Microscope apparatus

Abstract

A microscope apparatus comprising a housing for a lens and a lens, wherein the housing for the lens has a camera facing surface and a light source facing surface, wherein the lens has a light source facing surface and wherein the light source facing surface of the lens is set back from the light source facing surface.

Description

[0001] Microscope Apparatus

[0002] The present invention relates to a microscope apparatus which allows for differential interference contrast imaging using a digital imaging device such as a mobile telephone.

[0003] Differential interference contrast imaging is a microscopy technique that introduces contrast to images of samples, for example bodily fluids such as blood which have little or no contrast when viewed using bright field microscopy.

[0004] Microscopes are expensive but when combined with DIC contrast the set up is beyond the purchasing power of most of the population.

[0005] Live Blood Analysis (LBA) traditionally uses a darkfield microscope with HD video imaging, to visualise live blood cells and plasma using specialised contrast techniques. This is often used in holistic health assessment as a method of simple monitoring metabolic function; however, the technique has a history of divided opinion as to how the information is interpreted. The equipment is expensive, and practitioners require extensive training. Doctors and General Practitioners are not trained to interpret live blood analysis and rely on standardised laboratory blood tests.

[0006] According to the present invention there is provided a microscope apparatus comprising a housing for a lens and a lens, wherein the housing for the lens has a camera facing surface and a light source facing surface, wherein the lens has a light source facing surface and wherein the light source facing surface of the lens is recessed from or set back from the light source facing surface by in the range of about 5pm to about 15pm.

[0007] The microscope apparatus of the present invention allows for DIC quality imaging without the expense of DIC equipment. The recess distance is in relation to the part of the lens which is closest to the light source facing surface of the housing.

[0008] Preferably the apparatus further comprises a light source. Alternatively, natural light can be used. However, the provision of a light source allows for the light path to be directed and for a specific number of lumens to be provided. Preferably the light source is configured to face towards the housing light source facing surface and an emitting area of the light source provides a convergent beam angle in the range of about 6 degrees to about 22 degrees.

[0009] According to a further aspect of the present invention there is provided a microscope apparatus comprising a housing for a lens, a lens and a light source, wherein the housing for the lens has a camera facing surface and a light source facing surface and wherein the lens has a light source facing surface such that the light source is configured to face towards the housing light source facing surface and an emitting area of the light source provides a convergent beam angle in the range of about 6 degrees to about 22 degrees.

[0010] The microscope apparatus of the present invention allows for DIC quality imaging without the expense of DIC equipment.

[0011] Preferably the light source facing surface of the lens is recessed from or set back from the light source facing surface by in the range of about 5pm to about 15pm.

[0012] It has been found that setting the lens back in the housing and, therefore, away from the sample slide at the aforementioned distances provides a sharp image.

[0013] Preferably the light source facing surface of the lens is recessed from or set back from the light source facing surface by in the range of about 7pm to about 13pm.

[0014] Preferably the light source facing surface of the lens is recessed from or set back from the light source facing surface by about 10pm.

[0015] Preferably an emitting area of the light source provides a convergent beam in relation to the lens light source facing surface of an angle in the range of about 10 degrees to about 18 degrees.

[0016] Preferably an emitting area of the light source provides a convergent beam in relation to the lens light source facing surface of an angle of about 14 degrees.

[0017] It has been found that this angle of illumination provides sharp images. Preferably light emitted from the light source is contained and directed towards the lens. If, in use, an area of a sample slide being viewed is shielded from ambient light such that only light from the light source is being used to illuminate the sample then a sharper image is produced.

[0018] Preferably the light source is an LED.

[0019] Preferably, the LED has a round cross-section. Alternatively, the LED has a rectangular crosssection.

[0020] Preferably the light source has a diffuse emitting area of about 1 to about 1.5 square millimetres and emits light at about 3000k to about 4000K while consuming a current of in the range of about 5pA to about 25pA.

[0021] Preferably the light source has a diffuse emitting area of about 1 to about 1.5 square millimetres and emits light at about 3000k to about 4000K while consuming a current of in the range of about lOpA to about 15pA.

[0022] Preferably the light source has a diffuse emitting area of about 1.1 square millimetres and emits light at about 3800k while consuming a current of about 13pA.

[0023] Preferably the distance between the light source and the lens is between about 2.5mm and 4mm, preferably 3.0mm and 3.5mm, preferably 3.5mm.

[0024] Preferably the lens is a micro-spherical ball lens. The benefit of a micro-spherical ball lens is that Total Internal Reflection (TIR) wave optic principles can be used. Preferably the micro- spherical lens is in the range of about 0.35mm to about 0.8mm in diameter, preferably 0.5mm.

[0025] Preferably at least part of a surface of the housing adjacent the lens is opaque and / or reflective. If the lens is at least partly encased in an opaque or reflective surface then at least part of the light being emitted therethrough will undergo TIR. Preferably, the microscope apparatus further comprising a retaining means.

[0026] Preferably the retaining means allows for releasable coupling.

[0027] Preferably the retaining means retains, in use, a sample slide and / or the light source.

[0028] Preferably the sample slide is a pair of thin glass cover slips, for example a standard microscope cover glass. These slips can be made from any suitable material, for example, Quartz or super white glass.

[0029] Preferably wherein the light source comprises the retaining means.

[0030] Preferably the retaining means is a magnet. Use of a magnet as the retaining means is useful if the housing for the lens is made from a magnetic substance such as a suitable stainless steel.

[0031] Preferably the housing is at least partly formed from a magnetic substance.

[0032] Preferably the camera facing surface of the housing comprises a securing means.

[0033] Preferably the securing means allows for releasable coupling.

[0034] Preferably the securing means comprises a tacky film. The tacky film allows the housing to be placed over a digital imaging device such as a camera lens and moved when necessary, either to remove the housing or to reposition it. The tacky film can be removed from the housing when no longer suitably tacky and replaced.

[0035] Preferably the tacky film at least partly covers the camera facing surface of the housing for the lens. In this regard, preferably the tacky film does not cover the lens. The tacky film need only be present in a sufficient amount to ensure secure coupling to a digital imaging device. The tacky film can be provided in several parts or can be provided with an aperture such that at least part of the lens is not covered with the tacky film.

[0036] Preferably the sample slide further comprises a microfluidic device. A microfluidic device such as narrow channels, which can be an integral part of any sample slide, for example, grooves on a glass slip can be used to separate out parts of the sample. The grooves can be of varying thickness. The microfluidic device of the present invention can be operated using finger / thumb pressure or an electric pressure transducer to replicate such pressure.

[0037] The microfluidic device of the present invention can comprise a plurality of channels with substantially identical widths. Alternatively, the microfluidic device of the present invention can comprise a plurality of channels with varying widths. The widths of the channels will be defined by the size of the particles in any sample which is to be sorted. For example, the channels may be between 1pm and 10pm, preferably 3pm to 7pm.

[0038] The plurality of channels can be substantially aligned in a single axis or the channels can extend radially about a substantially circular configuration. Preferably a first channel is provided which is wider than the plurality of second channels. Preferably the first channel is an inlet channel which allows any sample to be sorted into communication with the plurality of second channels. Preferably the communication direction of any sample source can be reversed such that the sample first flows through the plurality of second channels before the first channel.

[0039] Preferably the housing further comprises movement means for, in use, moving a sample slide.

[0040] Preferably the movement means affords movement of the sample slide in an x and / or y axis in a horizontal plane. Using such a movement means will allow the sample slide to be easily manoeuvred into the correct orientation above the digital imaging device. Use of a movement means rather than fingers can result in fine movements of the sample slide as rack and pinion or gears and teeth mechanisms can be used to translate larder movements into fine movements. This can be important if you are viewing a sample which may be sensitive to excess pressure, such as a blood sample which if too much pressure is applied will burst the cells. The movement means may be hand operated or electro / mechanical actuators.

[0041] Preferably the microscope apparatus is configured to be used with a digital imaging device. The use of readily available digital imaging devices means that clear magnified images can be produced without the need for an expensive microscope. The digital imaging device can be used to further magnify a sample and / or focus the lens in the apparatus of the present invention, if necessary. Preferably the digital imaging device is a handheld device. As the microscope apparatus is small and portable, use of a handheld device means that the microscope apparatus can be used anywhere.

[0042] Preferably the digital imaging device is a camera in a mobile telephone. A mobile phone, tablet or camera linked to a computer are ideal devices for use with the digital imaging device as they allow auto-focussing and images taken by the camera can be magnified by varying degrees and stored.

[0043] According to the present invention there is provided a method of using a microscope apparatus according to the present invention, the method comprising: a) placing a sample of bodily fluid on a sample slide; b) placing the camera facing surface of the housing for the lens of the microscope apparatus according to the present invention in cooperative alignment with a digital imaging device; c) placing the sample slide on the light source facing surface of the housing for the lens of the microscope apparatus according to the present invention; d) applying light to the sample slide from a light source; and e) optionally, capturing the image displayed on the digital imaging device.

[0044] Step b can be undertaken before step a).

[0045] Further, optionally, ambient light can be excluded from the sample.

[0046] After placing the sample slide on the housing for the lens the sample slide can be moved either with fingers and / or thumbs of the user or using any movement means provided in the housing. The sample slide should be moved so that any sample provided thereon is positioned above the digital imaging device and below the light source.

[0047] If the housing for the lens is not positioned correctly it can be moved by releasing the connection with the digital imaging device and replacing it in the correct position.

[0048] The invention teaches a method where Differential Interference Contrast (DIC) images are obtained using a Super Micro Lens arrangement where TIR Wave Optics supply the corrective wave form. This provides a profoundly compact arrangement when using the life-time configured light source. The benefit of using a non-invasive capillary pin prick sample from the finger tip as with traditional LBA is maintained, but with superior DIC imaging. This is further enhanced leading to a paradigm shift in hand held diagnostics by incorporating Micro Fluidics. Together they can present unequivocal evidence of metabolic function in various forms. It can also be used for screening as an effective cardio vascular risk assessment device. As cardio vascular disease is the worldwide number one cause of death at 20 million per year, the simple, low cost screening technique (DIC Fluidics) can provide indicators of latent blood pathology in a far wider section of the population.

[0049] With the advent of Artificial Intelligence (Al) diagnostics and data analysis, Al can be used to immediately analyse complex data uploaded to an Al platform. The HD image data can be quickly and accurately analysed, comparing the history of thousands of similar encrypted data streams with the latest diagnostics with complete confidentiality.

[0050] The difference between traditional blood testing and DIC Fluidics is that with traditional medical blood testing, several millilitres of blood are required to drawn within a health care facility, and the preserved blood samples are sent to a laboratory where they are analysed for cell counts and chemical composition which can take several hours to several days.

[0051] With the DIC Fluidics technique, a painless and stress free automatic lancet pin prick is used to provide a tiny blood spot sample, that can be prepared anywhere within seconds and examined immediately - while the blood cells are still behaving as they would within the body. Self monitoring by the patient, while following prescribed protocols and treatment, would also be of great benefit to the patient and healthcare provider alike, particularly as the blood analysis can be performed simply using the device, and digitally record and upload to the Al or other web platform automatically. The inconvenience of appointments and traveling could be avoided, reducing stress and expense and reduce loading on health care facilities.

[0052] When the patient uses the device on a smartphone, the healthcare provider can give guidance to the patient in realtime while they are using the device and see the images at the same time. This allows expert guidance and reassurance when required. More sophisticated detailed blood analysis can be made in situ using micro structures with specialised features. Typically cell count with the ability locally constrain a sample number of blood cells and add an activator or fluorescent / stain media for example through the cover slip and / or measure plasma potential. The ability to quickly and accurately measure change in density can indicate haemoglobin Hb.

[0053] The invention teaches a method of construction and use of Differential Interference Contrast (DIC) imaging for dynamic live blood analysis on a smart phone, iPad or similar device. The data can be processed using an app and the DIC Fluidics data can be uploaded to a diagnostic Al platform. It can also be used in a health care or laboratory environment as a standalone device which can have multiple channels. Using standardised micro structures with Al Pattern Recognition, advanced diagnostics using reactive agents and Fluorescent Fluidics, could be a cost effective addition to Imaging Flow Cytometry.

[0054] In accordance with embodiments, a method for dynamic live blood analysis is provided. The method comprises obtaining Differential Interference Contrast (DIC) images using a DIC imaging system, wherein the DIC imaging system comprises a Super Micro Lens arrangement and TIR Wave Optics to provide a corrective wave form and a compact arrangement. A blood sample is provided using a blood sampling system, wherein the blood sampling system incorporates a painless and stress-free automatic lancet pin prick to obtain the blood sample from a finger tip, and wherein the blood sampling system enhances the DIC imaging and provides the blood sample as a blood spot sample. Complex data is analyzed using an Artificial Intelligence (Al) analysis system, wherein the Al analysis system analyzes the complex data and the complex data uploaded. Image data is analyzed using an image data analysis system, wherein the image data analysis system compares data streams and analyses HD image data. A patient is monitored using a patient monitoring system, wherein the patient monitoring system allows the patient to self-monitor, perform blood analysis, record data, and upload data to follow protocols and treatment. Dynamic live blood analysis is processed and performed using a dynamic live blood analysis system, wherein the dynamic live blood analysis system processes data for the dynamic live blood analysis.

[0055] In accordance with other embodiments, a system for dynamic live blood analysis is provided. The system comprises a Differential Interference Contrast (DIC) imaging system configured to obtain DIC images, wherein the DIC imaging system comprises a Super Micro Lens arrangement and TIR Wave Optics to provide a corrective wave form and a compact arrangement. A blood sampling system is configured to provide a blood sample, wherein the blood sampling system incorporates a painless and stress-free automatic lancet pin prick to obtain the blood sample from a finger tip, and wherein the blood sampling system enhances the DIC imaging and provides the blood sample as a blood spot sample. An Artificial Intelligence (Al) analysis system is configured to complex data, wherein the Al analysis system analyses the complex data and the complex data uploaded. An image data analysis system is configured to analyse image data, wherein the image data analysis system compares data streams and analyses HD image data. A patient monitoring system is configured to monitor a patient, wherein the patient monitoring system allows the patient to self-monitor, perform blood analysis, record data, and upload data to follow protocols and treatment. A dynamic live blood analysis system is configured to process and perform dynamic live blood analysis, wherein the dynamic live blood analysis system processes data for the dynamic live blood analysis.

[0056] In yet other embodiments, the method for dynamic live blood analysis further comprises that the blood cells in the blood sample behave as within a body.

[0057] In yet other embodiments, the method for dynamic live blood analysis further comprises receiving uploaded data by an Al web platform.

[0058] In yet other embodiments, the method for dynamic live blood analysis further comprises providing guidance to the patient and viewing images by a patient guidance system, wherein the patient guidance system is used by the patient and a healthcare provider.

[0059] In yet other embodiments, the method for dynamic live blood analysis further comprises performing detailed blood analysis using a detailed blood analysis system comprising micro structures and specialised features.

[0060] In yet other embodiments, the method for dynamic live blood analysis further comprises adding an activator or fluorescent / stain media using a sample preparation system comprising a cover slip. In yet other embodiments, the method for dynamic live blood analysis further comprises measuring plasma potential using a plasma potential measurement system.

[0061] In yet other embodiments, the method for dynamic live blood analysis further comprises indicating haemoglobin Hb using a haemoglobin Hb indication system based on a change in density.

[0062] In yet other embodiments, the method for dynamic live blood analysis further comprises uploading data to a diagnostic Al platform.

[0063] In yet other embodiments, the method for dynamic live blood analysis further comprises using the method in a standalone device system in a health care environment or a laboratory environment, wherein the standalone device system comprises multiple channels.

[0064] In yet other embodiments, the method for dynamic live blood analysis further comprises using an Al pattern recognition system with standardised micro structures.

[0065] In yet other embodiments, the method for dynamic live blood analysis further comprises using an advanced diagnostics system with reactive agents and Fluorescent Fluidics.

[0066] In yet other embodiments, the method for dynamic live blood analysis further comprises using the method as a cost-effective addition to Imaging Flow Cytometry.

[0067] In yet other embodiments, the system for dynamic live blood analysis further comprises that the blood cells in the blood sample behave as within a body.

[0068] In yet other embodiments, the system for dynamic live blood analysis further comprises an Al web platform configured to receive uploaded data.

[0069] In yet other embodiments, the system for dynamic live blood analysis further comprises a patient guidance system configured to provide guidance to the patient and allow a healthcare provider to view images, wherein the patient guidance system is used by the patient and the healthcare provider. In yet other embodiments, the system for dynamic live blood analysis further comprises a detailed blood analysis system configured to perform detailed blood analysis, wherein the detailed blood analysis system comprises micro structures and specialized features.

[0070] In yet other embodiments, the system for dynamic live blood analysis further comprises a sample preparation system configured to add an activator or fluorescent / stain media, wherein the sample preparation system comprises a cover slip.

[0071] In yet other embodiments, the system for dynamic live blood analysis further comprises a plasma potential measurement system configured to measure plasma potential.

[0072] Within this specification, the term "about" means plus or minus 20%, preferably plus or minus 10%, preferably plus or minus 5%, preferably plus or minus 2%.

[0073] It will be understood that various changes and modification to the present invention described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the present invention and without diminishing its advantages.

[0074] Within this specification embodiments have been described in a way which enables a clear and concise specification to be written, but it is intended and will be appreciated that embodiments may be variously combined or separated without parting from the invention including but not limited to apparatus features relating to method claims.

[0075] The invention will now be described solely by way of example and with reference to the accompanying drawings itemised below:

[0076] Figure la shows a plan view from underneath of housing according to the present invention;

[0077] Figure lb shows a side view of a housing according to the present invention;

[0078] Figure 2 shows an enlarged sectional side view of a housing according to the present invention;

[0079] Figure 3a shows a plan view of a sample slide arrangement;

[0080] Figure 3b shows an enlarge plan view of a microfluidic device;

[0081] Figure 4 shows a plan view of a microscope apparatus with a sample slide in situ; Figure 5 shows a plan view of a microscope apparatus with a sample slide in situ in place on the front of a mobile phone before the slide is viewed;

[0082] Figure 6 shows a plan view of a microscope apparatus with a sample slide in situ in place on the front of a mobile phone viewing the sample;

[0083] Figure 7 shows a plan view of a microscope apparatus with a sample slide in situ in place on the front of a mobile phone viewing the sample interacting with the microfluidic device;

[0084] Figure 8 shows a plan view of a microscope apparatus with a sample slide in situ in place on the front of a mobile phone viewing the sample interacting with the microfluidic device;

[0085] Figure 9a shows a plan view of a cover slip with microfluidic structures guide ring;

[0086] Figure 9b shows a plan view of an enlarged image of a group of microfluidic structures;

[0087] Figure 10a shows a plan view of an enlarged image of a group of microfluidic structures in more detail;

[0088] Figure 10b shows a plan view of an enlarged image of a group of microfluidic structures in more detail;

[0089] Figure 11 shows a plan view of an enlarged image of an alternative arrangement of a group of microfluidic structures;

[0090] Figure 12a shows a plan view of an enlarged image of an alternative arrangement of a group of microfluidic structures;

[0091] Figure 12b shows a side cross section view of the arrangement of a group of microfluidic structures from Figure 12a;

[0092] Figure 13 shows the arrangement of a group of microfluidic structures from Figure 12a, in use;

[0093] Figure 14 shows a plan view of an enlarged image of an alternative arrangement of a group of microfluidic structures;

[0094] Figure 15a shows a sectional view of the housing for the lens with the lens in situ and in position relative to a camera lens. The figure also shows light pathways SI and S2.

[0095] Figure 15b shows a sectional view of the housing for the lens with the lens in situ and in position relative to a camera lens. The figure also shows light pathways SI and S2.

[0096] Figure 16a shows an example of the screen image obtained on a smart phone when light is passed through the lens but there is no sample slide in situ.

[0097] Figure 16b shows an enlarged view of the edge of the optic lens as shown in Figure 16a.

[0098] Figure 17 shows the light energy available at the surface of the lens.

[0099] Figure 18 shows a cross-sectional view of an enclosed light source or light bar in cooperative alignment with a sample slide, lens housing and camera lens.

[0100] Figure 19a shows a side cross-section of the light source / bar. Figure 19b shows a plan view of the light source / bar of Figure 19a from the light producing side.

[0101] Figure 20a shows perspective view of a housing for a lens with a movement means.

[0102] Figure 20b shows a view of the housing for a lens with electrical movement means (not shown) Figure 20c show a view of the stage frame with a movement means in Figure 20a.

[0103] Figure 21a shows a plan line drawing of the housing for a lens with a movement means in Figure 20a.

[0104] Figure 21b shows a side view line drawing of the housing for a lens with a movement means in Figure 20a.

[0105] Figure 21c shows an enlarged side view line drawing of the housing for a lens with a movement means in Figure 20a.

[0106] Figure 22 shows a plan view of a microscope apparatus with a sample slide in situ in place on the front of a mobile phone viewing the sample;

[0107] An embodiment of the present invention is shown in Figure la which shows a relatively thin rectangular plate or housing for a lens 3, which has an aperture (not shown) which has a micro optic or lens 1 therein held in position by a retaining disc 4. The rectangular plate or housing 3 can be formed from any material but preferably it is formed from a stainless steel type 401 or any material capable of attraction by a magnet.

[0108] As shown in Figure lb a double sided adhesive rectangular film or securing means 8 can be employed that has a high-tac adhesive on one side, mounted against the disc or housing 3, and a low-tac adhesive side facing outwards. This outer low tack surface can be covered with a clear adhesive tape to keep it clean and dust free (not shown).

[0109] Figure 2 shows the housing for the lens, which has a camera facing surface 91 and a light source facing surface 92. The micro optic or lens 1, is a micro-spherical lens, held by a retaining disc 4, which can be stepped. The retaining disc 4, can be held in position within the central hole in the rectangular steel plate item 3, by the rear film 8, and the two front films 6, and 9. Suitable apertures are provided in the rear film 8 and two front films 6 and 9 to ensure that the lens 1 is not obscured. The closest surface of lens 1 to the light source facing surface of the housing is recessed from the light source facing surface of the housing 92 by a distance G, which can be between 5pm and 15pm.

[0110] Film 6 can be used for printed graphics, such as instructions or advertising and film 9 can be a protective transparent film with a non-reflective low friction outer surface. Film 9 can be split into two halves about the central micro optic or lens 1. This narrow channel is to allow the optic to be wiped free of dust particles and micro fibres and to allow the necessary spacing to ensure correct focus. A light bar 60 which has a housing for an LED light 56, which has a matt finish to ensure a diffuse light is emitted, that sits over the sample slide 11, 12, 16 is provided in line with the lens 1 and this greatly reduces contamination by micro particulates. The distance D between the light source 56 and the flexible film 11 is 2.5mm to 4mm.

[0111] The LED is configured to have a light emission area E and the convergent beam 63 travels through the lens 1. The convergent beam angle is in the range of 6 degrees to 22 degrees. In other words, the subtended angle ABX created by arc A B and vertex X is in the range of 6 degrees to 22 degrees.

[0112] The light bar 60 has a retaining means or an internal magnet 65, which attracts the light bar to contact the magnetic / steel plate 3, by pivoting around a pivot point or cross pin 70, shown in Figure lb.

[0113] Figure 3a shows a sample slide or coversheet arrangement with a first coversheet 12, with five microstructures or microfluidic devices which are too small to visualise but the position of which are marked by microstructure or microfluidic device guides 14, bonded to a flexible film extension 11, this is supplied together with a second coversheet 16, in one set, and these are held together with a static attraction peel-able blue protective film 10, shown with a dotted outline. This is to keep the (blood) sample surfaces and microstructures from becoming contaminated or damaged through handling.

[0114] The microstructures or microfluidic devices 15 are channels with varying widths.

[0115] The use of a disposable automatic lancet is recommended for obtaining the pin prick of blood from a patient’s finger print pad. The finger print pad must be cleaned immediately before using the lancet with an alcohol wipe, and only the blood spot should touch against the underside centre of coversheet 16, to prevent contamination. The present invention can be used to image other bodily fluids and blood which has previously been sampled.

[0116] In use, the blue film 10, is partly peeled away releasing the contact between the two cover sheets and is used to hold the two coversheets in alignment when the blood sample 22, is placed on the centre of the underside of the coversheet 16.

[0117] The coversheet 16, (shown out of alignment for clarity) now with the blood sample 22 on the underside, can easily be realigned with the cover sheet 12, using the blue film cover. Once aligned, the coversheet 16, is lightly pressed into contact with coversheet 12, the thumb and forefinger can be used to gently press the two coversheets together. They are then effectively bonded together by the hydraulic attraction of the blood sample 22. The blue film 10, can then be peeled away and discarded without disturbing the blood sample 22, between the two coversheets 12, and 16.

[0118] The coversheet 12, is typically silica or quartz glass 0.13 to 0.17mm which is a standard thickness for coversheet of this size. The top surface can have one or more microstructures or microfluidic devices 15, these can be typically lithographic substrates or embossed / UV cast film, bonded to the surface, in this example they are shown in five positions, visible as reference guides. A pin prick sample of blood 22 is transferred to cover the central microstructure. A coversheet 16, typically of silica or quartz glass 0.13 to 0.17mm thick is used to carry the blood sample 22, to the coversheet 12. The microstructure or microfluidic device 15, can be any size or number but are typically 6pm to 10pm thick and prevent the coversheet 12, 16 from crushing the red blood cells which are disc shaped and generally 3pm to 4pm thick. In this embodiment of the present invention the coversheets 12,16 capture and hold still the white blood cells as these are usually spherical and larger than 10pm in diameter and this prevents them from moving with the plasma. The pressure used to spread the blood sample 22, should be sufficient to make the blood sample 22, turn to a transparent film with a light red line around its periphery.

[0119] If the blood sample 22, spreads to the edges of the coverglass 12, 16 then the blood sample spot size was too large. Typically the blood spot on the finger, before transfer to the coverglass, should be 1.0 to 1.5mm in diameter. If smaller than this then the useful sample area is reduced.

[0120] Figure 4 shows the arrangement of the steel plate or housing for a lens 3, coversheets 12, and 16, in position under the light bar 60 and these are held against the steel plate or housing for a lens 3, by the light bar 60, using the internal magnet 65, shown in Figure lb. The microstructures or microfluidic devices 15, can be aligned using the central alignment circle 13, which is printed on the housing 3 using one of the microstructure guide circles 14. Any of the five alignment guide circles items 14, can be aligned with the guide circle 13. The circle alignment system allows any one of the microstructures or microfluidic devices 15, to be centred with the micro optic or lens 1, as the microstructures themselves are so small they invisible to the naked eye.

[0121] Figure 5 shows the steel plate or housing 3, positioned such that the micro optic or lens 1, is aligned with a digital imaging device 5 such a screen camera of a smart phone, iPad or similar device item 20. The steel plate or housing 3, can be held in position using the low tack adhesive film item 8, shown in Figure 2.

[0122] When the digital imaging device or front smart phone camera lens 5 is enabled, the screen 20 will go dark apart from a round patch of light 23 moving on the screen 20. The patch of light 23 is centred in the middle of the screen 20. When the steel plate or housing 3 is lowered onto the digital imaging device or camera lens 5 and the light outer image 21 is in line with the edges on each side of the screen 20 the housing 3 is correctly placed. The steel plate or housing 3 lightly bonds to the surface glass of the screen 20 using a securing means such as the exposed low-tac bond of the adhesive film 8. The housing 3 can be easily repositioned if it is not giving a centred image circle 21. The low-tac adhesive film 8 can be used hundreds of times and can be cleaned or replaced if contaminated.

[0123] Figure 6 shows the coversheet assembly 11,12 and 16 with the blood sample 22, and the microstructure guide ring 14, is mounted slightly off centre of the centre guide ring 13 marked on film 6. The image of the blood sample 22 is then shown on screen 20. The off-centre image of the micro structure item 15 can be simply corrected by slightly moving the coversheet assembly 11,12 and 16, and the image of microstructure 15, will move towards the centre of the image. The movements required are extremely small but this skill is quickly acquired. Figure 7 shows the microstructure 15 centred in the screen image and the microstructure guide ring 14 is concentric with the guide ring 13 printed on the steel plate 3. The light bar 60, is centred over the microstructure guide ring 14.

[0124] Figure 7 further illustrates the dynamic elements of this DIC Fluidics arrangement. On conventional dark field microscopes the image field can be moved around by adjusting the micro stage platform that holds a glass slide with the blood sample encapsulated between the coversheet and the glass slide, the glass slide is secured in place by spring clips. The blood plasma and red blood cells are more or less stationary in this field of plasma but can drift a little as the plasma spreads and evaporates at the edges. The same effect can be seen with the DIC Fluidics arrangement, and the field can also be moved around to inspect different areas by sliding the flexible film extension 11, bonded to the cover sheets 12 and 16, against the film surface 9, typically using apposed thumbs in areas A and B to a selected position over the micro optic 1.

[0125] However, if one side of the coversheet assembly is preferentially pressed by the right thumb in area B for example, area B gets an increase in pressure gradient compared to area A. This acts on the plasma layer through the small deflection of the cover sheet 16, and this pressure area B becomes unbalanced and plasma will flow from this higher pressure area to a lower pressure area. This is indicated by the arrows 33, the red blood cells are accelerated with the plasma through most of the channels / gaps 35 to 36. This gives a new controllable dynamic to the movement of the red blood cells and they can demonstrate extraordinary acceleration and velocity when encountering obstacles or restrictions. This demonstrates the dynamic of healthy blood cells being able to change size and shape to flow through veins and capillaries much smaller than their free form dimensions.

[0126] In the example shown in Figure 7, the microstructure 15 restrict the flow of the plasma to the gaps or channels in microstructure 15. The channels / gaps are gradually stepped in size to show the change of velocity of the red blood cells. The size changes are very small in the order of one or two microns. The design of the microstructure can be standardised to show specific characteristics. Specifically, the viscosity can indicate a tendency towards blood clotting and rouleaux at different temperatures and blood cell count. The red blood cell flow through the gaps or channels shown as 35 and 36 are markedly different, than through channel / gap 37 which indicates it is too small for the blood cells to pass through. Plasma has around one third of the density of red blood cells and the viscosity is much lower and so it can pass through all the channels / gaps more easily, but the red blood cells get deflected away from a slot that is too narrow to allow it to pass through. As the pressure gradient in the plasma equalises from side to side the flow slows to a stop.

[0127] Figure 8 shows that if the area A is then preferentially pressed on the other side the flow is dramatically reversed and the plasma and red blood cells instantly accelerate in the opposite direction. Figure 8 also indicates a different microstructure in use, being the lower right hand group of micro structures rather than the centre group in Figure 7.

[0128] Figures 9a and 9b show further detail of the microstructure which in this example is 0.20mm (s) in height and 18mm (t) in width which fills the phone screen from side to side 21 and at 300x optical magnification that appears as 60mm (u) in height on screen.

[0129] Figures 10a and 10b show an example of a microfluidic device or microstructure of the present invention a= 0.07mm, b= 0.004mm, c=0.005mm, d= 0.006mm e= 0.007mm, f = 0.008mm, g = 0.035mm, h = 0.24mm and j = 0.006mm. The height of the gap between the base sheet 12 and the top cover sheet 16 is a little larger than the flat dimension of the doughnut form of a red blood cell at around 6 microns. The system is similar to known capillary microfluidics, micro channels and micro fluidic networks / capillaric circuits, the methods of production of the micro structures are similar and well understood. Mass production of these microstructures can be achieved at low cost using 2 photon grayscale lithography to produce a nickel master for UV printing or embossing.

[0130] Generally the red blood cells can elongate and travel along smaller capillaries with a diameter of around 5 microns or less. The capillaries can also expand and contract and hydrophilic structured energy enables slow continuous flow in the smallest of capillaries to allow the exchange of gases and nutriments and to remove residues. Because the micro structures are rigid and not as slippery as the capillaries they impart a greater impedance to flow for the same size. Figures 11a shows an alternative and more complex layouts of a microfluidic device or microstructure to give more insight to the nature of the flow characteristics and the impact of cell shear on viscosity as blood is non newtonian.

[0131] Figures 12a and 12b shows a further alternative embodiment of microstructure arrangement or microfluidic device 40, which acts as a circular capture device shown from the front that can be filled completely with red blood cells 22. The microstructure arrangement 40, acts as a cage, as the plasma flow 33 moves the red blood cells through the large opening item 49. White blood cells are prevented from movement as the plasma gap height between plates 12, 16 is around 6 microns which is smaller than white blood cells which are generally larger than 10 microns. The plasma can easily pass through the 7 radial gaps / channels 48 but the gaps are too small for the transition of the red blood cells. The inward flow of blood cells continues until there is no space left. A repeatable cell count can then be performed using the smartphone app. The microstructure 40, can be emptied of all red blood cells by reversing the plasma flow 33 as explained by Figures 7 and 8.

[0132] Figure 12b shows how a sample of the red blood cells can be accessed via the addition of a small through hole or aperture 47 in the correct position to align with the microstructure arrangement or capture device 40, together with typically a gas permeable PU adhesive film 46 bonded to the underside of the cover sheet item 16. When a sample of red blood cells are positioned in the microstructure capture device item 40 a solution 45 can be added to the top surface of the cover sheet item 16. The solution 45 will come into contact with the permeable membrane item 46 through the hole item 47. Chlorine dioxide gas from CDS solution 45 for example, will permeate the membrane and oxygenate the red blood cells held in confinement by the micro structure capture device 40. Venus blood taken from finger tip sample are usually lower in oxygen content and they very quickly respond to this intervention and take up oxygen and become enlarged. This change in density can be related to the available haemoglobin. Other fluids such as structured water can also be used experimentally to determine effect on mitochondria and cell activity.

[0133] Figure 13, shows a further alternative microstructure arrangement which is incorporated on a cover glass slip to indicate blood vitality. The blood viscosity and flow rely on a complex mixture of factors which are influenced by many things so variations in readings will require careful analysis to draw any conclusions. However, blood dynamics are a very useful indicator of change. Sialylated glycoproteins of the red blood cell (RBC) membrane are responsible for a negatively charged surface which creates a repulsive electric zeta potential. If this charge is reduced, the blood cells tend to clump and form rouleaux and increases the erythrocyte sedimentation rate (ESR). The pressure exerted on the plasma by finger pressure on the cover glass will be indicated by the speed of plasma carrying the red blood cells through the microstructure. Red blood cell are directed towards the inlet indicated by the arrow 33. If, for example, the red blood cells emanating from the first and largest of the exit channels is kept at a visible and discernible rate rather than a blur of red blood cells - due to low shutter rate of the camera - in the channel and at the exit point, the pressure can be regulated and be repeatable. The channels are smaller and more restrictive as the marked numbers by each channel increases. With practice the maximum number of the channel where the flow has effectively stopped can be recorded. This is shown in this example by channel 6 indicated by 48.

[0134] Figure 14, shows a further alternative microstructure 15 with 19 channel sections with a central channel in each section shown as item 48, with smaller channels to each side of the central channel reducing in size. Continual flow in the direction of arrow 33 will entrap damaged cells and debris that cannot flow with the plasma through all the channels available.

[0135] Figure 15a, shows the optical arrangement when the stepped retaining disc assembly 4, is mounted on the screen 7, of a smart phone such that the optic or lens 1, aligns with an imaging device such as the front camera lens 5. The cover slide 16, is separated from the optic 1, by an air gap in the order of approximately 5pm to 15pm, which created by the films 6 and 9 sitting proud of the lens 1. Light from a specially configured light source rays SI pass through a flexible film extension 11, and through the coversheet 16, through the sample area 19, and through the coversheet 12 and enter the optic 1 undergoes total internal reflection 2. The light is specially configured to have a diffuse emitting area of about 1 to about 1.5 square millimetres and emits light at about 3000k to about 4000K while consuming a current of in the range of about 5pA to about 25pA. In this embodiment, the light source has a diffuse emitting area of about 1.1 square millimetres and emits light at about 3800k while consuming a current of about 13pA.

[0136] The outer rays of SI enter the optic 1 and are totally internally reflected and develop a strong surface energy where some of these light energy rays 17 and 18, are reflected back towards the sample area 19. This light undergoes a phase change due to the total internal reflection and the phase change induces a destructive wave interference with SI. The combination of configured light source rays SI and reflected interference rays are described here as Emission Interference Contrast (EIC), operating in the same way as Differential Interference Contrast (DIC) but instead of using an additional and separate out of phase light source with both rays in a common transmission mode, the optic 1, emits destructive out of phase interference waveforms reflected back towards the source to produce positive phase contrast. The result are rays SI and S2 combining to provide DIC like positive contrast.

[0137] Figure 15b, shows the outer rays SI are configured to be convergent from a localised light source rather than parallel from a distant source. This has a profound effect on the control of the contrast characteristics as will be later described.

[0138] Figure 16a shows an example of the screen image obtained on a smart phone with no blood sample assembly items 11, 16 and 12 in place. The light source passes through the optic or lens 1 and is recorded by the digital imaging device or camera 5, through the screen glass 7 (not shown). The optic item 1, shows extreme luminescence at a surface of the lens 23, and there is an outer region 17, which displays photonic nano-jets against the dark background of the lens holding insert 4 (see Figure 16b), this indicates high Total Internal Reflection (TIR) energy which escapes at the surface at different frequencies due to the different travel lengths within the optic. The TIR is maintained by using an opaque dark insert retaining disc 4, which blocks light escaping at the contact circle. If the optic insert or retaining disc 4, is replaced using a clear material, the light energy is released and there is no excess energy at the surface of the optic or lens 1.

[0139] Dust particles 26, show strong contrast halos 27, when viewed from different angles and these are seen on both front and back surfaces of the optic at the same time using a coherent light source. These artefacts all but disappear when a controlled light source is used. The light source has to be configured to produce a non-coherent diffused light from a suitable local source, for example a suitable LED at low power as described herein.

[0140] Figure 17, shows the light energy available at the surface of the optic 1, the coversheet 12, is put in contact with the optic 1, and an intense halo of light 23, is observed. The halo diminishes in size as a very small gap between the optic and coversheet is introduced and disappears within a few microns of movement.

[0141] It is understood that the excess light energy escapes the optic or lens 1 and is partly reflected back towards the light source as possibly evanescent wave forms with varying phase timing providing positive phase contrast through destructive interference. This gives an enormous advantage as the system is single sided and does not require complex transmission through the optic set, as required by normal DIC systems. As a consequence, the system is extraordinarily compact and inexpensive compared to conventional DIC.

[0142] The system lends itself particularly well towards more complex forms of biological analysis particularly that of Optical Pattern Recognition Imaging and Fluidics. The requirement to have a range of complex optical sensor heads to read the many aspects of dynamic flow biology, brings the ability to miniaturise the equipment required to a small desktop device.

[0143] For example, in figure 3 there is an example of five microstructures spaced on a base sheet item 12, of quartz glass. Each of the microstructures can be designed to show different characteristics each with its own with optical channel and camera for simplicity and fast throughput. The cover sheet item 16 can be modulated with three or more pressure actuators with feedback sensors to cause plasma flow in any direction and velocity to suit the requirements of the micro structures. An important feature of each of the microstructures is that it’s height locally controls the plasma thickness between the two flexible quartz glass sheets so that consistent flow occurs over the structure while the surrounding plasma thickness is modulated to provide dynamic movement of the plasma and blood cells of interest. The flow direction is alternated such that an external flow reservoir is not required. The estimated 600 million blood cells in one drop or lOpL of blood is sufficient for statistical analysis.

[0144] Pattern Recognition Imaging and Fluidics can also be used to detect and identify smaller particles of particular interest such as micro blood clots which are sometimes not detected by standard blood tests like D-Dimer other than more specialised pathology laboratories using Imaging Flow Cytometry (IFC) which has been used for detecting microclots in individuals suffering from both Long COVID and other conditions with similar pathology, such as myalgic encephalomyelitis. Figure 18, shows the arrangement detailed in Figure 15a and 15b but with a controlled light source in the form of an adjacent LED 56. The distance shown as dimension ‘F ’can be varied by adjusting the mount pin 62. External light is shielded using an enclosed elongated structure, referred to as a light bar 60, which holds the LED 56, in position over the centre line of the micro optic or lens 1. The effective area of the light source diameter E and hence the convergent angle can be varied by distance ‘F ’and the area of the light emitting surface of 56. Tests were conducted where dimension ‘F ’was between 1mm and 1050mm and the diffuse emitting surface was between 1 square mm at lOpW, and 300mm diameter or 70,000 square mm at 10W (800Lm). The extremes gave similar characteristics of interference contrast. The similar convergent angle was around 14 deg in this arrangement. Obviously, a shorter distance ‘F ’was preferred and at 3.5mm with an emitting area of around 1.5 square mm and using 15pW resulted in an extremely efficient and compact lighting regime. At 15pW the current was 6pA and projected battery life with 25mAh capacity was 4000h. With a daily 2 hour operation the battery life would be 5 years. Alternatively about 50,000 5 minute screenings.

[0145] Figure 19, shows the construction of the light bar 60. The LED 56, is connected via a flex film printed circuit 66 or by individual strands of coated copper wire 0.12mm diameter, as shown. Two 25mAh 1.55v silver oxide batteries type 364, 72, in series can be used, and these are switched using an ultra miniature SMT tactile push button switch 71, this is operated by a push cross pin 69, with an off-centre radial detent to allow the off position at one extreme position and an on position at the other extreme position. The light bar 60 is pivoted about a cross pin hole 70. A SMT resistor 73, can be used to limit the current to around 5pA giving a 5000h run time. A transparent window 68 is used to indicate the light on mode. The batteries could be user replaceable as the two halves can be held together at the LED end by two bonded disc magnets which also hold the light bar in contact with the cover glass slips against the film 9 of housing 3 of the microscope apparatus of the present invention. However, the extraordinary life of the batteries make replacing them unnecessary as the Light bar would be easier to replace or exchange in the long term. The position of the light bar 60 and support block 75 (shown in Figure 22) allow full access to use thumbs to accurately adjust the position of the blood sample held between the coversheets 12 and 16 using the support film 11. The thumbs operate in the areas indicated by items A B and the surface of the DIC microscope item 3, has a low friction non-marking film 9 to allow a non-stick smooth action (as shown in Figure 8).

[0146] No external light is required for the blood examination and can be conducted in low light or complete darkness. For use, the internal lighting is switched on using the cross pin switch 69, mounted in the light bar 60. The light bar is pivoted over a small angle via a cross pin in the support block or mount block 75. The light bar 60 pivots onto and magnetically holds the cover glass slips 12 and 16 in position against the film 9 of the steel plate 3, and the camera lens of the smart phone or recording device.

[0147] Figure 20a, shows a further embodiment of the present invention with a drive wire stage for accurate mapping and recording locations and areas using the microscope apparatus of the present invention (Micro Lab App). This embodiment of the present invention is provided with a removable top cover 80 allowing access to the stage frame 84, that holds the sample slide / cover glass assembly 12, 16. The control wheels 81 allow the sample slide to be moved in an X-Y direction to ensure that the area of the sample (not shown) that is to be viewed is placed under light bar 60. This embodiment is provided with a USB-C charging and communication port 83 and on / off switch 82, which are in communication with the base unit 83 which houses the battery and electronics. An optional two channel motor drive (not shown) allows third party / health provider remote operation of the device for qualification and or second opinion / advice.

[0148] Figures 20b shows a top cover 180 which a sample slide 12,16 in place under light bar 60. This embodiment of the invention uses electronic means to move around the stage frame (not shown) and, therefore, there are blanks 181 instead of control wheels (as shown in Figure 20a).

[0149] Figure 20c shows the stage frame 84 removed from top cover(not shown). Accordingly, the control wheels 81 which move the guide frames 85, 87 can clearly be viewed. By twisting the control wheels 81 the guide frame 85 can be moved along the x and / or y axis, which allows any sample on a sample slide (not shown) to be positioned under the light bar 60. Figures 21a, 21b and 21c shows the construction of the stage frame 84 that holds the guide frames 85 and 87 which can be moved by the wire 86, 89, pivot pin 90, control wheel 81 and springs 88 arrangements. The springs 88 are such that only a light tension is applied to the wires 86, 89 such that lateral movement is minimised. Rotation of the control wheels 81 effects movement of the wires 86 and 89 which then move the guide frames 85 and 87.

[0150] Figure 22, shows the DIC Fluidics device item 3, mounted on a smart phone 20.

[0151] The invention teaches a method of construction and use of a medical device to enable self monitoring of live blood analysis using Differential Interference Contrast (DIC) imaging and enable users to simply use the device on a smart phone with an optional phone app if desired. Conventional live blood analysis use dark field microscopes that show a relative stationary image field of the plasma with red and white blood cells, whereas Differential Fluidics introduces a pressure gradient within the plasma strata that gives an added dimension of the movement arrow 33 of the red blood cells 25. They can demonstrate dynamic deformation and velocity change when encountering obstacles such as the white blood cells 95 or air bubbles that remain stationary as their larger size causes be them to be held still by the cover glass. The obstacles are specifically designed using micro structures such that a lack of vitality of red blood cells from high viscosity for example, can indicate a tendency towards agglutination and rouleaux that can be quantified against ESR. The micro structures can also collect and contain specific sample sizes to allow accurate size and cell count and can also be used for introducing gas / fluid media for advanced diagnostics such as zeta potential and haemoglobin Hb.

Claims

Claims1. A microscope apparatus comprising a housing for a lens and a lens, wherein the housing for the lens has a camera facing surface and a light source facing surface, wherein the lens has a light source facing surface and wherein the light source facing surface of the lens is recessed from the light source facing surface by in the range of about 5pm to about 15pm.

2. A microscope apparatus according to claim 1, the apparatus further comprising a light source.

3. A microscope apparatus according to claim 2 wherein the light source is configured to face towards the light source facing surface of the housing and an emitting area of the light source provides a convergent beam angle in the range of about 6 degrees to about 22 degrees.

4. A microscope apparatus comprising a housing for a lens, a lens and a light source, wherein the housing for the lens has a camera facing surface and a light source facing surface, wherein the lens has a light source facing surface and wherein the light source is configured to face towards the light source facing surface of the housing and an emitting area of the light source provides a convergent beam angle in the range of about 6 degrees to about 22 degrees.

5. A microscope apparatus according to claim 4, wherein the light source facing surface of the lens is recessed from the light source facing surface by in the range of about 5pm to about 15pm.

6. A microscope apparatus according to any preceding claim wherein the light source facing surface of the lens is recessed from the light source facing surface by in the range of about 7pm to about 13pm.

7. A microscope apparatus according to any preceding claim wherein the light source facing surface of the lens is recessed from the light source facing surface by about 10pm.

8. A microscope apparatus according to any of claims 2 to 7 wherein the light source is configured to face towards the light source facing surface of the housing and an emitting areaof the light source provides a convergent beam angle in the range of about 10 degrees to about 18 degrees.

9. A microscope apparatus according to any of claims 2 to 8 wherein the light source is configured to face towards the light source facing surface of the housing and an emitting area of the light source provides a convergent beam angle about 14 degrees.

10. A microscope apparatus according to any of claims 2 to 9 wherein a light emitted from the light source is contained and directed towards the lens.

11. A microscope apparatus according to any of claims 2 to 10 wherein the light source is an LED.

12. A microscope apparatus according to any of claims 2 to 11 wherein the light source has a diffuse emitting area of about 1 to about 1.5 square millimetres and emits light at about 3000k to about 4000K while consuming a current of in the range of about 5pA to about 25pA.

13. A microscope apparatus according to claim 12 wherein the light source has a diffuse emitting area of about 1 to about 1.5 square millimetres and emits light at about 3000k to about 4000K while consuming a current of in the range of about lOpA to about 15pA.

14. A microscope apparatus according to either claim 12 or 13 wherein the light source has a diffuse emitting area of about 1.1 square millimetres and emits light at about 3800k while consuming a current of about 13pA.

15. A microscope apparatus according to any preceding claim wherein the lens is a micro- spherical ball lens.

16. A microscope apparatus according to any preceding claim wherein at least part of a surface of the housing adjacent the lens is opaque and / or reflective.

17. A microscope apparatus according to any preceding claim wherein the microscope apparatus further comprising a retaining means.

18. A microscope apparatus according to claim 17 wherein the retaining means allows for releasable coupling.

19. A microscope apparatus according to either claim 17 or 18 wherein the retaining means retains, in use, a sample slide and / or, when dependent upon claims 2 to 16, the light source.

20. A microscope apparatus according to claim 19 wherein the sample slide is a pair of glass slips.

21. A microscope apparatus according to any of claims 17 to 20 when dependent upon claims 2 to 16 wherein the light source comprises the retaining means.

22. A microscope apparatus according to any of claims 17 to 21 wherein the retaining means is a magnet.

23. A microscope apparatus according to any preceding claim wherein the housing is at least partly formed from a magnetic substance.

24. A microscope apparatus according to any preceding claim wherein the camera facing surface of the housing comprises a securing means.

25. A microscope apparatus according to any preceding claim wherein the securing means allows for releasable coupling.

26. A microscope apparatus according to any preceding claim wherein the securing means comprises a tacky film.

27. A microscope apparatus according to claim 26 wherein the tacky film at least partly covers the camera facing surface of the housing for the lens.

28. A microscope apparatus according to any of claims 19 to 27 wherein the sample slide further comprises a microfluidic device.

29. A microscope apparatus according to any preceding claim wherein the housing further comprises movement means for, in use, moving the sample slide.

30. A microscope apparatus according to claim 29 wherein the movement means affords movement of the sample slide in an x and / or y axis in a horizontal plane.

31. A microscope apparatus according to any preceding claim wherein the microscope apparatus is configured to be used with a digital imaging device.

32. A microscope apparatus according to claim 31 wherein the digital imaging device is a handheld device.

33. A microscope apparatus according to either claim 31 or 32 wherein the digital imaging device is a camera in a mobile telephone.

34. A method of using a microscope apparatus according to any of claims 1 to 33, the method comprising: a) placing a sample of bodily fluid on a sample slide; b) placing the camera facing surface of the housing for the lens of the microscope apparatus according to any of claims 1 to 33 in cooperative alignment with a digital imaging device; c) placing the sample slide on the light source facing surface of the housing for the lens of the microscope apparatus according to any of claims 1 to 33; d) applying light to the sample slide from a light source; and e) optionally, capturing the image displayed on the digital imaging device.

35. A method of using a microscope apparatus according to any of claims 1 to 33 or the method according to claim 34, the method comprising of a microfluidic device being operated by finger / thumb pressure to: a) position the microfluidic device accurately with the imaging device; and b) initiate dynamic plasma flow and red blood cell movement in any desired direction and speed.

36. A method of using a microscope apparatus according to any of claims 1 to 33 or the method according to either claim 34 or 35, the methodcomprising of a microfluidic device being operated by suitable electrical actuators to a) position the microfluidic device accurately with the imaging device; and b) initiate dynamic plasma flow and red blood cell movement in any desired direction and speed.

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