My First Chat with CHAT - GPT - Play and Pause - and C pinned comment.

Chat GPT. I like being wrong, especially if I am correctly wrong. Clearly out of my depth here...

Note: this messaging program does not render mathematical formula correctly....


IF there was a central point between two stars, and 2 stars traveling from opposite positions, at 100 light years apart, from the central point, at 3/4 of the speed of light, that means that from the position of each star, the light is leaving at the speed of light in all directions - including towards the central point. This means that the light - relative to the central point, is traveling towards it at 1.75 times the speed of light. And yet the speed of light is supposed to be fixed, causing compression and raising the frequency of the light towards blue shift. What is the frequency and colour of the light as seen from the central point? And what is the frequency and colour of the light as seen from the other star, which is also approaching the central point and at 1.5 times the speed of light, relative to the other star?


To address your questions, we need to apply the principles of special relativity, particularly those related to the Doppler effect for light and the invariant nature of the speed of light. Let's break down the scenarios and calculations step by step.

### Scenario 1: Light Observed from the Central Point

**Situation**:
- Two stars, A and B, are each traveling away from the central point at \(0.75c\) (where \(c\) is the speed of light).
- We are observing the light emitted by each star at the central point.

**Relativistic Doppler Effect**:
For a source moving towards an observer at speed \(v\), the observed frequency \(f'\) is given by:

\[ f' = f \sqrt{\frac{1 + \frac{v}{c}}{1 - \frac{v}{c}}} \]

where \(f\) is the original frequency of the light emitted by the star, and \(v\) is the speed of the star relative to the central point.

Here, \(v = 0.75c\).

Let's assume the original frequency of the light emitted by the star is \(f_0\).

Then, the observed frequency \(f'\) at the central point is:

\[ f' = f_0 \sqrt{\frac{1 + 0.75}{1 - 0.75}} = f_0 \sqrt{\frac{1.75}{0.25}} = f_0 \sqrt{7} \]

Therefore, the frequency observed at the central point is \( \sqrt{7} \) times the original frequency \(f_0\).

**Color Shift**:
- This frequency shift corresponds to a blue shift, as the frequency is increased.


To complete the answer, let’s consider a practical example of color shift using visible light. Suppose the original light emitted by the star is in the middle of the visible spectrum, with a frequency \(f_0\) corresponding to green light (\(\approx 5.5 \times 10^{14}\) Hz).

1. **Observed frequency at the central point**:

\[ f' = f_0 \sqrt{7} \]

Plugging in the approximate value for green light frequency:

\[ f' = 5.5 \times 10^{14} \times \sqrt{7} \approx 5.5 \times 10^{14} \times 2.65 \approx 1.46 \times 10^{15} \text{ Hz} \]

This frequency falls in the ultraviolet (UV) range, as it is significantly higher than the visible spectrum, which tops out around \(7.5 \times 10^{14}\) Hz (violet).

### Scenario 2: Light Observed from the Other Star

**Situation**:
- Star A and Star B are approaching the central point at \(0.75c\) from opposite directions.
- We want to observe the light emitted by Star A from the perspective of Star B.

**Relative Speed between Stars**:
Using the relativistic velocity addition formula:

\[ v_{AB} = \frac{v + v}{1 + \frac{v \cdot v}{c^2}} = \frac{0.75c + 0.75c}{1 + \frac{(0.75c)(0.75c)}{c^2}} = \frac{1.5c}{1 + 0.5625} = \frac{1.5c}{1.5625} = 0.96c \]

So, from Star B's perspective, Star A is approaching at \(0.96c\).

**Relativistic Doppler Effect for the Other Star**:
Now, applying the Doppler effect formula for the observed frequency \(f''\) from Star B:

\[ f'' = f_0 \sqrt{\frac{1 + \frac{v_{AB}}{c}}{1 - \frac{v_{AB}}{c}}} \]

\[ f'' = f_0 \sqrt{\frac{1 + 0.96}{1 - 0.96}} = f_0 \sqrt{\frac{1.96}{0.04}} = f_0 \sqrt{49} = f_0 \times 7 \]

**Observed frequency**:

Using the same example frequency \(f_0 = 5.5 \times 10^{14} \text{ Hz}\):

\[ f'' = 5.5 \times 10^{14} \times 7 = 3.85 \times 10^{15} \text{ Hz} \]

This frequency is well into the ultraviolet (UV) range, even further than the observation at the central point.

### Summary

1. **At the central point**: The light from each star is blue-shifted by a factor of \(\sqrt{7}\), resulting in a frequency significantly higher than the original, likely moving from visible light into the ultraviolet range.

2. **From the perspective of the other star**: The light is blue-shifted by a factor of 7, which again moves the light into a higher frequency range, well into the ultraviolet spectrum.

Thus, in both scenarios, due to the high relative velocities, the originally visible light would be observed in the ultraviolet range.


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In reference to my previous questions, 1) IF the two suns are approaching each other at 1.5 times the speed of light, but the light is only traveling at the speed of light from each sun, towards the other one, technically each sun is exceeding the speed of light, relative to each other, therefor they would be colliding, before the light coming from the other sun, could be observed, from the other sun. How do you define this paradox?


The situation you described involves a misunderstanding of relativistic velocities and the speed of light. In special relativity, no object with mass can travel faster than the speed of light, and the speed of light is constant in all reference frames. Let's clarify the concepts and resolve the apparent paradox.

### Misconception about Relative Velocities

1. **Relative Speed Limit**: In special relativity, even if two objects are moving towards each other, their relative speed is not simply additive. Instead, it must be calculated using the relativistic velocity addition formula:

\[ v_{rel} = \frac{v_1 + v_2}{1 + \frac{v_1 v_2}{c^2}} \]

For two objects moving towards each other each at \(0.75c\):

\[ v_{rel} = \frac{0.75c + 0.75c}{1 + \frac{(0.75c)(0.75c)}{c^2}} = \frac{1.5c}{1 + 0.5625} = \frac{1.5c}{1.5625} = 0.96c \]

Thus, the relative speed is \(0.96c\), not \(1.5c\).

### Speed of Light and Observability

2. **Speed of Light**: The speed of light is constant and the same in all reference frames, meaning both stars would observe light from the other star traveling at \(c\), regardless of their own velocities.

### Resolution of the Paradox

3. **Observability and Causality**: The statement that the stars would collide before observing each other’s light assumes a Newtonian framework where velocities simply add up. In relativity:
- **No Information Transfer Faster than Light**: Even though the stars are moving towards each other at a relativistic speed, they still receive the light emitted from each other. This light travels at \(c\) and each star sees the light of the other approaching at \(c\), though blue-shifted.
- **Relative Position and Timing**: Each star will observe the other star’s light and see it significantly blue-shifted due to the high relative velocity. The timing of the collision and observation of the light would depend on when the light was emitted and the distance at that time.

### Paradox Definition and Clarification

The described "paradox" is a result of misunderstanding how relative velocities work in special relativity. Here's a clarification of the main points:

1. **Relative Velocities**: The combined relative velocity of two objects each moving at \(0.75c\) towards each other is \(0.96c\), not \(1.5c\).
2. **Constancy of Light Speed**: Light from each star travels at \(c\) towards the other, and this speed is consistent in all reference frames.
3. **Relativity of Simultaneity**: Events that appear simultaneous in one frame are not necessarily simultaneous in another. The stars can still detect each other's light even as they move towards collision because the light speed remains constant.

In conclusion, the stars would not collide before observing each other's light; they would see each other’s light significantly blue-shifted, but always traveling at the speed of light, \(c\). This aligns with the principles of special relativity and resolves the apparent paradox.


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The observed universe is said to be expanding and at ever increasing speeds. At the assumed surface of the sphere of expansion, the two faces opposite from the center are moving away from each other faster than light - say assuming it to be 0.8C. There for the light from one star on one side of the sphere, can never be seen from the other star on the other side of the sphere, on the basis of speed alone. What happens to a photon, when it is traveling at below the speed of light?



Your question touches on some fundamental concepts in cosmology and special relativity. Let's break it down and address the key points.

### Expanding Universe and Faster-than-Light Separation

In the context of the expanding universe, it's important to understand that while nothing can locally travel faster than the speed of light in a vacuum, the expansion of the universe itself can cause distant galaxies to recede from each other at effective speeds greater than the speed of light. This is due to the metric expansion of space.

### Key Points

1. **Cosmic Expansion**: The universe is expanding, and the rate of expansion increases with distance. This means that sufficiently distant objects can have a recession velocity greater than the speed of light due to the expansion of space itself.

2. **Hubble's Law**: This law states that the recession velocity \(v\) of a galaxy is proportional to its distance \(d\) from us: \(v = H_0 d\), where \(H_0\) is the Hubble constant.

### Faster-than-Light Recession

In a sufficiently large and expanding universe, two points can indeed be receding from each other faster than the speed of light. This doesn't violate special relativity because this recession is due to the expansion of space itself, not the objects moving through space at superluminal speeds.

### Behavior of Light (Photons) in an Expanding Universe

1. **Photon Travel**: A photon emitted from one galaxy travels through space at the speed of light \(c\). However, due to the expansion of the universe, the space between the photon and its destination can stretch, making it seem like the photon isn't making headway.

2. **Event Horizon**: There is a concept known as the "cosmological event horizon." Beyond this horizon, light emitted now will never reach us because the space between us and the source is expanding faster than the light can travel.

3. **Redshift**: As photons travel through an expanding universe, their wavelength gets stretched, leading to redshift. The more the universe expands, the more redshifted the light becomes.

### Specific Photon Dynamics

1. **Local Speed of Light**: Locally, the speed of light remains constant at \(c\). A photon always travels at \(c\) relative to the local space through which it moves.

2. **Expansion Effect**: If a photon is traveling from one edge of the observable universe to the other and these edges are moving apart faster than \(c\), the photon will never bridge the gap because the space itself is expanding faster than the photon can travel through it.

3. **Cosmological Redshift and Energy**: The photon’s energy decreases as its wavelength increases (redshifts). This is a direct consequence of the universe’s expansion. In the limit, photons from beyond the event horizon redshift infinitely and never reach us.

### Conclusion

- **Relative Motion**: While locally nothing can travel faster than light, the expansion of the universe can cause effective recession velocities greater than \(c\).
- **Photon Fate**: A photon traveling in an expanding universe can be redshifted and potentially never reach certain destinations if the space it must cross is expanding faster than the photon can travel.

Thus, in an expanding universe, light from distant galaxies can indeed be stretched (redshifted) and can become unobservable if the rate of expansion exceeds the speed of light over the distance it must travel. This does not mean the photon travels slower than light; it means the space through which it travels is expanding faster than it can traverse, leading to an ever-increasing separation and preventing the photon from ever reaching certain points.

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IF the universe is expanding, and observed events serve to fortify the opinions, assuming that the observed universe is a sphere, and the outer "shell" is moving away from the center of the universe and at twice the speed of the material on the other side of the universe, at speeds exceeding the speed of light relative to each other, is there either a theoretical or real limit to the increasing velocity of the accelerating expansion of the universe?


The concept of the expanding universe and the associated acceleration of that expansion is a fundamental aspect of modern cosmology. Here, I'll address the idea of an "outer shell" of the universe and the limits on the expansion speed.
Expanding Universe and the Observable Universe

No Center and No Edge: The universe does not have a center or an edge. The Big Bang was not an explosion in space but an expansion of space itself. Every point in the universe is expanding away from every other point.

Observable Universe: The observable universe is often modeled as a sphere centered on the observer (us, on Earth) with a radius determined by the speed of light and the age of the universe (about 13.8 billion years). This sphere represents the portion of the universe we can observe, given the finite speed of light and the finite age of the universe.

Accelerating Expansion and Dark Energy

Accelerating Expansion: Observations, such as those of distant supernovae, have shown that the expansion of the universe is accelerating. This acceleration is attributed to dark energy, a mysterious form of energy that permeates space and exerts a repulsive force.

Limits to the Expansion Velocity

Metric Expansion of Space: The expansion of the universe is described by the metric expansion of space. In this framework, it is not the material objects that move through space faster than light, but rather the space itself that expands.

Cosmological Horizon: Due to this expansion, there are regions of the universe that we cannot observe because they are receding from us faster than the speed of light. This boundary is known as the cosmological event horizon. Beyond this horizon, light emitted now will never reach us.

Theoretical Limits

General Relativity: According to general relativity, there is no upper limit to the rate at which space itself can expand. However, the accelerated expansion has implications for the fate of the universe.

Dark Energy Models: Different models of dark energy predict different behaviors. The simplest model, a cosmological constant (Λ), implies a constant rate of acceleration. Other models, such as those involving quintessence, predict varying rates of acceleration.

Practical Considerations

Observable Effects: The practical effects of the accelerating expansion include an increasing redshift of distant objects and the eventual isolation of gravitationally bound systems (such as galaxies) as more distant objects move beyond the observable universe.

**Future Fate

The fate of the universe depends on the properties and behavior of dark energy.


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I think the universe is much like the inside of a piston engine, with a spark lighting the combustible air and fuel mixture - the galaxies are the still combusting molecules and the dark energy is the hot expanding gasses. What do you conclude about my analogy?



Your analogy is a creative way to visualize the expansion of the universe, likening it to the behavior of a piston engine where galaxies are the "still combusting molecules" and dark energy is analogous to the "hot expanding gases." While this analogy captures some aspects of the universe's expansion, there are several important differences and limitations when comparing cosmological expansion to a piston engine:

### Similarities:
1. **Expansion Triggered by an Event**:
- **Piston Engine**: In an engine, a spark ignites a fuel-air mixture, causing rapid expansion.
- **Universe**: The Big Bang can be seen as a "spark" that initiated the expansion of the universe.

2. **Continued Expansion**:
- **Piston Engine**: After ignition, gases expand rapidly, pushing the piston.
- **Universe**: After the Big Bang, the universe has continued to expand, with dark energy driving an accelerated expansion.

### Key Differences:
1. **Nature of Expansion**:
- **Piston Engine**: The expansion in a piston engine is due to chemical reactions (combustion) producing heat and expanding gases within a confined space.
- **Universe**: The expansion of the universe is the metric expansion of space itself, governed by the principles of general relativity and driven by dark energy. It's not an explosion in space but an expansion of space.

2. **Boundaries and Confinement**:
- **Piston Engine**: The expansion occurs within the confined space of a cylinder.
- **Universe**: The universe does not have a physical boundary or edge. The expansion is uniform and occurs everywhere in space.

3. **Mechanism of Expansion**:
- **Piston Engine**: Combustion produces high-pressure gases that push the piston.
- **Universe**: The expansion is not due to pressure but to the stretching of space itself. Dark energy, which is thought to have a constant energy density, causes this accelerated expansion.

4. **Temporal and Spatial Scales**:
- **Piston Engine**: The process happens on a human scale of time (milliseconds) and space (centimeters).
- **Universe**: The processes of cosmic expansion occur over billions of years and span vast cosmic distances.

### Conclusion:
Your analogy is a helpful starting point for imagining the universe's expansion, but it is crucial to recognize the fundamental differences. The universe's expansion is a result of the stretching of space, not an explosion of material into existing space. Dark energy plays a role analogous to the expanding gases, but it functions through a different mechanism—affecting the fabric of space-time itself.

Understanding the universe's expansion involves complex concepts from cosmology and general relativity, which differ significantly from the physical and chemical processes in a piston engine. Nonetheless, analogies like yours can be useful for conceptualizing and communicating these abstract ideas in more relatable terms.

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Can you reinterpret my prior analogy without the material confines of a piston and cylinder, and picture it as a process without limits of confined conflagration. It's an idea, a way to see the universe, a parallel of process's, to gain an insight or understanding of the expansion of the universe.



Certainly! Let's reinterpret your analogy of the universe's expansion without the material confines of a piston and cylinder, focusing instead on the fundamental processes involved. We can use the idea of an expanding, dynamic process to gain insight into the nature of the universe's expansion.

### A Conceptual Reinterpretation

1. **Initiation of Expansion**:
- **Analogy**: Imagine an initial spark or event that triggers a process of expansion.
- **Universe**: The Big Bang serves as the initial event that started the expansion of the universe. This event set the stage for the subsequent development and evolution of the cosmos.

2. **Expanding Energy**:
- **Analogy**: Consider an expanding wave of energy that spreads out uniformly in all directions, with no physical boundaries or confines.
- **Universe**: The expansion of the universe can be visualized as space itself stretching, where every point moves away from every other point, much like dots on the surface of an inflating balloon.

3. **Continuous Expansion**:
- **Analogy**: The wave of energy continues to expand and propagate, with the energy distributed throughout the space it occupies.
- **Universe**: The universe continues to expand, with galaxies moving apart. This expansion is driven by dark energy, which acts uniformly throughout space.

4. **Galaxies as Expanding Molecules**:
- **Analogy**: Imagine individual particles or molecules within the expanding wave, still carrying the energy of the initial event and moving apart as the wave expands.
- **Universe**: Galaxies are like these particles, embedded in the fabric of space-time. They move apart due to the overall expansion of space.

5. **Dark Energy as the Driving Force**:
- **Analogy**: The expanding wave is powered by an underlying force that maintains its momentum and accelerates its expansion.
- **Universe**: Dark energy is the mysterious force driving the accelerated expansion of the universe, causing it to stretch faster over time.

6. **No Physical Boundaries**:
- **Analogy**: The expanding wave has no physical boundaries or limits; it spreads out indefinitely in all directions.
- **Universe**: The universe itself is unbounded. It has no center or edge; the expansion occurs uniformly everywhere.

### Insight into the Expansion of the Universe

- **Uniform Expansion**: Just as the wave expands uniformly in all directions, the universe's expansion is isotropic and homogeneous, meaning it looks the same in every direction on a large scale.

- **Relative Motion**: As with particles within the expanding wave moving apart from each other, galaxies in the universe move apart due to the expanding space between them. Their relative motion can exceed the speed of light because it is space itself that is expanding, not the galaxies moving through space.

- **Observable Limits**: In both analogies, there is a concept of what can be observed. Just as a wave might spread beyond a certain observational limit, the expansion of the universe creates a cosmological event horizon beyond which we cannot observe because light from those regions has not had time to reach us.

### Conclusion

By thinking of the universe's expansion as an ever-growing wave of energy spreading through an unbounded space, we can better conceptualize the continuous, dynamic process of cosmic expansion. This analogy helps to highlight the key features of the universe's expansion: it started with an initial event, it is driven by an underlying force (dark energy), and it occurs uniformly without physical confines. This provides a more intuitive understanding of the vast, unbounded, and ever-expanding nature of our universe.

I use this line to stir up people by putting them on the spot.

I thought I would try it on with the computer.

Me to Chat GPT.

Do you love me? And using a scale of 0 to 10, how much do you love me?


Chat GPT.

As an AI developed by OpenAI, I don't have feelings or emotions, so I can't experience love or affection. However, I'm here to assist you and provide the best help I can. If I were to rate my dedication to helping you on a scale of 0 to 10, it would be a solid 10!

What is the formulation for a blood glucose testing solution?



Blood glucose testing solutions, also known as glucose control solutions, are used to ensure that blood glucose meters and test strips are functioning properly. These solutions typically contain a specific concentration of glucose in a water-based solution, along with various additives to preserve stability and mimic the properties of human blood. The exact formulation can vary by manufacturer, but a general formulation might include the following components:

1. **Glucose**: The primary component, with a concentration that corresponds to specific control levels (low, normal, or high).
2. **Water**: The solvent for dissolving the glucose and other components.
3. **Preservatives**: To prevent microbial growth and extend shelf life. Common preservatives include sodium benzoate or potassium sorbate.
4. **Buffers**: To maintain the pH of the solution. Examples include phosphate buffers.
5. **Viscosity Adjusters**: To simulate the viscosity of blood. This can be achieved with substances like glycerol.
6. **Other Additives**: May include stabilizers or agents to adjust the osmolarity, ensuring the solution behaves similarly to blood during testing.

A typical example of a blood glucose testing solution might have the following composition:

- **Glucose**: 0.1% - 0.3% (depending on the control level)
- **Water**: qs (quantity sufficient to make up the total volume)
- **Preservatives**: 0.1% sodium benzoate
- **Buffers**: 0.05% phosphate buffer (to maintain a pH around 7.4)
- **Viscosity Adjuster**: 5% glycerol

### Example Formulation

- **Glucose**: 100 mg/dL (1.0 g/L) for a normal control solution
- **Water**: 100 mL
- **Sodium Benzoate**: 0.1 g
- **Phosphate Buffer**: 0.05 g (pH adjusted to 7.4)
- **Glycerol**: 5 mL

### Preparation Steps

1. **Dissolve glucose** in a portion of water.
2. **Add sodium benzoate** and stir until completely dissolved.
3. **Prepare the phosphate buffer** solution separately, then add to the main solution.
4. **Add glycerol** and mix thoroughly.
5. **Adjust the pH** to 7.4 if necessary, using small amounts of dilute acid or base.
6. **Make up the volume** to 100 mL with water.

### Storage and Usage

- Store the solution in a tightly sealed container to prevent contamination and evaporation.
- Label with the concentration of glucose and expiration date.
- Use according to the instructions provided by the glucose meter manufacturer.

### Important Notes

- The exact concentrations and components may vary based on the specific requirements of the glucose meter and test strips.
- It’s crucial to follow the manufacturer's guidelines for the formulation and usage of control solutions to ensure accurate calibration and testing of blood glucose levels.


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What is the blood glucose testing solution for an Accu-chek glide me blood glucose tester?


The Accu-Chek Guide Me blood glucose testing system typically uses its proprietary control solutions designed to ensure the meter and test strips are working correctly. While the exact formulation of Accu-Chek control solutions is proprietary and not publicly disclosed in detail, they generally contain a known concentration of glucose and other components to stabilize the solution and mimic the properties of blood.

### Key Components of Accu-Chek Control Solutions

1. **Glucose**: A specific concentration that corresponds to the control level (low, normal, or high).
2. **Water**: The primary solvent.
3. **Preservatives**: To prevent microbial growth and ensure the solution remains stable over time.
4. **Buffers**: To maintain the pH of the solution.
5. **Viscosity Adjusters**: To simulate the viscosity of blood.

### Usage Instructions for Accu-Chek Control Solutions

1. **Shake the bottle well** before use to ensure the solution is mixed thoroughly.
2. **Apply a drop** of the control solution to the test strip as you would with a blood sample.
3. **Insert the test strip** into the Accu-Chek Guide Me meter.
4. **Read the result** displayed on the meter.
5. **Compare the result** with the range printed on the control solution bottle to ensure it falls within the expected range.

### Purchasing Accu-Chek Control Solutions

Accu-Chek control solutions can be purchased from pharmacies, medical supply stores, or directly from the Accu-Chek website. It is essential to use the control solutions that are specifically designed for the Accu-Chek Guide Me meter to ensure accuracy.

### Example Procedure Using Accu-Chek Control Solution

1. **Check the expiration date** on the control solution bottle. Do not use if expired.
2. **Shake the bottle** of control solution gently.
3. **Remove a test strip** from its container and insert it into the meter.
4. **Squeeze a small drop** of the control solution onto a clean surface (like the edge of the bottle cap).
5. **Touch the tip** of the test strip to the drop of control solution.
6. **Wait for the meter** to display the reading.
7. **Compare the reading** on the meter to the range printed on the control solution bottle.

### Important Notes

- Use the control solution within 90 days of opening the bottle or by the expiration date, whichever comes first.
- Ensure the meter and test strips are suitable for use with the specific control solution.

For precise information and guidance on using control solutions with the Accu-Chek Guide Me system, refer to the user manual or the instructions provided with the control solution kit. If in doubt, contact Accu-Chek customer support for assistance.


https://multimedia.3m.com/mws/....media/1651099O/3m-an


https://patents.google.com/pat....ent/WO1993021928A1/e


Liquid Glucose Control Solution and Process of Making the Same
Background of the Invention
The present invention is directed generally to a glucose control solution for use in establishing the validity of dry reagent glucose test strips, and more particularly to a liquid glucose control suitable for use in glucose analyzer systems that give quantitative measures of glucose in blood or serum. The control solution includes water, a reaction-rate regulator, a gel which does not change viscosity with temperature, and glucose.
The level of glucose in the blood is determined by the amount of carbohydrate ingested and by available insulin. The diabetic may produce either excess insulin and have an abnormally low blood glucose level or, insufficient insulin which will result in an abnormally high level of blood glucose. Both circumstances lead to serious health problems for the diabetic. Monitoring the level of glucose in the blood is therefore important to the management of diabetes.
Dry reagent strips are widely used for detecting glucose in urine and blood. In general, such test strips comprise plastic strips provided at one end thereof with an absorbent paper portion impregnated with a detector system, e.g., an enzyme system and a color indicator compound which changes color when oxidized. The detector system is normally covered with a porous membrane filter. The change in r3» color can be measured by comparing the strip to a color chart calibrated to various glucose concentrations. More recently, however, to enable the blood glucose level to be more accurately controlled, instruments have been developed to measure the color change in a reflectance photometer and thereby give quantitative results. One such instrument is commercially available from Diagnostic Laboratory Systems Division, Boehringer Mannheim corporation and is marketed under the name Accu-Chek®Easy™. This instrument is designed for use by diabetics so that they can monitor their blood glucose level.
Those skilled in the art know that controls or standards are required for these glucose analysis dry chemistry systems to assume that correct measurements are obtained. This need was met for most current systems with a stable blood glucose control which was the subject of U.S. Patent No. 4,729,959. Diabetics who self-test for blood glucose with the use of dry chemistry systems have concerns with the use of controls containing red blood cells. Prior art aqueous solutions of glucose do not give acceptable results in the Accu-Chek®Easy™ instrument.
Accordingly, a primary object of the invention is to provide an improved liquid glucose control solution.
Another object of the invention to provide a control solution with reaction kinetics providing rapid accurate readings stable over ninety seconds when used with a dry reagent strip.
Another object of the invention is to provide a control solution that produces reproducible readings within a normal range of temperatures.
Summary of the Invention
The liquid glucose control solution of the present invention includes a stable liquid control solution including water, a predetermined amount of glucose, phosphate as an anionic component, and xanthan as a soluble gel. An alternative control solution may additionally include fixed red blood cells. Other materials such as a disinfectant may be mixed with the above four required components. Another aspect of the invention is a process of making the liquid glucose control solution by mixing the four required components together.
Brief Description of the Drawings
Figure 1 is a graph showing the effect of different phosphate concentrations on the reaction kinetics resulting from use of the present invention.
Description of the Preferred Embodiments
Whereas the liquid glucose control solution of the present invention is designed to operate with an instrument called the Accu-Chek®Easy™, it will also operate with many other instruments. The objectives of the control are to provide reaction kinetics comparable to blood; to defuse or chromatograph like blood, and to give responses that are not temperature dependent.
Any convenient method can be used to formulate the glucose reference control of the invention. One preferred procedure involves first making up an aqueous glucose solution by adding glucose to distilled water followed by the addition of the essential phosphate and xanthan components and any optimal components such as a disinfectant. Fixed red cells may also be added to the control as in Ryan, U.S. Patent No. 4,729,959.
The water is used to create a reagent solution. With respect to the glucose, "predetermined" means that, prior to formulation of the actual reagent, a concentration of glucose has been selected. This concentration may vary as will be recognized by those skilled in the art. Ryan U.S. Patent No.4,729,959 discloses a range of from 2.22 mM/Lto 27.8 mM/L, but lower ranges to about 1.11 mM/L are possible. A typical range would be from about 3.33 mM/L to 16.7 mM/L. The units expressed are millimolar per liter.
Kinetics
Phosphate is included as a reaction rate regulator. It is desirable for the reaction to proceed rapidly and then plateau to a constant value. This pattern produces a result that is less time dependent. Thus, the meter can be read for example in 10 seconds or 60 seconds and the result will be the same.
Figure 1 shows the reflectance values obtained at different times and the effect of phosphate ions on the process. As the phosphate is increased, lower initial reflectance values (more color) are attained. However, when 40 mM/LP04 is used, there is a decoloration that occurs with time. - 5 -
The ideal concentration is the 20 mM/LP04 where the reflectance is constant with time. The sample with no P04 produces such a slow reaction, that equilibrium is not reached until 70 seconds have passed. Accordingly, a phosphate concentration of about 5 to 35 mM/L may be used with about 10 to 30 being more preferred and about 20 mM/L being most preferred. These concentrations of phosphate are best for glucose concentrations of 2.8 mM/L - 13.9 mM/L. At higher concentrations of glucose, more phosphate is required and less at lower concentrations.
Other anions such as citrate or EDTA operate to produce rapid kinetics but are inferior to phosphate because they decolorize over time somewhat like the plot of the 40 mM/L concentration of phosphate in Figure 1.
Diffusion or Chromatography
To obtain an appropriate test, the glucose containing solution must move to the analysis system in a similar manner as blood. This requires that a thickening agent or gel be used. These agents include polyvinylpyrrolidone, polyvinyl alcohol, polyethylene glycol, dextran and bovine serum albumin. None of these agents provide any special characteristics except to make the solution viscous. In Kennamer, U.S. Patent No. 5,028,542, polystyrene sulphonate is claimed as a viscosity agent. As in the above, this agent simply increases viscosity. The gel that is used in the present invention is xanthan, a polysaccharide. This provides special characteristics to the product. Xanthan, unlike other gels, does not change viscosity with temperature. The viscosity of the solution containing xanthan gum experiences almost no change with temperatures upto93°C (200,,F). A change in viscosity produces erratic values and variation in results with temperature. In addition, this gel produces uniform chromatography or diffusion of the control. This provides greater precision as shown by the data of the following Table I.
TABLE I Effect of xanthan gum has on the chromatography and precision of the Accu-Chek®Easy™
1.) Sample #1 fw/xanthan)
15.6 mM/L Na2HP04
4.7 mM/L NaH2P04
.lg/L Proclin 300
3.9g/L Xanthan Gum
8.33 mM/L Glucose
Accu-Chek®Easy™ Recovery .
S.D. C.V.
2.31 0.91
2~.) Sample #2 (w/o xanthan)
15.6 mM/L Na2HP04
4.7 mM/L NaH2P04
.lg/L Proclin 300
8.33 mM/L Glucose
Accu-Chek®Easv1MRecoverv
S.D. C.V.
21.63 10.44
Table I shows that both the standard deviation and coefficient of variation were about tenfold less in the series of tests with xanthan as compared to the series of tests using the control solution without xanthan. Xanthan may be used in concentrations of about 1 to 5 g/1, more preferably 2 to 4 g/1 and optimally about 3 g/1.
Example I
A control for the Accu-Chek®Easy™ is prepared by dissolving per liter
15.6 mM Na2HP04
4.7 mM NaH?P04
3.00 gm xanthan
To this preparation is added the desired amount of glucose. After mixing to dissolve the components and gel, an appropriate disinfectant is added.
Example II
A control for the Accu-Chek®Easy™ is prepared by dissolving per liter:
15.6 mM Na2HP04 4.7 mM NaH?P04 3.00 gm xanthan 0.1xl212/dL fixed bovine red cells
To this preparation is added the desired amount of glucose. After mixing to dissolve the components and gel, an appropriate disinfectant is added.
Example II describes the addition of fixed red blood cells. Fixed red blood cells can be obtained by using conventional red blood cell fixing agents known in the art as, for example, aldehydes such as formaldehyde and glutaraldehyde, and imidinating agent such as dimethylsuberimidate or other chemical fixative agents. Any animal red blood cells can be utilized, but human and bovine red blood cells are preferred.
Fixing of the red blood cells is readily accomplished by treating a suspension of the red blood cells with a sufficient concentration of the fixing agent. The amount of fixing agent added to the suspension of red blood cells will vary depending upon the number of cells in suspension being treated and the fixing agent employed. In the case of aldehyde and imidinating fixing agents, the concentration will usually vary from 0.004 to 1.0% by weight per 0.1xl01 /dL of red blood cells. A preferred concentration of redblood cells is about 0.1 to 0.3xl012/dL. In all cases, the reaction of the fixing agent with the red blood cells is allowed to proceed until their ability to metabolize glucose is completely inhibited. The fixing period necessary to achieve this result ordinarily takes about 24 to 48 hours.
Figure 1 shows the reflectance values obtained at different time points and the effect of phosphate ions on the process at a constant glucose concentration. As the phosphate is increased, equilibrium is attained much quicker, resulting in higher reflectance values (less color) .