Last September, the Securities and Exchange Commission (SEC) filed a fraud action alleging that Futrex and its senior officer, Robert D. Rosenthal, made false claims to investors in connection with a $1.85 million private placement of debt securities. The SEC alleges that the company and Rosenthal knowingly deceived investors, presenting false conclusions from clinical studies. During at least one meeting with investors, Rosenthal used the device on himself, and claimed the readings were accurate. But according to the SEC, he allegedly had "directed a Futrex employee to program a DreamBeam to function as if it were giving a glucose reading." Rosenthal was not available to MD&DI for comment.

The Futrex incident has not quelled hopes that a painless glucose monitor can be built. "There’s a rich array of technologies supporting biosensor R&D," says Cort Wrotnowski, principal of the consulting firm Amvir Associates (Greenwich, CT), which specializes in the assessment of biosensor technology. "Somewhere there is an answer for what these guys want to do."

Several big names in the medical industry agree. Becton Dickinson (Franklin Lakes, NJ) and Yamanouchi Pharmaceutical (Tokyo, Japan) have signed on to market products under development by Cygnus. Yamanouchi bought marketing and distribution rights for Japan and Korea; Becton Dickinson bought them for the rest of the world. Similarly, Abbott Laboratories (Abbott Park, IL) purchased exclusive worldwide rights to SpectRx technology except in Singapore and the Netherlands, where the company has coexclusive rights.

The leaders in the race to develop a painless glucose monitor are taking either of two tacks. One is the use of infrared--or near infrared -- technology to noninvasively obtain optical signatures indicating the level of glucose. The other collects samples of interstitial fluid for analysis.


Infrared analysis is as tantalizing as it is difficult to achieve. "Infrared can penetrate the skin, so measurements are possible at different depths," says biosensor consultant Wrotnowski. "But the feedback can be extremely complex, which means you need very sophisticated mathematical methods to do the analysis." The complexity of the data is a result of the way infrared interacts with aqueous solutions. Water soluble substances absorb infrared radiation very strongly, he explains, returning a "very messy signal." Ironically, nonaqueous substances return a much better signal. "These guys are trying to make something useful out of what constitutes infrared’s greatest weakness," he says.

Ominously, the Futrex DreamBeam supposedly was based on infrared technology that could measure blood glucose levels by passing infrared light through a finger. The SEC complaint against Futrex states that studies of an earlier prototype, the Futrex 9000, as well as a version of the DreamBeam were unsuccessful and that a field study conducted in 1995 with the DreamBeam generated useless results, allegedly because of a manufacturing defect.

Another light-based technology, the Diasensor 1000 by Biocontrol Technologies (Pittsburgh) has had its share of problems. The tabletop spectrophotometer is designed to recognize a person’s glucose patterns through the use of a light beam that passes through the skin of the forearm into the blood and is then reflected back to a sensor. A microprocessor is intended to interpret the data and calculate the blood glucose level.

Early last year enthusiasm was running high that FDA would soon clear the Diasensor 1000. But an advisory panel in February 1996 recommended against approval. At the meeting, the company produced successful data on only eight patients in its clinical trials, despite enrolling 85. Twenty-two were eliminated due to malfunction of the machine; two were eliminated because glucose levels did not vary sufficiently to calibrate the machine to them. Of the remaining 61 patients, 47 had the machine successfully calibrated to them. The company chose to follow 23 of them for 30 days, and FDA did not object, according to the company. The eight successes were found among those 23 subjects.

In an open letter to stockholders and diabetics, CEO Fred E. Cooper defended the company’s position that eight patients provided sufficient data on efficacy and safety: "It was enough because for those eight patients, 263 data points...were submitted to FDA--that’s an average of 32 data points per patient. Firms currently using finger stick technology only submit an average of one data point per patient for devices they are attempting to get cleared. That means 100 data points submitted equals 100 patients studied. Therefore, 263 data points submitted for the Diasensor 1000 is equal to having tested 263 patients--a substantial test size."

In the 10 months following the panel meeting, Biocontrol withdrew, revised, resubmitted, and then withdrew again a 510(k) application for the device. The company is continuing to work toward FDA clearance of the Diasensor 1000, says company spokesperson Susan Taylor, "and we are going to keep working at it." Company officials are now trying to finalize the details for a new study to be conducted in the homes of subjects. When completed, Biocontrol expects to submit a newly revised application to FDA.

Descriptions of the Diasensor 1000 published by the company refer only to "optics, electronics, and detection subsystems; software; and algorithms." Details about the device are not released by the company due to the competitive nature of the industry, says Taylor, who will state only that the device uses "a near infrared spectrum."

Cygnus's GlucoWatch uses electroosmosis to draw glucose molecules from the skin into a dermal patch for analysis.

Whereas Biocontrol Technologies is trying to use light radiation to non-invasively probe the patient, Integ’s LifeGuide System uses a small needle to sample interstitial fluid in the upper layer of the skin. "We do not puncture the skin; we go into the dermal layer," says Dave Talen, Integ marketing manager. "The dermal layer has very few capillaries and very few nerve endings, so when the needle probes only to that depth, you don’t draw blood and you don’t feel pain, in the traditional sense." Pushing the device, which is about the size of a large cellular phone, against the skin forces the fluid into a "read" window positioned between an infrared source and a detector. "The glucose molecules absorb a certain amount of the energy and we measure that absorbence," Talen says. Clinical trials are expected to begin in summer.


The SpectRx system also samples interstitial fluid but rather than use a needle, the device fires a laser into the skin, creating a micropore approximately 80 µm across and 20 µm deep. The interstitial fluid that flows into the micropore is sampled and then passed to a test strip analyzer now on the market for conventional finger stick blood glucose testing. SpectRx spokesperson Bill Wells refused to provide more details about the device or its stage of development, noting that "we have developed a handheld prototype that successfully creates micropores." In some subjects, Wells says, the interstitial fluid rushes into the micropore quite readily. "In other people, it has to be coaxed out," he says. "There are some enhancements that are part of the development process that allow us to collect the fluid."

The analysis is much more straightforward than the collection process. As a result of its alliance with Abbott, the company is integrating Abbott’s MediSense test strip technology into the device. According to SpectRx, preliminary tests have shown a high correlation between glucose in the interstitial fluid and in blood.

MiniMed (Sylmar, CA) is working on a minimally invasive monitor that would use a small flexible probe to sample interstitial fluid from the subcutaneous tissue between the skin and muscle. The probe is inserted using a needle and then the needle is removed. "There is a temporary immediate pain, the same as you would get from an injection," says John Mastrototaro, director of sensor development at MiniMed. The probe would be replaced with a new one after three or four days to prevent undue irritation and the risk of infection, he says. A sensor in the probe analyzes the fluid for glucose content, passing the data via cable to a microprocessor that might be worn on the belt like a pager. Early models might not provide a quantitative readout of glucose levels, but rather be programmed to emit an alarm if glucose levels exceed a certain range. "If it detects that the glucose is low, an alarm would signal the patient to do a finger stick to determine the glucose level," Mastrototaro explains.

Feasibility studies involving 12 to 20 insulin-dependent diabetics are under way. A trial involving up to 50 subjects is scheduled for midyear.

MiniMed is currently a leading manufacturer of external insulin pumps, holding about 75% of the U.S. market for those pumps. The company has also developed an implantable pump being sold in Europe. Ultimately, an automatic glucose sensor capable of delivering precise glucose measurements might be integrated with a version of the pump. "We have the delivery device; the next step is closing the loop by creating a sensor that will automatically tell the pump how much insulin to deliver and when," says Jim Berg, a MiniMed spokesperson. "That is our grand design--to create an artificial pancreas."

Cygnus, Inc., advocates a noninvasive approach that leverages electroosmosis to obtain interstitial fluid. "When exposed to this low-level electrical energy, charged particles in the interstitial fluid pull the fluid out of the skin and the glucose molecules go along for the ride," explains Craig Carlson, Cygnus vice president for corporate marketing and strategic planning. A small disposable pad, constructed from proprietary material, located between the GlucoWatch hardware and patient skin collects the glucose molecules. Those molecules trigger an electrochemical reaction with a reagent in the GlucoPad, thereby generating an electric current. A sensor in the GlucoWatch measures the resultant current and an application-specific integrated circuit (ASIC) calculates the glucose in the patient’s blood.

Levels are calculated automatically at set times throughout the day and night. At the push of a button, those calculations are displayed on the watch dial in the context of trends in glucose levels. Alarms would be designed to go off if the levels exceed specific limits. An electronic memory also would allow downloading of the data to a computer for long-term trend analysis, potentially helpful in managing the disease. "We see ourselves not so much as providing glucose measurements as information managers," Carlson says.


Common to all developers is the challenge of providing accurate blood glucose measurements, regardless of such variables as patient exercise and the digestion of different kinds of foods. The approach that is being taken by most companies, including MiniMed, is to control for these variables by testing subjects under different conditions and then modifying the device to render accurate measurements.

Each of the companies have other specific challenges to overcome. The invasive nature of the MiniMed device, minimal though it is, presents the danger of skewing data. "If the sensor causes a lot of irritation or trauma at the site of insertion, it can cause the local glucose concentration to change," Mastrototaro says. "Another possible problem is that proteins in the body could foul the sensor or impair its performance."

Noninvasive infrared technology presents special challenges because skin and bone absorb and deflect light. There is the added problem of trying to iden-tify optical signatures of glucose levels, signatures that may be as specific to patients as fingerprints. Therefore these devices may have to be calibrated to individual users.

Calibration proved to be a problem for Biocontrol in its clinical study presented to the FDA advisory panel last year. Other companies have been able to avoid that hurdle. SpectRx, for example, uses an off-the-shelf test strip technology provided by Abbott. "It certainly shortens the development time to use existing technology," Wells says.

Cygnus officials believe their technology has no serious technical challenges ahead. But the company must contend with the pitfalls of being a device integrator. "The task we have now is making sure all of the components that have been optimized and tweaked since the early prototype testing operate effectively as a unit," Carlson says.

Cygnus, whose strength is in the design of transdermal patches, most notably the mass-marketed Nicotrol patch, must rely on contract engineering firms to build hardware for doing the analysis and providing the readings. The pitfalls of such an arrangement became obvious in November 1996 when Cygnus announced that a change in the ASIC that serves as the brains of GlucoWatch would delay delivery of the latest prototype and, consequently, clinical trials. The problem, according to Carlson, was a defect in the design of the chip. "Two wires were touching one another," he says. "So when the chip was put in place, there was a short." At press time, it appeared that a reengineered ASIC would soon be delivered and integrated into the latest prototype.

Cygnus executives have shunned media attention, partly because of the highly competitive nature of the industry, Carlson says, but also because hopes have been unduly raised by competitors. Company policy, he explains, is to make a viable product and then seek publicity --not the other way around. MiniMed has a similar policy. "People’s lives are involved and we don’t want to suggest that this technology is right around the corner," says MiniMed spokesperson Berg. "This is very tricky, difficult work."

Greg Freiherr is a contributing editor to MD&DI.

Monday, October 18, 2010

Glucose sensors

continuous glucose monitoring system

There are currently three CGMS (continuous glucose monitoring system) available. The first is Medtronic's Minimed Paradigm RTS with a sub-cutaneous probe attached to a small transmitter (roughly the size of a quarter) that sends interstitial glucose levels to a small pager sized receiver every five minutes. As well, the DexCom STS System is available (2Q 2006). It is a hypodermic probe with a small transmitter. The receiver is about the size of a cell phone and can operate up to five feet from the transmitter. Aside from a two-hour calibration period, monitoring is logged at five-minute intervals for up to 72 hours. The user can set the high and low glucose alarms. The third CGMS available is the FreeStyle Navigator from Abbott Laboratories.

There is currently an effort to develop an integrated treatment system with a glucose meter, insulin pump, and wristop controller, as well as an effort to integrate the glucose meter and a cell phone. These glucose meter/cellular phone combinations are under testing and currently cost $149 USD retail. Testing strips are proprietary and available only through the manufacturer (no insurance availability). These "Glugophones" are currently offered in three forms: as a dongle for the iPhone, an add-on pack for LG model UX5000, VX5200, and LX350 cell phones, as well as an add-on pack for the Motorola Razr cell phone. This limits providers to AT&T for the iPhone and Verizon for the others. Similar systems have been tested for a longer time in Finland.

Recent advances in cellular data communications technology have enabled the development of glucose meters that directly integrate cellular data transmission capability, enabling the user to both transmit glucose data to the medical caregiver and receive direct guidance from the caregiver on the screen of the glucose meter. The first such device, from Telcare, Inc., was exhibited at the 2010 CTIA International Wireless Expo[10], where it won an E-Tech award. This device is currently undergoing clinical testing in the US and Internationally.

Sunday, October 17, 2010

Monitoring Diabetes Without Pain and Blood: Biosensors Offer New Alternatives

A daily regimen of pricked fingers and blood tests is an essential part of life for someone living with diabetes.

Monitoring blood glucose levels can be tiresome, even with today’s improved monitoring devices. Drs. Mak Paranjape and John Currie, researchers in the Georgetown Advanced Electronics Laboratory (GAEL), are working to take the process to a whole new level.

For the past few years, the team has been developing and testing a new biosensor device for blood glucose monitoring. The size of a small bandaid, it is designed to be worn anywhere on the body, where the biosensor samples tiny amounts of fluids that lie just beneath the skin. The device is small and convenient, and makes measuring glucose levels pain-free and noninvasive.

How is this device possible on such a small scale without puncturing the skin? Imagine the human skin as if it were a large frozen body of water, like the Tidal Basin in Washington DC, in December. Under the top layer of thin ice would be water, just like the glucose-rich interstitial fluids just underneath the skin. Traditional blood monitoring uses a needle to make a (relatively) large, deep hole to extract blood droplets from the capillaries, which lie deeper under the skin surface. In the analogy with the frozen Tidal Basin, the blood vessels would lie on the bottom of the lake. The needle in this device might be analogous to the Washington Monument, creating a very large hole through the ice. Painful, indeed!

The new bio-sensor, however, makes possible a different, painless approach. Instead of puncturing a “big” hole into the skin, the bio-sensor works by making tiny pores in the skin, through which the interstitial fluid can rise. This would be similar to melting a very small region in the ice to access the water below.

The biosensor device works to painlessly remove this outer-dermis, or dead-skin layer, by using a “micro-hotplate” (or micro-heater), which measures about 50 microns square and is carefully controlled to apply a small amount of power. (To imagine how small this area is, note that the period at the end of this sentence is about 10 times larger than the hotplate). For 30 milliseconds (that’s 30 one-thousandths of a second) the “hotplate” is turned on to a temperature of 130 C. Sounds hot, but in such a small spot, and for such a short time, a person cannot even detect the heat, or feel any pain, as it is applied to the outer layers of skin.

This hotplate causes a tiny micro-pore to form through which a little bubble of fluid passively emerges. The bio-sensor then reads the glucose levels in the sample fluid through tiny electrodes coated with a substance that reacts specifically to the glucose.

The bio-sensor project initially began through funding from the military, with the intention of developing a miniature device to remotely monitor the health status of soldiers in a battlefield. This tiny prototype chip, which acts as a patch on the skin and is called the B-FIT (Bio-Flips Integrable Transdermal MicroSystem), can obtain samples of fluid from under the skin one time every hour for a 24-hour period.

To support the design and development of the device, Currie and Paranjape received a Department of Defense contract for $3 million over 3 years from DARPA (Defense Advanced Research Projects Agency).

In this application, troops being sent onto a battlefield could be fitted with biosensors. A medic in a central location could monitor significant changes in biomolecular levels, using a PDA or similar device, assessing for injuries or exposure to biological or chemical warfare agents. If the medic detected dangerous changes in a soldier’s body chemistry, the soldier could be removed from the field for medical care.

In the miniaturized world of micro- and nano-technology, novel measuring devices are possible, with multiple applications for health monitoring. Combining technical capabilities available through places like GAEL with biomedical research knowledge and a keen imagination opens many new doors. Dr. Paranjape and his colleagues in the Physics department are at the forefront of these new discoveries.

Friday, October 15, 2010

Gluco band

preview of glcose level depend on color code is in the following link

Friday, October 8, 2010

Glucose Sensors

Glucose Sensors

Three glucose sensors were developed based on different technology platforms:

• a classical amperometric sensor using thick film technology;

• a fibre-optic fluorometric glucose sensor based on oxygen measurement, and

• a spectroscopic glucose sensor using mid-infrared spectroscopy

Amperometric glucose sensor

An enzymatic-electrochemical sensor was developed for continuous glucose monitoring based on a novel miniaturized planar sensor flow-through cell arrangement. The sensor, which was manufactured using polymer thick film technology, features four electrodes serving as the amperometric detection unit and for measuring conductivity.

The enzyme is immobilized by a hydrogel matrix forming a self-adhesive layer at the surface of the working electrode. The electrode surfaces and the enzyme immobilisate are protected against interfering bio-compounds from the body fluid by a biocompatible selective diffusion barrier (molecular weight 160 kDa). The polymer coating improved the linearity range of the glucose sensor to 20 mM and the drift during long-term glucose measurements in serum solution was limited to +0.23 % per hour. The response time of the sensor is about 3 min and the running-in period is less than 10 minutes.

A plastic foil was micro-structured by hot embossing and glued to the sensor to create a disposable flow-through cell. The patented inner geometry of the flow-through cell, featuring a gap close to the indicator window and surrounded by channels for the sample flow, prevents air bubbles from forming or entering the sensitive area of the sensor. This arrangement provides a continuous flow of small volumes of sample to the sensitive area by capillary forces and convection. The volume of the measuring chamber is about 0.3 µl (Fig.1).

Successful in-vivo measurements were carried out using this arrangement in several workshops with healthy volunteers, diabetic patients and critically ill patients after major cardiothoracic surgery.

Successful in-vivo measurements were carried out using this arrangement in several workshops with healthy volunteers, diabetic patients and critically ill patients after major cardiothoracic surgery.

Left side: Fig.1: Disposable glucose sensor flow-through cell arrangement for continuous glucose measurement. Right side: Fig.2: Exemplary temporal glucose profile measured in a type 1 diabetes volunteer at the Clinical Research Center of the Medical University Graz, Austria

Fibre-optic glucose sensor

The fibre-optic sensor system uses the enzyme-based oxidation of glucose, in combination with an optical oxygen sensor as transducer. A fibre-optic dual sensor setup was integrated into a flow-through cell. One sensor measures oxygen sensor only, while the second oxygen sensor is covered with an enzyme (glucose oxidase, GOD) layer. The difference in oxygen concentration between these two sensors is linear up to 15 mM of glucose. The major advantage of this approach is the excellent selectivity of the oxygen optode transducer.

The sensors have already been tested in both clinical studies and intensive care units with very promising results. Improvements of the transducers are currently underway, including the synthesis of new fluorophors with improved properties such as greater brightness and lower temperature dependence.

Fig.a: System for fibre-optic fluorometric glucose measurement using a standard subcutaneous microdialysis system

Spectroscopic glucose sensor

A mid-infrared sensor for continuous glucose monitoring in combination with a subcutaneous or a vascular body interface was developed to meet the demand for reagent-free assays. The sensor is designed to ensure the utmost reliability needed for the intensive care environment. Monitoring of human subcutaneous interstitial fluid or whole blood dialysate was realized by an ex-vivo arrangement. The body interface between the subject and the glucose sensing device was an implantable microdialysis catheter or an extra-corporeal whole blood microdialysis device, respectively. A fluidic system for intermittent sample transport to a flow-through micro-cell was developed for transporting the biofluid sample to a mini-spectrometer. The body fluids were dialysed using perfusates at flow rates of 1 or 5 µl/min, realized by push-pull operation of a mini-peristaltic pump. As a result of the osmotic exchange of biocompounds between the biofluid and the perfusate, low molecular mass components were harvested. The fully automated system was explored for its multi-component capability for glucose, urea, lactate, acetate, bicarbonate, as well as for pCO2 and pH of the biofluid buffer system. Features also include dialysis recovery rate measurements and air bubble detection and removal. The multi-component capability of the system allows acetate of the ELO-MEL perfusate to be used as a suitable marker for the simultaneous determination of the microdialysis recovery rate for accurate estimation of interstitial or whole blood concentrations.

The prototype was tested successfully for online monitoring of blood glucose in healthy and type 1 diabetic subjects including its combination with an insulin pump for closing the loop.

Fig.b: Left side: Glucose concentration profiles of a type 1 diabetic subject monitored continuously using a mid-IR spectrometer and a subcutaneously implanted microdialysis probe (A), and lactate concentrations in the dialysate (B). Right side: Glucose concentration profiles of a type 1 diabetic subject monitored spectrometrically using extra-corporeal whole blood dialysis (C) and dialysis recovery rates using a perfusate marker (D)

Fig.c: Clarke Error Grid plot of sensor predicted glucose and reference blood glucose values from eight type 1 diabetic volunteers using a subcutaneous body interface (A) and from five type 1 diabetic volunteers using a vascular interface (B).

Other metabolite Sensors

The parameters pH, oxygen (O2) and carbon dioxide (CO2) are essential in determining the physiological status of critically ill patients. The limited reliability of continuous intravascular measurements and drawbacks of intermittent blood sampling led the CLINICIP team to develop optical sensors for measuring these parameters in the adipose tissue. The continuous measurement of pH, O2 and CO2 is based on the withdrawal of interstitial fluid from adipose tissue by means of a microdialysis catheter. The interstitial fluid then flows through a microfluidic circuit formed by the catheter arranged in series with optical sensors. While the pH sensor was based on a sensing capillary, the O2 and CO2 sensors were implemented in two forms: a sensing glass capillary and a planar sensing membrane within a flow-through cell.

pH sensor: The pH sensor consists of a glass capillary carrying on its internal wall phenol red covalently bound to the glass. The sensing capillary is inserted in the microfluidic circuit containing the microdialysis catheter used for the extraction of interstitial fluid (Fig.3). The optoelectronic instrument developed for pH interrogation is shown in Fig.4. Two optical fibres are used to couple the sensing capillary with the unit in which a light-emitting diode (LED) and a photodetector are used as source and detector, respectively. The device is controlled by a software program, developed in LabVIEW environment, which acquires the signals and evaluates, displays and stores the data.

In-vivo studies have shown that the adipose tissue seems to be a reliable alternative site for in-vivo continuous monitoring of stress conditions.

Fig.3: Fluidic System for Microdialysis Measurements.

Fig.4: Photo of the System for pH detection

O2 sensor: The oxygen opto-chemical sensor is based on the principle of the luminescence quenching of a fluorophore by collision with oxygen.

The inner surface of the glass capillary is coated with a sensor cocktail of Pt(II)-TFPP dissolved in chloroform. The optoelectronic instrumentation basically consists of a light source (LED emitting at about 517 nm) to excite the luminescence signal, a reference light source and a detection module comprising a Si photodiode and optical filters.

The planar sensing membranes are created by coating a transparent substrate with an oxygen sensitive solution and connecting them to the optoelectronic unit via an optical fibre. The main advantage of this approach is that the optoelectronic instrumentation can be separated from the flow-through cell, thus allowing greater miniaturization than for the capillary based sensor. Its small size makes it more flexible for use in in-vivo experiments and field tests in hospitals.

Fig.d: Measurement system for planar sensing membranes: the flow-through cell has a size of 35x35x12 mm (width x length x heigth) and can allocate one transparent substrate coated with up to 2 sensing spots for two different parameters, e.g. O2 and CO2

CO2 sensor: CO2 measurements are based on the dual luminophore referencing (DLR) approach, an internal ratiometric method for converting the analyte-sensitive fluorescence intensity signal into the frequency-domain or time-domain information by co-immobilizing an inert long-lifetime reference luminophore and a short-lifetime indicator material which responds to CO2 induced pH changes in the membrane.

Measurements involve a sensor cocktail containing Ru(dpp)32+ nanoparticles doped in polyacrilonitrile (PAN) with negligible permeability towards oxygen (to avoid interference from oxygen) and the HPTS(TOA)4 ion pair. This mixture is deposited onto the inner surface of glass capillaries with a needle (capillary sensors) or applied to a solid support (planar sensor membranes). The optoelectronic units used for the interrogation of the CO2 sensing capillary and the planar sensing membrane are the same as described for O2 detection.

The planar sensor membranes are characterised by a better stability in time due to a better adhesion of the sensing film on the solid support and a better reproducibility in terms of realisation.

The three sensors were tested in-vivo.



Tuesday, October 5, 2010

Glucose Phantoms

Phantoms are generally used for vitro measurements of non-invasive blood glucose measurements, they comprises of aqueous solution with water, fat and muscles of animal bodies. In vivo tests for blood sugar monitoring, the human finger web which is normally around 6.5mm is used. so, approximately the same amount of viscous fluid is possible by these glucose phantoms (1).

Phantoms controls the experimental parameters and thereby used for many critical tests on heamoglobin and tissue tumors.

Phospate buffer(0.1 M,pH 7.35) with added fat from animal sources makes the phantom ready for tests provided of having thickness in desired range.

[1]Jason J. Burmeister, Hoeil Chung* and Mark A. Arnoldt, "Phantoms for Noninvasive Blood Glucose Sensing with Near Infrared Transmission Spectroscopy",Photochemistry and Photobiology, 1998, 67(1): 50-55.